Biomedical subjects

Yan Xu

Publications and source records attributed to Yan Xu.

At least 181 records · Page 10Linked to original sources

PubMed2003

An LOH and mutational investigation of the ST7 gene locus in human esophageal carcinoma.

Frequent loss of heterozygosity (LOH) on human chromosome 7q31 has been reported in numerous malignancies. Suppressor of tumorigenicity 7 (ST7) has been identified as a candidate tumor suppressor gene in this region. To identify whether 7q31 and genetic alterations of ST7 were involved in human esophageal carcinogenesis, we performed LOH mapping of a 5.4 cM region at 7q31-q35 in 43 primary esophageal carcinomas, as well as mutational analyses of the ST7 gene in tumors with LOH in this region. Of 43 tumors, 12 (28%) showed LOH at 7q31-q35. These included four (22%) of 18 squamous cell carcinomas and eight (32%) of 25 adenocarcinomas. The peak LOH locus was D7S480, lying 4.2 Mb telomeric to ST7 and showing LOH in eight of 37 informative tumors, or 22%. No mutations were found in the entire coding or flanking intronic regions of the ST7 gene among 12 tumors with 7q-LOH. In addition, quantitative RT-PCR analyses of ST7 mRNA expression levels in 11/13 normal-tumor pairs failed to show more than a 50% decrease in tumor ST7 mRNA relative to matched normal tissues. These data suggest that LOH at 7q31-q35 is involved in the origin or progression of at least a subset of esophageal carcinomas, but that ST7 is not the target gene of this somatic event.

Adenocarcinoma↗

PubMed2003

Liquid chromatography-mass spectrometry method for the analysis of the anti-cancer agent capecitabine and its nucleoside metabolites in human plasma.

A reversed-phase high-performance liquid chromatography method with electrospray ionization and mass spectral detection is described for the determination of capecitabine, 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine in human plasma with 5-chloro-2'-deoxyuridine as the internal standard. An on-line sample clean-up procedure allows dilution of the plasma sample with the initial mobile phase. The linear dynamic range is 0.0500-10.0 microgram/ml for capecitabine, and 0.0500-25.0 microgram/ml for the metabolites, 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine, respectively. This method has been used to analyze plasma samples from patients receiving capecitabine in combination with oxaliplatin.

Antimetabolites, Antineoplastic↗

PubMed2003

Effect of levodopa chronic administration on behavioral changes and fos expression in basal ganglia in rat model of PD.

To study behavioral character and changes of neuronal activity in the basal ganglia of rat model of levodopa-induced dyskinesia, unilateral 6-hydroxydopamine lesioned rat model of Parkinson disease (PD) was treated with levodopa/benserazide twice daily for 4 weeks and the behavior observed on the 1st, 3rd, 4th, 7th, 9th, 10th, 14th, 21st and 28th day. The animals were sacrificed and immunohistochemical technique was used to measure the changes of Fos expression in the caudate putamen (CPU), globus pallidus (GP) and sensorimotor area of cerebral cortex 2 h after the last treatment. The results showed that pulsatile treatment with a subthreshold dose of levodopa gradually induced abnormal involuntary movement (AIM), including stereotypy (limb dyskinesia, axial dystonia and masticatory dyskinesia) towards the side contralateral to the dopamine-denervated striatum and increased contraversive rotation. The motor pattern of each subtype was highly stereotypic across individual rats, and the proportion of each subtype was not consistent among individual rats. Fos positive nuclei in the CPU and GP were increased by levodopa acute administration, and more remarkably in the CPU, but not in the cerebral cortex. After repeated levodopa treatment. Fos positive nuclei were reduced remarkably in the CPU, but were increased in the GP and cerebral cortex. It was concluded that the neural mechanisms underlying levodopa induced AIM in rat model of PD was very similar to those seen in levodopa-induced dyskinesia (LID) in PD patients and MPTP-lesioned monkeys, and increased striatopallidal neuronal activity might be involved in occurrence of LID.

Animals↗

PubMed2003

Impact of flexor digitorum superficialis on gliding function of the flexor digitorum profundus according to regions in zone II.

