Search PubMed⌕ Search

Biomedical subjects

J Xie

Publications and source records attributed to J Xie.

At least 55 records · Page 3Linked to original sources

Par-4 is a synaptic protein that regulates neurite outgrowth by altering calcium homeostasis and transcription factor AP-1 activation.

Although Par-4 (prostate apoptosis response-4) is involved in initiation of neurodegenerative cascades associated with certain neurodegenerative disorders, normal physiological roles of Par-4 in neurons have remained elusive. It was recently reported that Par-4 protein levels could be regulated at translational level in synaptic terminals following apoptotic insults, suggesting that Par-4 might play a role in synaptic function. We report that Par-4 is a synaptic protein preferably localized in postsynaptic density (PSD). The expression of Par-4 in synaptosome preparations and PSDs are developmentally and regionally regulated. Synaptic Par-4 is enriched in the cerebral cortex and the hippocampus, but not in the cerebellum. In vitro as well as in vivo experiments demonstrate that the levels of synaptic Par-4 increase as the neurons mature. Overexpression of Par-4 in transfected PC12 cells inhibits nerve growth factor (NGF)-induced cellular differentiation and neurite outgrowth by a mechanism involving aberrant elevation of intracellular calcium levels and suppression of activation of the transcription factor AP-1. The actions of Par-4 were consistently blocked by co-expression of the dominant negative regulator of Par-4 activity (the leucine zipper domain of Par-4). Since the leucine zipper domain of Par-4 (Leu.zip) may mediate protein--protein interactions, the results indicate that the actions of Par-4 require its interaction with other protein(s) or dimerization with itself. These results suggest that Par-4 may play an important role in postsynaptic signal transduction and regulation of cellular pathways associated with cellular differentiation and neurite outgrowth. Identification of Par-4 as a novel synaptic protein may have significant implications in understanding the mechanisms of synaptic functions in physiological and pathological settings.

Animals↗

Energy transfer cassettes for facile labeling of sequencing and PCR primers.

Fluorescence energy transfer (ET) primers and terminators are the reagents of choice for multiplex DNA sequencing and analysis. We present here the design, synthesis and evaluation of a four-color set of ET cassettes, fluorescent labeling reagents that can be quantitatively coupled to a thiol-activated target through a disulfide exchange reaction. The ET cassette consists of a sugar-phosphate spacer with a FAM donor at the 3'-end, an acceptor linked to a modified T-base at the 5'-end of the spacer and a mixed disulfide for coupling to a thiol at the 5'-end. The acceptor dye emission intensities of ET labeled primers produced in this manner are comparable to commercial ET primers. The utility of our ET cassette-labeled primers is demonstrated by performing four-color capillary electrophoresis sequencing with the M13(-21)forward primer and by generating and analyzing a set of single-nucleotide-polymorphism-specific PCR amplicons.

Chromatography, High Pressure Liquid↗

A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels.

Calcium regulation of gene expression is critical for the long-lasting activity-dependent changes in cellular electrical properties that underlie important physiological functions such as learning and memory. Cellular electrical properties are diversified through the extensive alternative splicing of ion channel pre-messenger RNAs; however, the regulation of splicing by cell signalling pathways has not been well explored. Here we show that depolarization of GH3 pituitary cells represses splicing of the STREX exon in BK potassium channel transcripts through the action of Ca2+/calmodulin-dependent protein kinases (CaMKs). Overexpressing constitutively active CaMK IV, but not CaMK I or II, specifically decreases STREX inclusion in the mRNA. This decrease is prevented by mutations in particular RNA repressor sequences. Transferring 54 nucleotides from the 3' splice site upstream of STREX to a heterologous gene is sufficient to confer CaMK IV repression on an otherwise constitutive exon. These experiments define a CaMK IV-responsive RNA element (CaRRE), which mediates the alternative splicing of ion channel pre-mRNAs. The CaRRE presents a unique molecular target for inducing long-term adaptive changes in cellular electrical properties. It also provides a model system for dissecting the effect of signal transduction pathways on alternative splicing.

Alternative Splicing↗

Temperature-induced decoupling of phycobilisomes from reaction centers.

Temperature-induced decoupling of phycobilisomes (PBSs) from the reaction centers in the PBS-thylakoid membrane complexes was observed at 0 degrees C. The fluorescence yields of photosystem (PS) I and PSII decreased and that of PBSs increased with selective excitation of PBSs at 0 degrees C, while the yield of PBSs decreased and those of the two photosystems increased with selective excitation of chlorophyll a at room temperature (RT). It indicated that the decoupling of PBSs from the two photosystems led to changes of energy transfer efficiencies, which can be explained by partial detachment of PBSs from thylakoid membrane. The temperature-dependent processes were reversible, i.e. with temperature going up to RT, the complexes could restore to the functionally coupled state with a time constant about 30 s. Based on these results, it could be deduced that PBSs should be in parallel connection with the two photosystems.

