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L Xu

Publications and source records attributed to L Xu.

At least 343 records · Page 19Linked to original sources
PubMed1999

Neuropharmacological assessment of potential dopamine D4 receptor-selective radioligands.

Radiolabeled dopamine D4 receptor-selective agents ([3H]1-benzyl-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [3 H]PNU-101958. and [125I]1-[4-iodobenzyl]-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine; [125I]RBI-257) were prepared and characterized. With D4.2- and D2L receptor-transfected cell membranes, [3H]PNU-101958 showed high dopamine D4 receptor affinity and selectivity, and potent inhibition by dopamine D4 receptor-selective compounds. However, its binding with rat brain homogenates showed little regional selectivity, and pharmacology inconsistent with selective dopamine D4 receptor labeling. Autoradiography indicated partial displacement of [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional selectivity, and lack of selective labeling with [125I]RBI-257. The results encourage further efforts to develop better dopamine D4 receptor-selective radioligands.

Aminopyridines↗
PubMed1999

Generation of retroviral vector for clinical studies using transient transfection.

Transient transfection of 293T cells was utilized to produce high-titer murine recombinant retroviral vectors for clinical studies. This system was initially optimized by gene transfer using different retroviral envelope proteins into activated human CD4+ T lymphocytes in vitro. Higher titer and infectivity were obtained than with stable murine producer lines; titers of 0.3-1 x 10(7) infectious units per milliliter for vectors encoding the green fluorescent protein (GFP) were achieved. Virions pseudotyped with envelope proteins from gibbon ape leukemia virus or amphotropic murine leukemia virus resulted in gene transfer of > or = 50% in CD4+ human T lymphocytes with this marker. Gene transfer of Rev M10 with this vector conferred resistance to HIV infection compared with negative controls in the absence of drug selection. Thus, the efficiency of transduction achieved under these conditions obviated the need to include selection to detect biologic effects in T cells. Finally, a protocol for the production of large-scale supernatants using transient transfection was optimized up to titers of 1.9 x 10(7) IU/ml. These packaging cells can be used to generate high-titer virus in sufficient quantities for clinical studies and will facilitate the rapid, cost-effective generation of improved retroviral, lentiviral, or other viral vectors for human gene therapy.

Animals↗
PubMed1999

CD45 modulation of CXCR1 and CXCR2 in human polymorphonuclear leukocytes.

All leukocytes express the cell surface glycoprotein CD45, which has intrinsic intracellular protein tyrosine phosphatase activity. CD45 is known to play a regulatory role in activation-induced signaling in lymphocytes; however, little is known of its role in non-lymphoid leukocytes. Therefore, we examined the potential effect of CD45 on chemokine-induced signaling in human neutrophils (polymorphonuclear cells, PMN). Treating isolated PMN for 2 h with an anti-CD45RB antibody (Bra11) down-modulated expression of the chemokine receptors CXCR1 and CXCR2 to 44 +/- 10% and 47 +/- 9% of their respective controls. The tyrosine kinase inhibitors genistein and herbimycin A significantly inhibited the Bra11-induced down-modulation of CXCR1 and CXCR2. Furthermore, Bra11-treated PMN were functionally inhibited in their capacity to exhibit IL-8-induced transient intracellular Ca2+ increases. Selected targeting of CXC receptors is indicated by the fact that N-formyl-Met-Leu-Phe (fMLP) receptor expression and function were not lost following Bra11 treatment. The effect of Bra11 on IL-8-mediated function and receptor expression was paralleled by decreased tyrosine phosphorylation of a 54- to 60-kDa protein. These findings indicate that CD45 can act to modulate PMN responses to chemokines; thus agents regulating CD45 can potentially modulate leukocyte traffic and may represent a novel therapeutic approach towards the treatment of inflammatory diseases.

Antibodies, Monoclonal↗
PubMed1999

Association of diabetes mellitus and chronic hepatitis C virus infection.

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.

Adult↗
PubMed1999

Empty and peptide-loaded class II major histocompatibility complex proteins produced by expression in Escherichia coli and folding in vitro.