PURPOSE: Structures and gliding characteristics of the flexor tendons vary remarkably according to regions of zone II in the hand. We studied the impact of the flexor digitorum superficialis (FDS) on the work of flexion and excursion efficiency of the flexor digitorum profundus (FDP) tendon in different regions of zone II. METHODS: Twenty-one fresh-frozen human fingers were used as an experimental model. The FDP was pulled to flex the finger with a tensile machine. The work of flexion of the finger and gliding excursion of the tendon were recorded in the fingers with the FDS intact, after excision of the FDS proximal to, under, or distal to the A2 pulley. RESULTS: The FDS tendon exerts notably different effects on the work of flexion and excursion efficiency of the FDP in subregions of zone II. Removal of the FDS under the A2 pulley affected the FDP most manifestly, causing a 12% decrease in the work of flexion and a loss of the excursion efficiency at the metacarpophalangeal joint. Removal of the FDS proximal to the A2 pulley had a less notable effect on the work of flexion. Removal of the FDS distal to the pulley did not markedly alter the biomechanics of the FDP. CONCLUSIONS: Removal of the FDS tendon in the area of the A2 pulley reduces the work of flexion most notably and causes a loss of excursion efficiency. Removal of the FDS tendon distal to the A2 pulley does not change the work of flexion, and removal of the FDS tendon proximal to the A2 pulley has a notable but less pronounced effect on the FDP tendon.

Aged↗

PubMed2003

Lengthening and locking: two ways to improve repair strength of obliquely lacerated tendons.

PURPOSE: Oblique transections in tendons tend to reduce the strength of conventional repairs. We evaluated the effectiveness of lengthening longitudinal strand passage and adding locking components to improve the strength. METHODS: Seventy-six fresh pig flexor tendons were transected obliquely and repaired using either a modified Kessler (grasping) repair or a locking Kessler repair. Orientations of the strands within the tendon were varied among conventional, oblique, and lengthened. The 2-mm gap formation force and ultimate strength were tested as measures of biomechanical performance for each repair. RESULTS: The 2-mm gap formation force and ultimate strength with either grasping or locking repair were the weakest with a conventional repair, stronger with an oblique repair, and the strongest with a lengthened repair. The strength was significantly greater in oblique and lengthened locking repairs than in corresponding types of the grasping repair but was not different between the repairs with conventional configurations. CONCLUSIONS: Lengthening the repairs effectively improves the repair strength in obliquely lacerated tendons, in which strength of the conventional repairs diminishes owing to a decrease in the distance from sutures' grasping points to the laceration. Adding locking components increases the strength to oblique and lengthened repairs but does not add to the repairs with locking points that are not sufficiently away from the level of laceration.

Animals↗

PubMed2003

Effects of superficialis tendon repairs on lacerated profundus tendons within or proximal to the A2 pulley: an in vivo study in chickens.

PURPOSE: In a flexor tendon injury model in chickens we undertook a study to evaluate effects of the flexor digitorum superficialis (FDS) tendon repairs on excursions, work of flexion, and adhesions of the repaired flexor digitorum profundus (FDP) tendon after their injuries within or proximal to the equivalent of the A2 pulley and early tendon motion. METHODS: Thirty-five leghorn chickens were divided into 3 groups. In group 1 the FDS and FDP tendons of the long toes on both sides were transected in the area covered by the pulley. In group 2 the tendons were transected proximal to the pulley. In the first 2 groups, both tendons were repaired on the left feet, and only the profundus was repaired with superficialis excision on the right. The operated toes underwent simulated passive flexion for 3 weeks and results were evaluated 8 weeks after surgery. Chickens in group 3 were unoperated and served as the controls. RESULTS: When the tendons were cut within the pulley the FDP excursions and work of flexion were significantly better in the toes in which the FDS was excised than in those with both tendon repairs. When they were cut proximal to the pulley the repairs of both tendons had outcomes similar to that with excision of the FDS. Adhesions were more severe when both tendons were repaired under the pulley as compared with those after repair of a single tendon. CONCLUSIONS: This study showed different effects of the surgical repair or excision of the FDS on the FDP tendon within or proximal to a major pulley. Repair of both tendons worsens the gliding of the FDP tendon and increases adhesions within the major pulley; however, repair of both tendons yields outcomes equivalent to that after repair of only the FDP tendon proximal to the pulley.

Animals↗

PubMed2003

Repair strength of tendons of varying gliding curvature: a study in a curvilinear model.

