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L Xu

Publications and source records attributed to L Xu.

At least 109 records · Page 6Linked to original sources
PubMed2001

Classes of thiols that influence the activity of the skeletal muscle calcium release channel.

The skeletal muscle Ca(2+) release channel/ryanodine receptor (RyR1) is a prototypic redox-responsive ion channel. Nearly half of the 101 cysteines per RyR1 subunit are kept in a reduced (free thiol) state under conditions comparable with resting muscle. Here we assessed the effects of physiological determinants of cellular redox state (oxygen tension, reduced (GSH) or oxidized (GSSG) glutathione, and NO/O(2) (released by 3-morpholinosydnonimine)) on RyR1 redox state and activity. Oxidation of approximately 10 RyR1 thiols (from approximately 48 to approximately 38 thiols/RyR1 subunit) had little effect on channel activity. Channel activity increased reversibly as the number of thiols was further reduced to approximately 23/subunit, whereas more extensive oxidation (to approximately 13 thiols/subunit) inactivated the channel irreversibly. Neither S-nitrosylation nor tyrosine nitration contributed to these effects. The results identify at least three functional classes of RyR1 thiols and suggest that 1) the channel may be protected from oxidation by a large reservoir of functionally inert thiols, 2) the channel may be designed to respond to moderate oxidative stress by a change in activation setpoint, and 3) the channel is susceptible to oxidative injury under more extensive conditions.

Animals↗
PubMed2001

Identification and expression of the motilin precursor in the guinea pig.

Motilin has never been isolated from rodents, the most frequently used laboratory animals, despite several attempts. We have isolated and sequenced the motilin precursor from duodenal mucosa of guinea pig (GenBank accession number AF323752) and studied its expression in several tissues. The percent homology with human motilin is the lowest yet observed due to several unique substitutions in the C-terminal end. As expected, the precursor was present in the gut mucosa with the exception of the gastric corpus. It was also present in medulla oblongata, nucleus of the solitary tract, hypophysis, spinal cord, hypothalamus, and cerebellum but not in the cerebral cortex. For the first time we demonstrated motilin expression in the thyroid.

Amino Acid Sequence↗
PubMed2001

Palladium-catalyzed regioselective arylation of an electron-rich olefin by aryl halides in ionic liquids.

[figure: see text] Palladium-catalyzed arylation of the electron-rich olefin butyl vinyl ether has been accomplished in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]), using as the arylating agents aryl iodides and bromides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeds with high efficiency and remarkable regioselectivity, leading almost exclusively to substitution by various aryl groups at the olefinic carbon alpha to the heteroatom of butyl vinyl ether.

Journal Article↗
PubMed2001

Microsatellite instability at AAAG repeat sequences in respiratory tract cancers.

We surveyed the occurrence of novel alleles at microsatellite sequences in non-small cell lung cancers (NSCLC) using 61 tetranucleotide repeat markers. The presence of at least one new allele, consistent with microsatellite instability (MSI), was observed in 26 of 61 (43%) markers involving 30 of 47 (64%) NSCLC. Twelve of the 26 markers detected new alleles in 2 or more tumors and 11 of these 12 markers contained an AAAG repeat sequence. Using this panel of 12 markers, MSI was detected in 24 of 47 (51%) NSCLC and 10 of 18 (56%) head and neck cancers but was only observed in 8 of 38 (21%) bladder cancers and 3 of 25 (12%) kidney cancers. Our results suggested that about 50% of respiratory tract cancers exhibited microsatellite instability predominantly at AAAG sequences. This distinct type of instability was termed EMAST for elevated microsatellite alterations at selected tetranucleotide repeats. The identification of markers with EMAST should have potential application for the molecular detection of respiratory tract cancers.

Aged↗
PubMed2001

Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study.