The human class II major histocompatibility complex protein HLA-DR1 has been expressed in Escherichia coli as denatured alpha and beta subunits and folded in vitro to form the native structure. DR1 folding yields are 30-50% in the presence or absence of tight-binding antigenic peptides. The protein produced in this manner is soluble and monomeric with the expected apparent molecular weight. It reacts with conformation-sensitive anti-DR antibodies and exhibits peptide-dependent resistance to SDS-induced chain dissociation and to proteolysis as does the native protein. The observed peptide specificity and dissociation kinetics are similar to those of native DR produced in B-cells and finally the protein exhibits circular dichroism spectra and cooperative thermal denaturation as expected for a folded protein. We conclude that the recombinant DR1 has adopted the native fold. We have folded DR1 in the absence of peptide and isolated a soluble, peptide-free alphabeta-heterodimer. The empty DR1 can bind antigenic peptide but exhibits altered far UV-circular dichroism and thermal denaturation relative to the peptide-bound form.

Amino Acid Sequence↗
PubMed1999

Study on binding of REEs with water-soluble polysaccharides in fern.

The binding of rare earth elements (REEs) with water-soluble polysaccharides of nondeproteinization and deproteinization in the leaves of the fern Dicranopteris dichotoma was studied by molecular activation analysis (MAA). Two cold-water-soluble polysaccharides (extracted by 75% ethanol and 90% ethanol, respectively) and one hot-water-soluble polysaccharide (extracted by 90% ethanol) were separated using biochemical separation techniques. The eight rare earth elements (La, Ce, Nd, Sm, Eu, Tb, Yb, and Lu) in these polysaccharides were determined by instrumental neutron activation analysis. Our new results showed that the REEs were bound firmly with the water-soluble polysaccharides in the plant, regardless of whether nondeproteinization or deproteinization was used. The molecular-weight (MW) measurement demonstrated that REEs were mainly bound with low-MW (10,000-20,000) polysaccharides.

Chromatography, Ion Exchange↗
PubMed1999

Endovascular irradiation prevents smooth muscle cell proliferation and neointimal hyperplasia in rabbits.

The present study examined the temporal responses and the efficacy of 192Ir-HDR endovascular irradiation for preventing smooth muscle cell proliferation of rabbit iliac arteries after PTA with a cutting balloon catheter. Endovascular irradiation with 12 Gy was randomly performed on the one side of iliac arterial segment with the unirradiated side serving as a control. Animals were euthanatized 1, 2, 3, 4, 8 and 12 week(s) after angioplasty. Histopathological and immunohistochemical studies were carried out. Histopathology showed repair of the dissection by cellular accumulation and a striking reduction in the amount of neointimal hyperplasia in the irradiated arteries as compared with control vessels. A peak of PCNA-positive ratio was in neointima of the control arterial segments at a week. 2-4 weeks after irradiation, the neointimal PCNA-positive ratio was still significantly increased in the control arterial segments compared with the irradiated arterial segments. After 8 weeks, PCNA-positive ratio was below 1% in both irradiated arterial segments and the control. Our results showed that the 192Ir-HDR afterloading irradiation with a dose of 12 Gy can be considered sufficient for inhibiting neointimal hyperplasia in angioplastized rabbit iliac arteries with cutting balloon catheter.

Angioplasty, Balloon, Coronary↗
PubMed1999

Normal changes in spinal bone mineral density in a Chinese population: assessment by quantitative computed tomography and dual-energy X-ray absorptiometry.

This study was designed to determine age- and gender-based normative values for spinal bone mineral density (BMD) in a Chinese population. In addition, we compared our data with those of other countries and populations. Four hundred and forty-three healthy Chinese subjects, aged 10-79 years (189 males, mean age 46.9 years; 254 females, mean age 45.7 years) were recruited for BMD assessment. BMD was measured by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA), including posteroanterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). For both genders, BMD values peaked in the 10-19 year age group when measured by QCT, and in the 30-39 year age group when measured by PA-DXA. BMD values decreased with age after reaching peak bone density in males and females for all measurements, except for PA-DXA in males. Male BMD values by DXA tended to increase beginning with the 60-69 age group through the 70-79 age group whether by PA-DXA, or L-DXA and mL-DXA. However, male QCT data showed stable BMD values among these two older groups. Comparative results showed female QCT data were higher in the 20-39 age group and lower after the 40-49 age group compared with American females. The peak BMD value by PA-DXA in Chinese females was reached in the same age group as American and European females and was similar in magnitude (p > 0.05). However, the peak BMD value for Chinese females was reached earlier and was significantly higher than that observed in Japanese females (p < 0.001). We conclude that the age group in which the peak BMD values are reached is different depending on the technique used, as is the calculated age-related rate of bone loss. It can be speculated that such differences reflect different timing for bone maturation in cancellous and cortical bone.

