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Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 163 records · Page 9Linked to original sources
PubMed2001

Interaction of morin-cetyltrimethylammonium bromide with nucleic acids and determination of nucleic acids at nanograms per milliliter levels based on the enhancement of preresonance light scattering.

A new preresonance light scattering (PRLS) assay of nucleic acids is presented. At pH 7.30, the weak PRLS of morin-cetyltrimethylammonium bromide (CTMAB) can be greatly enhanced by the addition of nucleic acids, owing to the interaction between the nucleic acid and morin-CTMAB. After the addition of morin and CTMAB to DNA, the zeta potential of DNA decreases and changes from negative to positive, which is due to the formation of an associate, the aggregation of morin on nucleic acids and the electric neutralization between DNA and the cationic surfactant CTMAB. Mechanism studies showed that the enhanced PRLS comes from the aggregation of morin in the presence of nucleic acids and CTMAB. The enhanced intensity of PRLS is in proportion to the concentration of nucleic acids in the range 7.5 x 10(-9)-1.0 x 10(-5) g ml(-1) for calf thymus DNA, 7.5 x 10(-9)-1.0 x 10(-6) g ml(-1) for salmon sperm DNA and 1.0 x 10(-8)-1.0 x 10(-6) g ml(-1) for yeast RNA. The detection limits are 3.4, 6.2 and 4.1 ng ml(-1) for calf thymus DNA, salmon sperm DNA and yeast RNA, respectively. Synthetic samples were analyzed satisfactorily.

Animals↗
PubMed2001

A global optimization method for three-dimensional conformal radiotherapy treatment planning.

Multiple local minima exist in almost every coplanar or non-coplanar radiotherapy treatment planning problem. We used a global optimization method based on topographical information about the distribution of local minima to find all local minima and select the best as the global minimum. We uniformly select N random points from search regions and construct a topographical graph, from which M (M << N) starting points are selected to launch a local search. Because every seed point was at or near the local minimum, the solutions found by the local search could be used as the final optimization results. We verified this algorithm by applying it to three different clinical cases and comparing the results with those obtained by a local optimization method (sequential quadratic programming). The results show that this algorithm is feasible and efficient.

Algorithms↗
PubMed2001

An optimization method for importance factors and beam weights based on genetic algorithms for radiotherapy treatment planning.

We propose a new method for selecting importance factors (for regions of interest like organs at risk) used to plan conformal radiotherapy. Importance factors, also known as weighting factors or penalty factors, are essential in determining the relative importance of multiple objectives or the penalty ratios of constraints incorporated into cost functions, especially in dealing with dose optimization in radiotherapy treatment planning. Researchers usually choose importance factors on the basis of a trial-and-error process to reach a balance between all the objectives. In this study, we used a genetic algorithm and adopted a real-number encoding method to represent both beam weights and importance factors in each chromosome. The algorithm starts by optimizing the beam weights for a fixed number of iterations then modifying the importance factors for another fixed number of iterations. During the first phase, the genetic operators, such as crossover and mutation, are carried out only on beam weights, and importance factors for each chromosome are not changed or 'frozen'. In the second phase, the situation is reversed: the beam weights are 'frozen' and the importance factors are changed after crossover and mutation. Through alternation of these two phases, both beam weights and importance factors are adjusted according to a fitness function that describes the conformity of dose distribution in planning target volume and dose-tolerance constraints in organs at risk. Those chromosomes with better fitness are passed into the next generation, showing that they have a better combination of beam weights and importance factors. Although the ranges of the importance factors should be set in advance by using this algorithm, it is much more convenient than selecting specific numbers for importance factors. Three clinical examples are presented and compared with manual plans to verify this method. Three-dimensional standard displays and dose-volume histograms are shown to demonstrate that this method is feasible, automatic and convenient.

Abdominal Neoplasms↗
PubMed2001

Verification of the super-omni wedge concept.

This study verifies the concept of the super-omni wedge by validating its equations for effective wedge orientation and wedge angle and by comparing the dose distributions it produces with those produced by other wedge techniques. To validate the equations, we calculated dose distributions for 20 combinations of wedge orientations and wedge angles: we then determined the differences between the wedge orientations and angles predicted by the equations and those calculated by a three-dimensional treatment-planning system. To compare the super-omni wedge concept with other techniques, we calculated the dose and position differences between the dose distributions produced by the super-omni wedge concept and those produced by other wedge techniques. The error of wedge orientations ranged from -0.5 degrees to 0.4 degrees, and that of wedge angles ranged from -0.6 degrees to 1.7 degrees. The dose distributions produced by the super-omni wedge were similar and therefore equivalent to those produced by other wedge techniques. Serving as an intermediate step in treatment-planning optimization. the super-omni wedge is a reliable method for producing wedged dose distributions with arbitrary wedge orientations and wedge angles.

Algorithms↗
PubMed2001

Muristerone A-induced nerve growth factor release from genetically engineered human dermal fibroblasts for peripheral nerve tissue engineering.