Betaine↗

Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway.

Prostate apoptosis response-4 (Par-4) is a leucine zipper protein that promotes neuronal cell death in Alzheimer's disease (AD). Neuronal degeneration in AD may result from extracellular accumulation of amyloid beta peptide (Abeta) 1-42. To examine the effect of Par-4 on Abeta secretion and to reconcile amyloid/apoptosis hypotheses of AD, we generated IMR-32 cell lines that overexpress Par-4 and/or its leucine zipper domain. Overexpression of Par-4 did not significantly affect levels of the endogenously expressed beta amyloid precursor protein but drastically increased the Abeta(1-42)/Abeta(total) ratio in the conditioned media about 6-8 h after trophic factor withdrawal. Time course analysis of caspase activation reveals that Par-4 overexpression exacerbated caspase activation, which is detectable within 2 h after trophic factor withdrawal. Furthermore, inhibition of caspase activity by the broad spectrum caspase inhibitor BD-fmk significantly attenuated the Par-4-induced increase in Abeta 1-42 production. In addition, the effects of Par-4 on secretion of Abeta 1-42 were consistently blocked by co-expression of the leucine zipper domain, indicating that the effect of Par-4 on Abeta secretion may require its interaction with other protein(s). These results suggest that Par-4 increases secretion of Abeta 1-42 largely through a caspase-dependent pathway after apoptotic cascades are initiated.

Amyloid beta-Peptides↗

Defective Fas ligand-mediated apoptosis predisposes to development of a chronic erosive arthritis subsequent to Mycoplasma pulmonis infection.

OBJECTIVE: To determine whether defective T cell apoptosis is associated with the development of a chronic arthritis subsequent to mycoplasma infection, and to determine whether deletion of T cells can prevent the development of this arthritis. METHODS: B6 wild-type (B6-+/+), B6-lpr/lpr, and B6-gld/gld mice were infected with Mycoplasma pulmonis. The severity of lymphocytic infiltration and joint damage was evaluated, and the degree of recovery of viable mycoplasma from the spleen and joints was determined. Antigen-presenting cells derived from Fas mutant lpr mice (lpr-APC) were transfected ex vivo with an adenovirus (Ad) vector to yield lpr-APC expressing high levels of Fas ligand (lpr-APC-AdFasL), which in turn were transferred intraperitoneally into M pulmonis-infected B6-gld/gld mice. The development of arthritis subsequent to M pulmonis infection and the induction of apoptosis of cells within the synovial tissue and lymph nodes of lpr-APC-AdFasL-treated B6-gld/gld mice were determined. RESULTS: Infection of B6-lpr/lpr and B6-gld/gld mice with M pulmonis resulted in an acute-phase inflammation of the synovium that later developed into a chronic erosive arthritis. Similar infection of B6-+/+ mice resulted only in an acute joint inflammatory response that resolved. Chronic arthritis in B6-gld/gld mice and B6-lpr/lpr was not due to persistent infection, since there were no differences in the rates of clearance of M pulmonis from the joints of B6-gld/gld or B6-lpr/lpr mice compared with B6-+/+ mice. Treatment of infected B6-gld/gld mice with lpr-APC-AdFasL resulted in a significantly decreased incidence of chronic arthritis that was associated with a decrease in lymph node T cells, but not with apoptosis of synovial T cells or fibroblasts. CONCLUSION: Defective Fas/FasL-mediated apoptosis of T cells is an important factor that rendered arthritis-resistant B6 mice susceptible to the development of a chronic erosive arthritis subsequent to mycoplasma infection. In vivo lpr-APC-AdFasL cell-gene therapy is a safe and effective method for inhibiting the development of this arthritis.

Acute Disease↗

Effect of bilateral subthalamic nucleus stimulation on parkinsonian gait.