Absorptiometry, Photon↗
PubMed1999

International variation in the incidence of hip fractures: cross-national project on osteoporosis for the World Health Organization Program for Research on Aging.

A cross-national study of hip fracture incidence was carried out in five geographic areas--Beijing, China; Budapest, Hungary; Hong Kong; Porto Alegre, Brazil; and Reykjavik, Iceland--during the years 1990-1992. Cases of hip fracture among women and men of age 20 years and older were identified using hospital discharge data in conjunction with medical records, operating room logs, and radiology logs. Estimated incidence rates varied widely, with Beijing reporting the lowest rates (age-adjusted rate per 100,000 population for men 20 years and older = 45.4; women = 39.6) and Reykjavik the highest rates (man = 141.3; women = 274.1). Rates were higher for women than for men in every area except Beijing. In every area except Budapest, review of the operating room or radiology logs identified additional cases that were not reported in the discharge list, increasing the estimated number of hip fractures by 11% to 62%, depending on the area. Review of medical records identified miscoding of hip fractures (ICD 9820) as 'shaft of femur and other femur fractures' (ICD 9821) in the discharge lists of every area except Budapest, increasing the estimated number of hip fractures by 1% to 30%. The final estimates of hip fracture incidence taking into account all investigated sources of undercount and overcount ranged from 15% lower to 89% higher than an estimate based on the discharge diagnoses alone. Although these results indicate substantial limitations in relying on hospital discharge data alone to estimate hip fracture incidence rates, the extent of errors found in the discharge lists is smaller than the large international variation found here and previously reported in incidence rates. The findings support the conclusion that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates.

Adult↗
PubMed1999

Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase deficiency (HCS) is an autosomal recessive disorder characterized by metabolic ketoacidosis, abnormal urine organic metabolites, and dermatitis. These symptoms are improved by pharmacological doses of biotin. In this study, we have analyzed seven patients with HCS deficiency found in European and Middle Eastern countries by using reverse transcription/polymerase chain reaction/single-stranded conformation polymorphism and a sequencing analysis. Although we had previously reported that two mutations were frequent in Japanese patients, no frequent mutations were found in the patients analyzed in this study. Seven novel mutations were identified in the cDNA of the patients; these included three missense mutations, two single-base deletions that resulted in a termination codon, a three-base in-frame deletion, and a 68-bp deletion. A new polymorphism C1121T was also identified in four alleles. A transient expression study demonstrated that the HCS activities of three missense mutations and one amino acid deletion were 1%-14% that of wild-type cDNA; in contrast, the activities of the two single-base deletions followed by a termination codon and Asp571Asn were nearly undetectable. These data suggest that a variety of mutations is responsible for decreasing HCS activity and that the aspartate residue at amino acid position 571 may be crucial for the catalytic activity of HCS.

Carbon-Nitrogen Ligases↗
PubMed1999

Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome.

Endothelial injury is the primary pathogenic event leading to the renal thrombotic microangiopathic lesions typical of the hemolytic uremic syndrome (HUS). Basic fibroblast growth factor (bFGF) is an angiogenic growth factor released by injured endothelial cells. In a previous study we have found a significant accumulation of bFGF in human immunodeficiency virus (HIV)-transgenic mice with renal disease. Here we investigated whether bFGF was accumulated in the circulation and kidneys of two children with HIV-associated HUS (HIV-HUS), and studied the mechanisms involved in this process. The plasma levels of bFGF in children with HIV-HUS (124+/-20 pg/ml) were increased compared with five children with HIV nephropathy (49+/-6 pg/ml) and twenty HIV-infected children without renal disease (26+/-4 pg/ml, P<0.001). Immunohistochemistry and receptor binding studies showed that bFGF was accumulated bound to heparan sulfate proteoglycans in renal glomeruli and interstitium surrounding renal tubules in HIV-HUS kidneys. Basic FGF stimulated the proliferation of mesangial and urinary renal tubular epithelial cells isolated from both patients. These findings support the hypothesis that bFGF and its low-affinity binding sites may play a relevant role in modulating the process of glomerular and renal tubular regeneration during the acute stages of HIV-HUS. A follow-up study in a larger sample population is required to confirm these results.