PURPOSE: This study was done to investigate changes in the strength of the repaired tendons by different curvatures of tendon motion arcs. METHOD: Forty-two fresh-frozen digital flexor tendons were divided into 4 groups and were repaired by the modified Kessler method with a running peripheral suture. The tendons were pulled over pulleys with tension at a fixed angle of 90 degrees, but radii of gliding curvature of the pulleys were set at 2.0, 1.5, and 1.0 cm in 3 groups, respectively. The tendons in the other group were subjected to linear tension. These tendons were tested in an Instron tensile machine to determine the 2-mm gap formation force and ultimate strength of the repairs. RESULTS: The 2-mm gap formation force of the tendons pulled over the curvature of a 2.0-, 1.0-, and 0.5-cm radius was, respectively, 69%, 61%, and 49% of that pulled linearly. The ultimate strength of the tendons over curvatures of 2.0-, 1.5-, and 1.0-cm radius was, respectively, 77%, 73%, and 63% of that of tendons pulled with linear tension. The gap formation force and ultimate strength were statistically the lowest in the tendons with a gliding radius of curvature of 1.0 cm. Both the gap formation force and the ultimate strength of tendon repairs decreased as the radius decreased. CONCLUSIONS: The curvature of tendon motion arcs affects the repair strength of the tendons. The findings suggest an increased likelihood of repair ruptures in the tendons that glide along curvatures over the sheaths, pulleys, or joints.

Analysis of Variance↗

PubMed2003

Tendon healing in vitro: promotion of collagen gene expression by bFGF with NF-kappaB gene activation.

PURPOSE: Matrix synthesis of intrasynovial tendon cells and activation of nuclear transcription factors are pivotal to promotion of flexor tendon healing. We investigated the effects of basic fibroblast growth factor (bFGF) on synthesis of type I collagen and activation of nuclear transcription factor kappaB (NF-kappaB) in an in vitro culture model of intrasynovial tenocytes. METHOD: Tenocytes obtained from explant culture of rabbit intrasynovial tendon segments were treated with bFGF at concentrations of 0, 2, and 10 ng/mL. Expression of type I collagen and NF-kappaB genes was determined by quantitative analysis of products of reverse-transcription polymerase chain reactions. Proliferation of the cells was assessed by incorporation of bromodeoxyuridine into the DNA of the cells. RESULTS: Expression levels of type I collagen and NF-kappaB genes of tenocytes were increased significantly by bFGF. Cell proliferation as indicated by DNA labeling was promoted significantly by bFGF. Expression of the NF-kappaB gene increased proportionately to the amounts of bFGF stimulating the cells and was correlated with increases in proliferation rate of tenocytes. CONCLUSIONS: Results of this study show that expression of type I collagen and NF-kappaB genes is promoted manifestly by bFGF. The effects were proportionate to in vitro proliferation rates of tenocytes. The study indicated that matrix synthesis of flexor tendons can be promoted by bFGF and that NF-kappaB may play a pivotal role in initiating proliferation and type I collagen synthesis of tenocytes.

Analysis of Variance↗

PubMed2003

Effects of direction of tendon lacerations on strength of tendon repairs.

PURPOSE: We compared the tensile strength of different repair configurations on tendons with oblique and transverse lacerations. METHOD: Seventy-two fresh pig flexor tendons were divided randomly and repaired using the modified Kessler, the cruciate, or the 4-strand Massachusetts General Hospital (MGH) repair methods. The tendons were lacerated either transversely or obliquely. They were repaired with conventional and oblique suture repairs. The 2-mm gap formation force and ultimate strength were determined as biomechanical performance for each repair. RESULTS: The gap formation and ultimate strength of the tendons vary with orientations of tendon lacerations and suture methods. In the tendons repaired with the modified Kessler or the cruciate methods, the 2-mm gap formation and ultimate strength of obliquely cut tendons were significantly lower than those of transversely cut tendons. The obliquely placed modified Kessler or cruciate sutures significantly improved the repair strength in the tendons with an oblique laceration. In the tendons repaired with the MGH method, no statistical differences were found in the repair strength of obliquely and transversely lacerated tendons. CONCLUSIONS: The direction of tendon lacerations affects strength of certain repair configurations. The nonlocking modified Kessler or the cruciate tendon repairs are weakened considerably when the tendon laceration is oblique but their mechanical performance is strengthened by re-orienting the repair strands to lie parallel to the laceration. The cross-locked configuration of the MGH repair is not affected by the obliquity of the tendon laceration.

Analysis of Variance↗

PubMed2003

Gp120-alum boosting of a Gag-Pol-Env DNA/MVA AIDS vaccine: poorer control of a pathogenic viral challenge.

Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by complementing antiviral cellular responses with Env antibodies. We tested this concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to macaques being primed at weeks 0 and 8 with SHIV 89.6 Gag-Pol-Env DNA and boosted at week 24 with SHIV-89.6 Gag-Pol-Env recombinant modified vaccinia Ankara (MVA). Three hundred micrograms of gp120 was delivered with the second DNA prime and the MVA booster. Eight months after vaccination, all animals were challenged intrarectally with the related, yet serologically distinct, SHIV-89.6P. The gp120 immunizations raised binding, but not neutralizing antibody for the challenge virus, and allowed testing of whether gp120 vaccines that fail to raise neutralizing antibody can improve protection. Following the second gp120 immunization, the plus-gp120 group showed >10 times higher levels of binding antibody than the minus-gp120 group. These levels fell and were overall similar in both groups at the time of challenge. Following the second challenge, both groups had similar temporal patterns and heights of binding and neutralizing antibodies. However, the plus-gp120 group had less consistent control of viremia and higher levels of plasma viral RNA for the first year postchallenge. Assays for complement-dependent enhancing antibody revealed a trend toward higher levels of activity in the plus-gp120 group. This trend did not reach significance in our animal groups of 8. We conclude that gp120 inoculations that fail to raise neutralizing antibody do not improve the efficacy of Gag-Pol-Env DNA/MVA vaccines.

AIDS Vaccines↗

PubMed2003

Peripheral blood Dendritic cells are not a major reservoir for HIV type 1 in infected individuals on virally suppressive HAART.

Dendritic cells (DCs) are potent antigen-presenting cells, and their physiological localization in tissues that interact with the external environment is important as a first barrier against pathogens such as human immunodeficiency virus type I (HIV-1). Several models have been proposed to explain the possible role of DCs as a reservoir for HIV-1 in patients on virally suppressive highly active antiretroviral therapy (HAART). However, the low yield of cell isolates has made this evaluation a difficult task. The present study analyzes whether peripheral blood DCs from HIV-1-infected individuals on virally suppressive HAART, with plasma HIV-1 RNA levels of less than 50 copies/ml, carry either HIV-1 provirus and/or HIV-1 virions. Peripheral blood DCs were isolated from a cohort of 10 HIV-1-seropositive men taking suppressive HAART. In five patients, plasmacytoid and myeloid dendritic cells were isolated to attempt to identify their respective roles in HIV-1 residual disease. Viral out-growth assays were performed in vitro, as well as gag and R/U5 polymerase chain reaction (PCR) amplification of viral RNA and DNA, respectively, from DC and peripheral blood mononuclear cell (PBMC) extracts. Fluorescence activated cell-sorting (FACS) data revealed cellular yields from 85.90 to 95.18%, of relatively pure DCs isolated from patients' PBMCs. Although HIV-1 RNA gag and DNA RU/5 were detected in all PBMC samples isolated from the patients, proviral DNA and viral RNA forms were not detected in any of the DC isolates. In addition, no replication-competent virus was demonstrated in DC coculture assays, while virus was isolated from each patients' CD8+ T-lymphocyte-depleted PBMC cocultures. Furthermore, HIV-1 gag proviral DNA was not detected in either plasmacytoid or myeloid DC subfractions. The current study suggests that in HIV-1-infected individuals treated with suppressive HAART, peripheral blood DCs do not carry HIV-1 proviral DNA or viral particles attached to their surface. These populations of peripheral blood DCs are likely not a major HIV-1 reservoir in patients on HAART with clinically undetectable plasma viral RNA.

Anti-HIV Agents↗

PubMed2003

Towards artificial repair of UV-damaged DNA: studies on drug binding and alkali hydrolysis.

Properties of the DNA containing the (6-4) photoproduct, one of the major UV-induced lesions, were analyzed. Two basic studies towards artificial recognition and repair of this type of damaged DNA are presented here. One is recognition of the UV-damaged DNA by a minor groove-binding drug. It was found by CD spectroscopy that distamycin could bind DNA duplexes containing the (6-4) photoproduct as effectively as the unmodified DNA, whereas a DNA duplex containing the cyclobutane pyrimidine dimer was not recognized by this drug. The other is a mechanistic study on alkali degradation of this photoproduct. HPLC and NMR analyses revealed that hydrolysis between the N3 and C4 positions of the 5' pyrimidine component occurred first. This intermediate was relatively stable, and further degradation to the strand break required severe conditions like the hot piperidine treatment.

Alkalies↗

PubMed2003

Photoreactivity of 5-iodouracil-containing telomeric DNA.

The photoreaction of 5-iodouracil-((I)U)-containing telomeric oligonucleotides in parallel or antiparallel structures, generated in the presence of K+ or Na+ ions, was investigated. It was found that the photoreactivity of telomeric DNA depends on the differences in the quadruplex conformations in the presence of K+ or Na+ ions.

Base Sequence↗

PubMed2003

Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors.

The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.

Activin Receptors, Type II↗

PubMed2003

Deferoxamine improves early postresuscitation reperfusion after prolonged cardiac arrest in rats.