Clinical reports show that bilateral subthalamic nucleus (STN) stimulation is effective in improving parkinsonian gait. Quantitative analysis of the efficacy of STN stimulation on gait is of interest and can be carried out using a commercially available stride analyser. Ten parkinsonian patients (5 men, 5 women) with a mean age of 55.8, SD 9.6 years were included in our study. They had a mean duration of Parkinson's disease (PD) of 13.3, SD 4.5 years and a motor examination score (part III of the Unified Parkinson's Disease Rating Scale) (UPDRS) of 43, SD 13 in off-stimulation off-drug condition. All the patients had bilateral chronic STN stimulation which had started from 3 to 36 months before the study. Patients were evaluated in off-drug and on-drug conditions both with and without stimulation. We analysed the principal gait measures: velocity, cadence, stride length, gait cycle, duration of single and double limb support. The clinical parkinsonian signs were evaluated with the part III of the UPDRS. In the off-drug condition, STN stimulation significantly (p < 0.05) improved velocity and stride length. The effect was similar to that of levodopa. When STN stimulation was switched on at the best of the levodopa induced effect, no further improvement was observed. The UPDRS motor score was significantly (p < 0.001) decreased after both stimulation and levodopa. In conclusion, STN stimulation is effective on parkinsonian gait.

Adult↗

Deep brain stimulation in the treatment of severe dystonia.

A retrospective study of a consecutive series of 19 patients with medically intractable dystonia treated with uni- or bilateral deep brain stimulation (DBS) is reported. A minimal follow-up of 6 months was available, up to eleven years in one patient. The first twelve consecutive patients (4 with primary and 8 with secondary dystonia) were treated with chronic stimulation of the posterior part of the ventrolateral thalamic nucleus (VLp). In this group global functional outcome was improved in 8 patients, although dystonia movement and disability scale scores did not show significant improvement. Of the 12 patients treated first by VLp DBS, three (1 primary and 2 secondary dystonia) underwent pallidal (GPi) DBS after the VLp DBS failed to improve their symptoms. The last seven consecutive patients (5 primary and 2 secondary dystonia) were treated directly with GPi DBS. Extracranial infection prevented chronic GPi DBS in one patient. In another GPi patient, preliminary negative tests with the electrodes discouraged implantation of the stimulators, and the patient was not treated with chronic DBS. In the remaining group of eight patients including those previously treated with VLp DBS, chronic GPi DBS resulted in a significant improvement in the dystonia movement scale and disability scores. Although this is a retrospective study dealing with dystonia of heterogeneous etiology, the results strongly suggest that GPi DBS has a better outcome than VLp DBS.

Adolescent↗

Qian-Kun-Nin, a Chinese herbal medicine formulation, attenuates mitochondrial oxidant stress in cardiomyocytes.

Qian-Kun-Nin is a Chinese herbal medicine formulation used for several indications, including the treatment of cardiovascular diseases. This formulation contains herbs which possess antioxidant properties. In this study, Qian-Kun-Nin's ability to confer protection to cardiomyocytes against reactive oxygen species (ROS) generated during mitochondrial electron transport inhibition was tested. The intracellular fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH-DA, sensitive to H(2)O(2) and hydroxyl radicals) was used to assess intracellular ROS, and propidium iodide (PI) was used to assess viability in cultured chick embryonic cardiomyocytes. Qian-Kun-Nin significantly attenuated oxidation of DCFH in cells exposed to the mitochondrial site III inhibitor, antimycin A, consistent with a decrease in oxidative stress. These attenuated oxidant levels were associated with improved cell survival. After antimycin A exposure, Qian-Kun-Nin decreased cell death from 51. 6+/-3.3% in untreated cells to 27.3+/-3.8% in treated cells at 2 h. We conclude that Qian-Kun-Nin attenuates oxidant stress and protects cells from lethal oxidant damage during mitochondrial electron transport inhibition, and thus its therapeutic potential in treating cardiovascular diseases may relate to its antioxidant properties.

Analysis of Variance↗

A placebo controlled evaluation of the antifibrillatory effects of carvedilol.

This article evaluates the antifibrillatory effects of carvedilol 5 mg/kg and vehicle (dimethyl-formamide) over time. Sprague-Dawley rats were anesthetized and intubated. They underwent baseline ventricular fibrillation threshold (VFT) determination and then received 1 of the 2 treatments (n = 10/group) over 8 minutes. VFT and determinations were performed at 2, 7, 15, 30, 45, and 60 minutes postinfusion. Carvedilol significantly increased the VFT at 2, 7, 15, 30 minutes versus baseline and the vehicle control group. Carvedilol significantly reduced the heart rate and the mean arterial pressure at every evaluable time point versus baseline and vehicle control. Carvedilol showed significant antifibrillatory effects versus baseline and vehicle for the first 30 minutes but not thereafter, even though the heart rate and mean arterial pressure remain significantly reduced.

Adrenergic beta-Antagonists↗

The effect of lumbar sympathectomy in the spinal nerve ligation model of neuropathic pain.