AIDS-Associated Nephropathy↗
PubMed1999

Selectivity and permeation in calcium release channel of cardiac muscle: alkali metal ions.

Current was measured from single open channels of the calcium release channel (CRC) of cardiac sarcoplasmic reticulum (over the range +/-180 mV) in pure and mixed solutions (e.g., biionic conditions) of the alkali metal ions Li+, K+, Na+, Rb+, Cs+, ranging in concentration from 25 mM to 2 M. The current-voltage (I-V) relations were analyzed by an extension of the Poisson-Nernst-Planck (PNP) formulation of electrodiffusion, which includes local chemical interaction described by an offset in chemical potential, which likely reflects the difference in dehydration/solvation/rehydration energies in the entry/exit steps of permeation. The theory fits all of the data with few adjustable parameters: the diffusion coefficient of each ion species, the average effective charge distribution on the wall of the pore, and an offset in chemical potential for lithium and sodium ions. In particular, the theory explains the discrepancy between "selectivities" defined by conductance sequence and "selectivities" determined by the permeability ratios (i.e., reversal potentials) in biionic conditions. The extended PNP formulation seems to offer a successful combined treatment of selectivity and permeation. Conductance selectivity in this channel arises mostly from friction: different species of ions have different diffusion coefficients in the channel. Permeability selectivity of an ion is determined by its electrochemical potential gradient and local chemical interaction with the channel. Neither selectivity (in CRC) seems to involve different electrostatic interaction of different ions with the channel protein, even though the ions have widely varying diameters.

Animals↗
PubMed1999

IL-2 enhances allergic airway responses in rats by increased inflammation but not through increased synthesis of cysteinyl leukotrienes.

BACKGROUND: IL-2 has been shown to increase allergic airway responses in rats. OBJECTIVE: The purpose of this study was to investigate whether induction of inflammation and enhancement of cysteinyl-leukotriene (cys-LT) synthesis were involved in the augmentation of airway responses caused by IL-2. METHODS: Brown Norway rats received human recombinant IL-2 or saline subcutaneously twice a day from day 9 to day 14 after sensitization to ovalbumin (OVA). On day 14, rats underwent either lung lavage or were challenged with an aerosol spray of OVA, the airway responses and biliary excretion of cys-LTs were measured for a period of 8 hours after challenge, and the lung leukocyte numbers were determined after enzymatic digestion of lung tissues. RESULTS: The early response after OVA increased from 184.2% +/- 13.5% in the animals receiving saline (n = 10) to 309% +/- 51% (baseline lung resistance) in IL-2-pretreated animals (n = 17; P <.05). The late response also increased from 19.6 +/- 4.5 (area under the curve of baseline lung resistance vs time) in the animals receiving saline to 37 +/- 5.4 after administration of IL-2 (P <.05). However, IL-2-treated animals had lower levels of biliary cys-LTs during the late response than saline-treated animals but similar levels during the early response. This difference could not be attributed to an increase in LT metabolism, which we assessed by the recovery of 3H-LTC4 instilled intratracheally in challenged or unchallenged rats. When compared with control animals, pretreatment with IL-2 increased all cell types retrieved from lung lavage fluid before OVA challenge (P <.05). After OVA challenge, the total cell yield from lung lavage fluid was also increased, mostly because of an increase in neutrophils (P <.05). Eosinophils and lymphocytes were greater in the lungs of IL-2-treated than vehicle-treated and OVA-challenged rats (P <.01), and IL-2-treated rats had a lower CD4(+)/CD8(+) ratio in the blood after challenge (P <.001). CONCLUSION: In conclusion, IL-2 increases early and late responses in rats, and it induces lung inflammation. Altered airway responses are not attributable to an increase in cys-LT production.

Animals↗
PubMed1999

Improved learning algorithms for mixture of experts in multiclass classification.