The no-reflow phenomenon and delayed hypoperfusion after transient cardiac arrest (CA) impede postischemic recovery. Activation of lipid peroxidation (LPO) after ischemia and reperfusion is considered one of the mechanisms responsible for such abnormalities. The present study investigates the influence of iron-dependent LPO inhibitor deferoxamine (DFO) on the cerebral perfusion after prolonged CA and resuscitation. Fourteen male Sprague-Dawley rats were subjected to 17 minutes of CA, induced by esmolol (an ultrashort-acting beta-blocker) and apnea, followed by resuscitation by retrograde intraaortic infusion of oxygenated donor blood mixed with a resuscitation cocktail inside a vertical-bore 9.4-T magnetic resonance imaging (MRI) magnet. Animals were randomized double-blindly into two groups to receive DFO or saline, respectively. Cerebral perfusion was measured by MRI continuously using the arterial spin-labeling method before, during, and after CA. All animals were successfully resuscitated in 1.36 +/- 0.04 minutes with well-controlled arrest time (17.99 +/- 0.03 minutes) in both groups. Deferoxamine significantly increased cerebral perfusion in hippocampus, thalamus, hypothalamus, and amygdala, but not in cortex, during the first 20 minutes of reperfusion. In the DFO-treated group, the neurologic deficit score was significantly better (400 +/- 30 vs. 250 +/- 47, out of 500 as the best, P < 0.05) and weight loss was significantly less (33 +/- 6 vs. 71 +/- 19 g, P < 0.05) 5 d after arrest. The finding supports the notion that early reperfusion immediately after resuscitation is important for long-term outcome and that LPO may be involved in microvascular disorders during the reperfusion, particularly in the brain after prolonged cardiac arrest and resuscitation.

Animals↗

PubMed2003

In a subset of subjects on highly active antiretroviral therapy, human immunodeficiency virus type 1 RNA in plasma decays from 50 to <5 copies per milliliter, with a half-life of 6 months.

Three of five virally suppressed human immunodeficiency virus type I (HIV-1)-infected patients treated with highly active antiretroviral therapy and followed intensively with a supersensitive reverse transcriptase PCR assay with a lower limit of quantitation of 5 copies/ml showed statistically significant viral load decays below 50 copies/ml, with half-lives of 5 to 8 months and a mean of 6 months. This range of half-lives is consistent with the estimated half-life of the latent HIV-1 reservoir in the peripheral blood. Those patients without decay of viral load in plasma may have significant cryptic HIV-1 residual replication.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Unfolding the pathophysiological role of bioactive lysophospholipids.

Lysophospholipids (LPLs), including glycerol- and sphingoid-based lipids, stimulate cell signaling and play important pathophysiological roles in humans and other animals. These LPLs include lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC). Analyses of LPLs in human body fluids from subjects with different pathophysiological conditions reveal not only the relevance of LPLs in human diseases, but also their potential application as biomarkers and/or therapeutic targets. In recent years, the identification and/or characterization of the plasma membrane receptors for LPLs and enzymes regulating the metabolism of LPLs have greatly facilitated our understanding of their role and signaling properties. In vitro and in vivo functional and signaling studies have revealed the broad and potent biological effects of LPLs and the mechanisms of LPL actions in different cellular systems. Development of specific antagonists for each of the LPL receptors will provide powerful tools for dissecting signaling pathways mediated by receptor subtypes. More importantly, these antagonists may serve as therapeutics for relevant diseases. Genetic depletion of LPL receptors in mice has provided and will continue to provide critical information on the pathophysiological roles of LPL receptors. It is important to further evaluate the significance of targeting these bioactive LPL receptors, their downstream signaling molecules, and/or metabolic enzymes in the treatment of cancers and other diseases.

Animals↗

PubMed2003

Purification of glucose-6-phosphate dehydrogenase from baker's yeast in aqueous two-phase systems with free triazine dyes as affinity ligands.

To improve the selectivity of glucose-6-phosphate dehydrogenase (G6PDH) extraction by an aqueous two-phase system, a simple and inexpensive affinity aqueous two-phase system using unbound reactive triazine dyes as ligands was introduced. In a polyethylene glycol (PEG)/hydroxypropyl starch (PES) system, the unbound free triazine dyes, Cibacron Blue F3GA and Procion Red HE3B, partitioned unevenly in the top PEG-rich phase and thus showed an affinity effect on G6PDH, but no influence on hexokinase. The various parameters investigated were pH of the system, buffers, molecular weight of PEG, and ligand type and concentration. A two-step affinity extraction process was established for the purification of G6PDH from baker's yeast. The total yield of G6PDH was 66.9% and purification factor was 2.35.

Chromatography, Affinity↗