In this study, human dermal fibroblasts (hDFBs) were genetically modified to release human nerve growth factor (NGF) using an ecdysone-inducible system. NGF cDNA was inserted into the pIND vector and then hDFBs were cotransfected with pIND-NGF and pVgRXR. Muristerone A, an analog of ecdysone, was used as the inducing agent. NGF release from transfected hDFBs was assessed in vitro and in vivo. Transfected hDFBs in the presence of Muristerone A possessed a maximal in vitro release of 8.5 +/- 0.4 pg of NGF/mL per 10(3) cells, demonstrating significantly higher NGF levels compared to control hDFBs. The in vitro release rate curve for transfected hDFBs in the presence of Muristerone A exhibited a maximum of 5.1 +/- 0.2 ng NGF/10(6) cells/day. A PC-12 bioassay demonstrated that the in vitro NGF released is bioactive. When transfected hDFBs in the presence of Muristerone A were placed in vivo in nude rats, NGF levels reach 2074 +/- 257 pg/mL and 1620 +/- 132 pg/mL at 24 and 48 h, respectively. These levels were significantly higher than negative control and wound fluid levels. Results support further in vivo investigation of this molecular "on" switch for peripheral nerve regeneration.

Animals↗
PubMed2001

Loss of mitochondrial DNA in rabbit bladder smooth muscle following partial outlet obstruction results from lack of organellar DNA replication.

When the rabbit bladder outlet is partially obstructed, the relative amount of mitochondrial (mt) DNA per cell in bladder smooth muscle falls rapidly. In order to assess whether this loss of organellar genome results from attenuation of mt DNA replication, we cloned portions of rabbit genes specifying the single-strand binding (SSB) protein required for initiation of mt DNA replication, and the catalytic subunit of DNA polymerase gamma (pol gamma), the replication enzyme itself. We then designed primer-probe systems for real-time RT-PCR (TaqMan) analyses for each gene. These were used to assess mRNA in preparations from bladder smooth muscle and mucosa from rabbits subjected to surgical obstruction of the bladder outlet for up to 14 days. mRNA from the pol gamma gene remained essentially at control level in smooth muscle and mucosa in all samples. In mucosa, mRNA from the SSB protein gene remained virtually at control levels in all samples, as did mt genome copy number. In smooth muscle, however, levels of this mRNA declined by >95% within 3 days of obstruction and remained at that level through 14 days; this attenuation of SSB protein mRNA paralleled the loss of mt DNA in the same smooth muscle samples. Thus, lack of mt SSB protein, and consequently attenuated mt DNA replication, is a primary factor in the loss of mt genome copies in bladder smooth muscle after outlet obstruction in the rabbit model of benign bladder dysfunction.

Animals↗
PubMed2001

The NH(2)-terminus of norepinephrine transporter contains a basolateral localization signal for epithelial cells.

When expressed in epithelial cells, dopamine transporter (DAT) was detected predominantly in the apical plasma membrane, whereas norepinephrine transporter (NET) was found in the basolateral membrane, despite 67% overall amino acid sequence identity. To identify possible localization signals responsible for this difference, DAT-NET chimeras were expressed in MDCK cells and localized by immunocytochemistry and transport assays. The results suggested that localization of these transporters in MDCK cells depends on their highly divergent NH(2)-terminal regions. Deletion of the first 58 amino acids of DAT (preceding TM1) did not change its apical localization. However, the replacement of that region with corresponding sequence from NET resulted in localization of the chimeric protein to the basolateral membrane, suggesting that the NH(2)-terminus of NET, which contains two dileucine motifs, contains a basolateral localization signal. Mutation of these leucines to alanines in the context of a basolaterally localized NET/DAT chimera restored transporter localization to the apical membrane, indicating that the dileucine motifs are critical to the basolateral localization signal embodied within the NET NH(2)-terminal region. However, the same mutation in the context of wild-type NET did not disrupt basolateral localization, indicating the presence of additional signals in NET directing its basolateral localization within the plasma membrane.

Amino Acid Sequence↗
PubMed2001

The association of microsomal epoxide hydrolase polymorphisms and lung cancer risk in African-Americans and Mexican-Americans.