Mixture of experts (ME) is a modular neural network architecture for supervised learning. A double-loop Expectation-Maximization (EM) algorithm has been introduced to the ME architecture for adjusting the parameters and the iteratively reweighted least squares (IRLS) algorithm is used to perform maximization in the inner loop [Jordan, M.I., Jacobs, R.A. (1994). Hierarchical mixture of experts and the EM algorithm, Neural Computation, 6(2), 181-214]. However, it is reported in literature that the IRLS algorithm is of instability and the ME architecture trained by the EM algorithm, where IRLS algorithm is used in the inner loop, often produces the poor performance in multiclass classification. In this paper, the reason of this instability is explored. We find out that due to an implicitly imposed incorrect assumption on parameter independence in multiclass classification, an incomplete Hessian matrix is used in that IRLS algorithm. Based on this finding, we apply the Newton-Raphson method to the inner loop of the EM algorithm in the case of multiclass classification, where the exact Hessian matrix is adopted. To tackle the expensive computation of the Hessian matrix and its inverse, we propose an approximation to the Newton-Raphson algorithm based on a so-called generalized Bernoulli density. The Newton-Raphson algorithm and its approximation have been applied to synthetic data, benchmark, and real-world multiclass classification tasks. For comparison, the IRLS algorithm and a quasi-Newton algorithm called BFGS have also been applied to the same tasks. Simulation results have shown that the use of the proposed learning algorithms avoids the instability problem and makes the ME architecture produce good performance in multiclass classification. In particular, our approximation algorithm leads to fast learning. In addition, the limitation of our approximation algorithm is also empirically investigated in this paper.

Journal Article↗
PubMed1999

Coactivator and corepressor complexes in nuclear receptor function.

The nuclear hormone receptors constitute a large family of transcription factors. The binding of the hormonal ligands induces nuclear receptors to assume a configuration that leads to transcriptional activation. Recent studies of retinoic acid and thyroid hormone receptors revealed that, upon ligand binding, a histone deacetylase (HDAC)-containing complex is displaced from the nuclear receptor in exchange for a histone acetyltransferase (HAT)-containing complex. These observations suggest that ligand-dependent recruitment of chromatin-remodeling activity serves as a general mechanism underlying the switch of nuclear receptors from being transcriptionally repressive to being transcriptionally active.

Animals↗
PubMed1999

Ultrasonically guided inferior vena cava stent placement: experience in 83 cases.

PURPOSE: Traditionally, inferior vena cava (IVC) stent placement is performed with fluoroscopic guidance. The object of this study was to evaluate use of ultrasound (US) as guidance for IVC stent placement for the management of Budd-Chiari syndrome. MATERIALS AND METHODS: Eighty-three patients with IVC membranous stenosis (n = 30), membranous occlusion (n = 19), segmental stenosis (n = 21), or segmental occlusion (n = 13) underwent IVC recanalization, balloon dilation, and stent placement under US guidance. Among the 83 patients, 67 had at least one patent hepatic vein, while 16 patients had three occluded hepatic veins. RESULTS: IVC stents were successfully placed in 79 of 83 patients, with a success rate of 95%. After the procedure, the symptoms and signs of IVC obstruction disappeared or markedly improved in all patients, and the blockage of hepatic outflow was alleviated in 67 patients. Pericardial effusion, complete atrial ventricular block, and stent migration into the right atrium occurred, respectively, in one patient. During 1-46-month follow-up, stent restenosis occurred in one patient; the other stents remained open and functioned effectively. CONCLUSION: Because of the absence of nonionizing radiation and iodinated contrast material, and its low cost, US is well suited and often preferred for guidance of IVC stent placement.

Adolescent↗
PubMed1999

Notch1 expression in early lymphopoiesis influences B versus T lineage determination.

Notch receptors regulate fate decisions in many cells. One outcome of Notch signaling is differentiation of bipotential precursors into one cell type versus another. To investigate consequences of Notch1 expression in hematolymphoid progenitors, mice were reconstituted with bone marrow (BM) transduced with retroviruses encoding a constitutively active form of Notch1. Although neither granulocyte or monocyte differentiation were appreciably affected, lymphopoiesis was dramatically altered. As early as 3 weeks following transplantation, mice receiving activated Notch1-transduced BM contained immature CD4+ CD8+ T cells in the BM and exhibited a simultaneous block in early B cell lymphopoiesis. These results suggest that Notch1 provides a key regulatory signal in determining T lymphoid versus B lymphoid lineage decisions, possibly by influencing lineage commitment from a common lymphoid progenitor cell.

Animals↗