To evaluate the sympathetic dependency of pain behaviors in an animal model of neuropathic pain, the effect of surgical sympathectomy on the mechanical sensitivity of the hindpaw was examined in rats with L5 spinal nerve ligation. Mechanical sensitivity was determined by measuring foot withdrawal thresholds to mechanical stimulation with von Frey filaments applied to the base of the third or fourth toe. Tight ligation of the segmental L5 spinal nerve led to the development of mechanical hypersensitivity in the hindpaw. The effects of 2 different procedures of surgical lumbar sympathectomy on mechanical hypersensitivity were compared, limited (resection of sympathetic chain/ganglia L2 to L4 segments) and extensive (resection of L2 to L6 segments) sympathectomies. Mechanical hypersensitivity produced by L5 spinal nerve ligation was partially but significantly reduced by both sympathectomy procedures. In a separate group of rats, the L5 spinal nerve was ligated while irritating the neighboring L4 spinal nerve. This procedure produced a lesser degree of mechanical hypersensitivity, and subsequent sympathectomy had no effect on these animals. These data suggest that sympathectomy is effective in this model only when the animals show severe mechanical hypersensitivity.

Journal Article↗

Effect of bilateral subthalamic nucleus stimulation on gait in Parkinson's disease.

The fundamental disturbance of the parkinsonian gait is the reduction in walking velocity. This is mainly due to reduction in stride length, while cadence (steps/min) is slightly enhanced. Treatment with L-dopa increases stride length while cadence is unchanged. Chronic stimulation of the thalamus has no effect on Parkinsonian gait. The efficacy of electrical stimulation of the subthalamic nucleus (STN) on gait in advanced Parkinson's disease has been clearly demonstrated clinically. The aim of the present study was to quantify the changes in gait measures induced by STN stimulation and L-dopa and to assess possible differential or additive effects. Eight Parkinson's disease patients (mean +/- SD age 48.1 +/- 7.3 years) with chronic bilateral STN stimulation (mean duration of disease 13.3 +/- 2.4 years, mean stimulation time 15.4 +/- 10.6 months) and 12 age-matched controls were investigated. Subjects walked on a special treadmill with a closed-loop ultrasound control system that used the subject's position to adjust treadmill speed continuously for the actual walking velocity. In an appropriate crossover design, spatiotemporal gait measures and leg joint angle movements were assessed for at least 120 stride cycles in four treatment conditions: with and without stimulation and with and without a suprathreshold dose of L-dopa. With STN stimulation, there were increases of almost threefold in mean walking velocity (from 0.35 to 0.96 m/s) and stride length (from 0.34 to 0.99 m). Cadence remained constant. The range of motion of the major leg joints also increased. L-Dopa alone had a slightly weaker effect, with an increase in walking velocity to 0.94 m/s and in stride length to 0.92 m at a similar cadence. These increased values were in the range of those for healthy age-matched subjects performing the same task. The combination of both treatments further increased the mean walking velocity to 1.19 m/s and stride length to 1.20 m at an unchanged cadence. However, not all patients receiving STN stimulation improved further when they also received L-dopa. These results demonstrate that chronic bilateral STN stimulation, like treatment with L-dopa, improves walking velocity by increasing stride length without changing cadence. STN stimulation almost exclusively affects mechanisms involved in the control of spatial gait measures rather than rhythmicity. The gait measures obtained with STN stimulation alone are in the range of control subjects.

Adult↗

1,6-Asymmetric induction during the conjugate addition of arylcopper reagents to a chiral sulfinyl-substituted pyrrolyl alpha,beta-unsaturated amide.

The asymmetric conjugate addition of arylcopper reagents derived from aryl Grignard reagents and copper(I) iodide to a chiral 1-[2-(p-tolylsulfinyl)]pyrrolyl cinnamide proceeded smoothly to give (3R)-adducts with high diastereoselectivities (> or =92% de) in high yields. Conjugate additions either of the cinnamide with the alkyl Grignard reagent-copper(l) iodide combination or of the crotonamide derivative with aryl Grignard reagent-copper(l) iodide gave moderate to good diastereoselectivities. With these sulfinyl pyrrolyl alpha,beta-unsaturated amides, the chiral auxiliary was efficiently recovered without any loss of optical purity after asymmetric conjugate addition.

Chromatography, High Pressure Liquid↗

Blood pressure and urinary cations in a low-fat intake Chinese population sample.