OBJECTIVE: To estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) in a population-based sample of elderly subjects in Beijing, China and compare it with that reported in the Framingham (Massachusetts) OA Study. METHODS: We recruited a sample of persons age > or = 60, using door-to-door enumeration in randomly selected neighborhoods in Beijing. Subjects completed a home interview including questions on knee symptoms and a hospital examination including knee radiographs obtained during weight bearing. The protocol was identical to that used in the Framingham OA Study. A reader read intermingled Beijing and Framingham Study films to ensure high reliability. We defined a subject as having radiographic knee OA when the Kellgren/Lawrence grade was > or = 2 in at least 1 knee. Symptomatic knee OA was recorded as present when knee pain was reported and the symptomatic knee had radiographic OA. We estimated the prevalence of these entities in elderly subjects in Beijing and compared it with OA prevalence in Framingham, using an age-standardized prevalence ratio. RESULTS: Of 2,180 age-eligible Beijing subjects contacted, knee radiographs were obtained in 1,787 (82.0%). The prevalence of radiographic knee OA was 42.8% in women and 21.5% in men. Symptomatic knee OA occurred in 15.0% of women and 5.6% of men. Compared with women of the same age in Framingham, women in Beijing had a higher prevalence of radiographic knee OA (prevalence ratio 1.45, 95% confidence interval 1.31-1.60) and of symptomatic knee OA (prevalence ratio 1.43, 95% confidence interval 1.16-1.75). The prevalence of knee OA in Chinese men was similar to that in their white US counterparts (for radiographic OA, prevalence ratio 0.90; for symptomatic OA, prevalence ratio 1.02). CONCLUSION: Using identical methods and definitions to evaluate the prevalence of OA across populations, we found, surprisingly, that older Chinese women have a higher prevalence of knee OA than women in Framingham, Massachusetts. The prevalence in men was comparable. Possible explanations for these differences range from genetic differences to heavy physical activity among Chinese.

Age Distribution↗
PubMed2001

Differential neuroprotection from human heat shock protein 70 overexpression in in vitro and in vivo models of ischemia and ischemia-like conditions.

We previously showed that overexpressing the 70-kDa inducible heat shock protein in primary astrocyte cultures and in a rodent stroke model using viral vectors resulted in protection from ischemia and ischemia-like injury. However, viral transfection could potentially provoke a stress response itself; therefore, we examined whether transgenic mice constitutively expressing human heat shock protein 70 were protected from ischemic insults. Astrocyte cultures from brains of heat shock protein 70 transgenic mice were resistant to hydrogen peroxide injury in a dose-dependent fashion, but were less resistant to hypoglycemia and oxygen-glucose deprivation. Because hydrogen peroxide exposure and glucose deprivation are partially dependent on glutathione levels, we determined whether heat shock protein 70 transgenic cultures had altered glutathione levels under normal growth conditions. However, there was no significant difference in glutathione levels between heat shock protein 70 transgenic and wildtype astrocytes. Hippocampal, but not cortical neuron cultures from these same transgenic mice were also protected against oxygen-glucose deprivation and glutamate toxicity. In an in vivo model of permanent focal cerebral ischemia, there was no significant difference in infarct size assessed 24 h postinsult. These results suggest that heat shock protein 70 protects against some but not all kinds of central nervous system injury. The protective effects may be related to the nature and severity of the insults, as well as subpopulations of brain cells and dose-dependent effects of HSP70 overexpression.

Animals↗
PubMed2001

Differential sensitivity of murine astrocytes and neurons from different brain regions to injury.

Different brain regions show differential vulnerability to ischemia in vivo. Despite this, little work has been done to compare vulnerability of brain cells isolated from different brain regions to injury. Relatively pure neuronal and astrocyte cultures were isolated from mouse cortex, hippocampus, and striatum. Astrocyte vulnerability to 6 h oxygen-glucose deprivation was greatest in striatum (81.8 +/- 4.6% cell death), intermediate in hippocampus (59.8 +/- 4.8%), and least in cortex (37.0 +/- 3.5%). In contrast neurons deprived of oxygen and glucose for 3 h showed greater injury to cortical neurons (71.1 +/- 5.2%) compared to striatal (39.0 +/- 3.1%) or hippocampal (39.0 +/- 5.3%) neurons. Astrocyte injury from glucose deprivation or H(2)O(2) exposure was significantly greater in cells from cortex than from striatum or hippocampus. Neuronal injury resulting from serum deprivation was greater in cortical neurons than in those from striatum or hippocampus, while excitotoxic neuronal injury was equivalent between regions. Antioxidant status and apoptosis-regulatory genes were measured to assess possible underlying differences. Glutathione was higher in astrocytes and neurons isolated from striatum than in those from hippocampus. Superoxide dismutase activity was significantly higher in striatal astrocytes, while glutathione peroxidase activity and superoxide did not differ by brain region. Bcl-x(L) was significantly higher in striatal astrocytes than in astrocytes from other brain regions and higher in striatal and hippocampal neurons than in cortical neurons. Both neurons and astrocytes isolated from different brain regions demonstrate distinct patterns of vulnerability when placed in primary culture. Antioxidant state and levels of expression of bcl-x(L) can in part account for the differential injury observed. This suggests that different protective strategies may have different efficacies depending on brain region.

Animals↗
PubMed2001

A spontaneous canine model of mucous membrane (cicatricial) pemphigoid, an autoimmune blistering disease affecting mucosae and mucocutaneous junctions.

Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering dermatosis of humans that was previously known as cicatricial pemphigoid. It is characterized by vesicles, ulcers and scarring that affect predominantly mucosae and mucocutaneous junctions. Circulating autoantibodies recognize epitopes on basement membrane proteins such as collagen XVII or laminin-5/6. Herein, we describe the clinico-pathological and immunological characteristics of 17 dogs afflicted with a dermatosis homologous to MMP of humans. Patients exhibited vesicles and erosions predominantly on mucous membranes or mucocutaneous junctions of the mouth, nose, eyes, genitalia or anus. Histopathology revealed subepithelial vesicles with variable dermal inflammation. Direct immunofluorescence demonstrated IgG or complement at the dermoepithelial junction. Indirect immunofluorescence using salt-split epithelia permitted the detection of circulating basement membrane-specific IgG autoantibodies in 15 cases. In 11 patients, autoantibodies recognized the NC16A segment of collagen XVII, as determined by salt-split indirect immunofluorescence, immunoblotting using canine keratinocytes and ELISA with synthetic canine peptides. In one dog, autoantiodies bound to the dermal side of salt-split epithelia and recognized epitopes within the 30 kDa carboxy-terminal segment of human collagen XVII. Canine MMP, like its human counterpart, exhibits distinctive clinical signs and histopathological lesions, yet circulating autoantibodies target different antigenic epitopes. This spontaneous canine model of MMP could prove useful for studies on the pathogenesis or therapy of this human disease.

Animals↗
PubMed2001

A versatile framework for the design of ligand-dependent, transgene-specific transcription factors.

The ability to regulate transgene expression will be essential for the safety and efficacy of many gene therapies. Various ligand-dependent transcription factors, including steroid hormone receptors, have been modified to enable transgene-specific regulation. To minimize effects on cellular gene expression, chimeric steroid receptors have been constructed by replacing their native DNA binding domain (DBD) with a heterologous DBD, like that from the yeast transcription factor GAL4. This approach has limitations for human gene therapy, including the potential immunogenicity of the GAL4 domain and the inability to discriminate between different GAL4-linked transgenes in the same cell. To address this, we have constructed chimeric regulators containing the human estrogen receptor (ER) ligand binding domain (LBD) and a Cys(2)-His(2)-type zinc finger DBD. Cys(2)-His(2) zinc finger domains are common among human DNA binding proteins and can be engineered to selectively bind different DNA sequences. We demonstrate over 500-fold drug-dependent transgene induction with these chimeric regulators in vitro and the ability to regulate an adenovirus-delivered transgene in mice. Two chimeras containing different Cys(2)-His(2) domains displayed highly sequence-specific binding and regulation. Incorporating a point mutation in the ER LBD that ablates estrogen binding enables selective in vivo regulation with the clinically useful anti-estrogen tamoxifen. These Cys(2)-His(2)-ER LBD chimeras represent a versatile framework for creating transgene-specific regulators potentially useful for human gene therapy applications.

Adenoviridae↗
PubMed2001

Kat1-antigen--a reliable immunological marker for identifying osteoclast precursors of rats: detection of subpopulations among precursors and initiation of osteoclastogenesis.

Previously we found a unique cell surface antigen [Kat1-antigen (Kat1-Ag)] expressed on rat osteoclasts. In the present study, we focused on the expression of this antigen in preosteoclasts, mononuclear precursors of osteoclasts. Immunohistochemical and immunoelectron microscopic observations of the Kat1-Ag expressed in vivo showed the antigen to be present on mononuclear cells having the morphological features of preosteoclasts. The relationship between Kat1-Ag expression and calcitonin receptor (CTR) expression was examined in detail by a double-detection technique for CTR and Kat1-Ag by use of autoradiography and immunocytochemistry, respectively. In a culture system for forming mononuclear preosteoclast-like cells, almost 100% of the mononuclear cells expressing Kat1-Ag also expressed CTR, demonstrating that Kat1-Ag is a reliable immunological marker for identifying preosteoclasts. Interestingly, a significant number of the CTR-positive mononuclear cells did not express the Kat1-Ag. Detection of these cells expressing CTR but not Kat1-Ag strongly suggests the presence of subpopulations in preosteoclasts. We also obtained evidence suggesting that expression of the Kat1-Ag is initiated during the postmitotic stage of the osteoclast progenitors.