BACKGROUND: The relationship between cation intake and blood pressure (BP) in populations with specific dietary habits such as a low fat intake, remains unclear. A low fat intake has been prevalent during human evolution. METHODS: The average of 6 BP readings and heart rate (HR) recordings has been calculated. Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was collected. RESULTS: A highly significant correlation was found between the sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for Na/Cr and a negative one for K/Cr. The partial regression coefficient was in absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates highly significantly and independently with both SBP and DBP. CONCLUSION: If a Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.

Adolescent↗

Analysis of the coding and promoter regions of the autoantigen IA-2 in subjects with and without autoantibodies to IA-2.

Despite extensive studies on HLA polymorphism, there have been few, if any, studies on allelic forms or mutations in proteins that serve as autoantigens. The present experiments were designed to look for alterations in the coding and promoter regions of the autoantigen IA-2 in type one (insulin-dependent) diabetic patients with autoantibodies to IA-2 as compared with siblings without diabetes or autoantibodies to IA-2. Genomic DNA was used as a template and was amplified by polymerase chain reaction, with pairs of primers encompassing the promoter region and the 23 exons of the coding region of IA-2. A total of nine nucleotide changes were found in the coding region of the six type 1 diabetic patients; four were silent and five were missense changes, but all occurred in the extracellular domain of IA-2 to which autoantibodies are not directed. Few, if any, changes were found in the 5' upstream (-706 to +135) promoter region. The results of the experiments support the null hypothesis that differences among individuals in the nucleotide and amino acid sequences of the promoter and coding regions of IA-2, respectively, do not account for why some individuals develop autoantibodies to IA-2 and others do not.

Amino Acid Sequence↗

[Studies on the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang].

This paper first reported the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang. With the active constituents and yield of extracts as index, the each other effect of each drug and effect on total complex prescription in extraction were studied. And the effects of pressure and temperature were also studied. The results showed the effects were different in complex prescription extraction and single prescription. Active constituents can be extracted, but a obvious effect exist each other and effects together the yield of extract, extraction rate and content of active constituents of complex prescription extraction, which are concerned in extraction conditions. These study results have important reference on the modernization of traditional Chinese medicines.

Carbon Dioxide↗

[Diagnostic value of five serum markers for liver fibrosis].

OBJECTIVE: To research the diagnostic value of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), and transforming growth factor-beta(1) (TGF-beta(1)) for liver fibrosis in patients with chronic hepatitis. METHODS: Serum levels of HA, PCIII, CIV, LN and TGF-beta(1) in 116 patients with chronic hepatitis and cirrhosis were investigated and compared with hepatic histological findings of 87 patients. RESULTS: The correlation between serum HA and histologically assessed grade of inflammatory activity was weak (r=0.393, P<0.05). The correlation between serum HA, PCIII, LN, TGF-beta(1) and histologically assessed stage of liver fibrosis were all moderate (r=0.584, 0.454, 0.441 and 0.612, respectively, P<0.05), while that between serum CIV and histologically assessed stage of liver fibrosis was weak (r=0.319, P<0.05). As shown by the ROC curves in cases of chronic hepatitis, the ability to differentiate patients with cirrhosis from those without cirrhosis was greater for serum HA than that for serum PCIII, CIV, LN, and TGF-beta(1) (the areas under the curves=0.904 vs 0.784, 0.815, 0.805, 0.828, P<0.05). The ability of serum HA, LN and TGF-beta(1) to differentiate patients with extensive liver fibrosis from those with no or mild liver fibrosis exceeded that of serum PCIII and CIV (the areas under the curves=0.849, 0.819, 0.836 vs 0.702, 0.721, P<0.05). To discriminate the stage of liver fibrosis, serum HA and TGF-beta(1) were selected from the five markers by Bayes discriminate analysis. If S(1), S(2) and S(3) were not required to be discriminated, discrimination between the three stages showed significant difference (P<0.05). The predictive accurate percentage was 72.90%. CONCLUSIONS: The five markers all have the ability not only to judge liver cirrhosis, in which the ability of serum HA is the best, but also to differentiate chronic hepatitis with extensive liver fibrosis from that with no or mild liver fibrosis, in which the ability of serum HA, LN, TGF-beta(1) is stronger than the other two. It is useful for detection of serum HA and TGF-beta(1) at the same time to discriminate the histologically assessed stage of fibrosis. Serum HA and TGF-beta(1) can be helpful in discriminating patients of chronic hepatitis with "no liver fibrosis", "liver fibrosis but no cirrhosis" and "liver cirrhosis", but cannot discriminate them accurately as the histologically assessed stage of fibrosis. They cannot displace liver biopsy for the judgement of liver fibrosis.

Adult↗