Animals↗
PubMed2001

Effects of electrode configuration and place of stimulation on speech perception with cochlear prostheses.

Recent research and clinical experience with cochlear implants suggest that subjects' speech recognition with monopolar or broad bipolar stimulation might be equal to or better than that obtained with narrow bipolar stimulation or other spatially restricted electrode configurations. Furthermore, subjects often prefer the monopolar configurations. The mechanisms underlying these effects are not clear. Two hypotheses are (a) that broader configurations excite more neurons resulting in a more detailed and robust neural representation of the signal and (b) that broader configurations achieve a better spatial distribution of the excited neurons. In this study we compared the effects of electrode configuration and the effects of longitudinal placement and spacing of the active electrodes on speech recognition in human subjects. We used experimental processor maps consisting of 11 active electrodes in a 22-electrode scala tympani array. Narrow bipolar (BP), wide bipolar (BP + 6), and monopolar (MP2) configurations were tested with various locations of active electrodes. We tested basal, centered, and apical locations (with adjacent active electrodes) and spatially distributed locations (with every other electrode active) with electrode configuration held constant. Ten postlingually deafened adult human subjects with Nucleus prostheses were tested using the SPEAK processing strategy. The effects of electrode configuration and longitudinal place of stimulation on recognition of CNC phonemes and words in quiet and CUNY sentences in noise (+10 dB S/N) were similar. Both independent variables had large effects on speech recognition and there were interactions between these variables. These results suggest that the effects of electrode configuration on speech recognition might be due, in part, to differences among the various configurations in the spatial location of stimulation. Correlations of subjective judgments of sound quality with speech-recognition ability were moderate, suggesting that the mechanisms contributing to subjective quality and speech-recognition ability do not completely overlap.

Adult↗
PubMed2001

DNA adduct formation and DNA strand breaks in green-lipped mussels (Perna viridis) exposed to benzo[a]pyrene: dose- and time-dependent relationships.

Green-lipped mussels, Perna viridis, were exposed to 0, 0.3, 3 and 30 micrograms l-1 (nominal concentrations) B[a]P under laboratory conditions over a period of 24 days. Mussels were collected on day 0, 1, 3, 6, 12, 18 and 24, and the levels of DNA adducts and DNA strand breaks in their hepatopancreas tissues monitored. Mussels exposed to 0.3 and 3 micrograms l-1 B[a]P showed marked increases in strand breaks after 1 day of exposure. DNA strand break levels in these mussels remained high and significantly different from the control values until day 3 for the 0.3 microgram l-1 treatment group, and day 6 for the 3 micrograms l-1 treatment group. This was followed by a gradual reduction in strand breaks. After 12 days, the levels of both groups had returned to the same level as that of the control. No increase in DNA strand breaks was observable in mussels exposed to 30 micrograms l-1 B[a]P in the first 12 days of exposure, but a significant increase was observed from day 12 to day 24. Increasing B[a]P concentrations resulted in elevated DNA adduct levels after 3-6 days of exposure, but this pattern of dose-related increase disappeared after 12 days. These results indicate that a better understanding of the complex interactions between exposure levels and durations is crucially important before DNA adduct levels and DNA strand breaks in P. viridis can be used as effective biomarkers for monitoring genotoxicants in marine waters.

Animals↗
PubMed2001

Detection of prawn white spot bacilliform virus by immunoassay with recombinant antigen.

Prawn white spot bacilliform virus (WSBV) is the major pathogen of prawn disease. To develop a sensitive assay for the early detection of this virus, we generated an antibody against a WSBV-specific protein, P204. The p204 gene was cloned from a WSBV cDNA library and expressed in Escherichia coli. The peptide (P204) encoded by p204 was purified, and its antibody raised in mice. IgG fraction of the anti-P204 serum was purified using a Sepharose column and the Fab fragment was obtained by pepsin digestion. An enzyme-linked immunosorbent assay (ELISA) using this Fab fragment was developed to detect the WSBV in prawn tissues. The experiments showed that Fab of anti-P204 antibody is highly specific for WSBV, and displays a sensitivity of 10(5) viral particles/mg prawn tissues. This is the first report using the Fab fragment prepared from a recombinant antigen to detect prawn viruses by ELISA.

Animals↗
PubMed2001

Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio.

The traditional workup for primary aldosteronism is cumbersome and requires discontinuing antihypertensive medications, which is inconvenient and potentially dangerous. A simple and accurate screening test that can be used without modifying medications is needed. The plasma aldosterone-renin ratio (ARR) is a valid screening assay for primary aldosteronism, but antihypertensives are usually discontinued before obtaining this ratio, limiting its utility. The present prospective study is designed to examine the validity of the ARR as a screening test for primary aldosteronism if the ratio is measured randomly while patients continue antihypertensive therapy. During the 18-month study period, 90 patients were referred to the hypertension clinic with poorly controlled hypertension. ARR was measured in random blood samples in all 90 patients while maintaining their prescribed antihypertensive medications. Those with elevated ARRs (>100 ng/dL / ng/mL/h) underwent further diagnostic workup, including adrenal computed tomography and/or magnetic resonance imaging and adrenal iodine 131 norcholesterol uptake scan. Fifteen patients (17%) had elevated ARRs greater than 100:1. Ten of 15 patients were found to have adrenal adenoma on diagnostic workup, and adenoma was later confirmed by histological examination after surgical removal in these 10 patients. Five patients were found to have adrenal hyperplasia; all 5 patients responded to antialdosterone treatment. Thus, all 15 patients had good control of blood pressure after surgery and/or antialdosterone medications. No patient showed a falsely elevated ARR. Data suggest that the ARR is a valid screening assay for primary aldosteronism in patients with poorly controlled blood pressure, and discontinuation of antihypertensive medications is not needed for this test.

Adenoma↗
PubMed2001

The effect of monaural middle ear destruction on postnatal development of auditory response properties of mouse inferior collicular neurons.

This study examined the effect of monaural middle ear destruction on postnatal development of auditory response properties of inferior collicular (IC) neurons of the laboratory mouse, Mus musculus. Monaural middle ear destruction was performed on juvenile and adult mice and the auditory response properties of neurons in both ICs were examined 4 weeks thereafter. IC neurons of control mice typically had lower minimum thresholds, larger dynamic ranges and greater Q(10) values than IC neurons of experimental juvenile and adult mice. In experimental mice, neurons in the ipsilateral IC (relative to the intact ear) typically had longer latencies, higher minimum thresholds, and smaller dynamic ranges than neurons in the contralateral IC. In experimental adult mice, neurons in the ipsilateral IC had sharper frequency tuning curves than neurons in the contralateral IC. Clear tonotopic organization was only observed in the IC of control mice and experimental adult mice. However, the correlation of increasing minimum threshold with best frequency was observed for IC neurons in control mice but not in experimental juvenile and adult mice. Possible mechanisms for these different response properties are discussed.

Acoustic Stimulation↗
PubMed2001

Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial stunning in an ischemia-reperfusion model.

OBJECTIVES: Our objective was to determine the effect of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NNA) on free radical generation and myocardial contractility after ischemia-reperfusion. BACKGROUND: Cardiotoxic free radicals are generated by ischemia-reperfusion sequences. Nitric oxide reacts with superoxide radical to form peroxynitrite, which generates additional free radicals. Our hypothesis was that by inhibiting NO production, free radical formation will be diminished, which should be cardioprotective. METHODS: We studied 32 dogs. Coronary occlusion-reperfusion (20 min each) sequences were created by intracoronary balloon angioplasty inflation-deflation. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of total oxidative flux. The L-NNA (4.8 mg/kg total) was infused intravenously during occlusion-reperfusion; control dogs received saline. Immunohistochemical staining demonstrated the peroxynitration product nitrotyrosine. RESULTS: In the control dogs Asc*- rose from 3.2 +/- SD 0.5 nmol/l to 4.8 +/- 1.1 nmol/l with reperfusion, a 50% rise. With L-NNA the Asc*- rose from 3.2 +/- 0.9 nmol/l to 4.0 +/- 1.2 nmol/l, a 25% rise (p < 0.01, L-NNA vs. control). Echocardiographic left ventricular fractional area shortening (FAS) in the control dogs declined from 38 +/- 19% (baseline) to 26 +/- 14% (ischemia), and to 22 +/- 11% with reperfusion (p < 0.01 vs. baseline). With L-NNA, FAS declined from 36 +/- 13% (baseline) to 27 +/- 12% (ischemia) but then rose to 33 +/- 14 with reperfusion (p = NS vs. baseline). Nitrotyrosine was present in the myocardium subjected to ischemia-reperfusion, but almost absent in dogs receiving L-NNA. Myocardial perfusion was not altered by L-NNA. CONCLUSIONS: The NO synthase inhibitors decrease coronary sinus free radical concentration and ameliorate myocardial stunning after ischemia-reperfusion.

Animals↗