This study evaluated the influence of genetic polymorphisms in the microsomal epoxide hydrolase (mEPHX) gene on lung cancer risk in a case-control study of two different ethnic groups, Mexican-Americans and African-Americans. There were 138 lung cancer cases (60 Mexican-American and 78 African-American) and 148 controls (76 Mexican-American and 72 African-American). There was a significant difference in the distribution of the mEPHX exon 4 polymorphism between the two ethnic groups with African-Americans more likely to be heterozygous and Mexican-Americans to be wild-type. There was no significant difference between the ethnic groups for the allelic distribution of the mEPHX exon 3 polymorphism. When the exon 4 and exon 3 polymorphism distributions in cases and controls were examined by ethnicity, only the Mexican-American cases showed a substantial proportion with the exon 4 polymorphism. The exon 4 polymorphism was associated with a significantly increased risk of lung cancer only among the Mexican-American cases (adjusted OR 3.6, 95% CI 1.26, 10.42). Younger Mexican-Americans with the exon 4 polymorphism had a greater risk of lung cancer than older members of their groups (adjusted OR 7.4, 95% CI 1.36, 40.23; 1.6, 95% CI 0.33, 7.80, respectively). The exon 3 polymorphism did not appear to significantly increase the risk of lung cancer in all but one study group examined. Mexican-Americans younger than 65 years did demonstrate an elevated risk of lung cancer (adjusted OR 4.6, 95% CI 1.19, 17.56). However, no statistically significant risk was observed in the African-American study groups for both exon 3 and exon 4 polymorphisms. These findings suggest that the presence of the exon 4 and exon 3 polymorphisms of mEPHX may be associated with an increased risk of lung cancer particularly among younger Mexican-Americans in this study.

Aged↗
PubMed2001

Expression and hypoxic regulation of angiopoietins in human astrocytomas.

Vascular endothelial growth factor (VEGF) is a major inducer of tumor angiogenesis and edema in human astrocytomas by its interaction with cognate endothelial-specific receptors (VEGFR1/R2). Tie1 and Tie2/Tek are more recently identified endothelial-specific receptors, with angiopoietins being ligands for the latter. These angiogenic factors and receptors are crucial for the maturation of the vascular system, but their role in tumor angiogenesis, particularly in astrocytomas, is unknown. In this study, we demonstrate that the angiopoietin family member Ang1 is expressed by some of the astrocytoma cell lines. In contrast to VEGF, Ang1 is down regulated by hypoxia. Ang2 was not overexpressed. Expression profiles of low-grade astrocytoma specimens were similar to those of normal brain, with low levels of Ang1, Ang2, and VEGF expression. Glioblastoma multiforme expressed higher levels of Angl, but not to the same degree as pseudopalisading astrocytoma cells around necrotic and hypoxic zones expressed VEGF, as shown in previous studies. Ang2 expression in the highly proliferative tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek. The expression profile of these angiogenic factors and their endothelial cell receptors in human glioblastomas multiforme was similar to that in a transgenic mouse model of glioblastoma multiforme. These data suggest that both VEGF and angiopoietins are involved in regulating tumor angiogenesis in human astrocytomas.

Angiopoietin-1↗
PubMed2001

Intraperitoneal, but not enteric, adenosine administration improves survival after volume-controlled hemorrhagic shock in rats.

OBJECTIVE: To circumvent the potential adverse systemic side effects of adenosine, this study explored the potential benefit of intraperitoneal or enteric adenosine on survival and inflammatory responses after volume-controlled hemorrhagic shock. DESIGN: Prospective, randomized, and blinded. A three-phase, volume-controlled hemorrhagic shock model was used: hemorrhagic shock phase (120 mins), resuscitation phase (60 mins), and observation phase (72 hrs). Three groups were compared: controls, intraperitoneal adenosine, and enteric adenosine. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Starting at 20 mins of hemorrhagic shock and continuing through the resuscitation phase, all three groups received both intraperitoneal lavage and repeated bolus injections into the ileum of vehicle (normal saline) or adenosine. In the intraperitoneal adenosine group (n = 10), adenosine solution (0.1 mM) was used for intraperitoneal lavage. In the enteric adenosine group (n = 10), adenosine (1.0 mM) was injected into the ileum. Blood cytokine concentrations and leukocyte infiltration in lungs and liver were studied in 12 separate rats (control and intraperitoneal adenosine, n = 6 each) with the same hemorrhagic shock model at resuscitation time 1 hr or 4 hrs. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and heart rate were similar between the three groups during hemorrhagic shock and resuscitation. Potassium, lactate, and blood urea nitrogen concentrations were lower and arterial pH was higher in the intraperitoneal and enteric adenosine groups compared with the control group (both p <.05). Survival time to 72 hrs was longer in the intraperitoneal adenosine group than in the control group(p <.05). Neither plasma interleukin-1beta, interleukin-6, interleukin-10, and tumor necrosis factor-alpha concentrations nor leukocyte infiltration in the lungs and liver was different between the control and intraperitoneal adenosine groups. CONCLUSIONS: The administration of adenosine via the intraperitoneal route improves survival time after severe volume-controlled hemorrhagic shock in rats without worsening hypotension or bradycardia. This beneficial effect may not be attributable to effects of adenosine on the inflammatory response.

Adenosine↗
PubMed2001

Effect of potassium supplementation on blood pressure in Chinese: a randomized, placebo-controlled trial.

OBJECTIVE: To examine the effect of potassium supplementation on blood pressure (BP) in a Chinese population who consume a habitual high sodium and low potassium diet. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community sample from Beijing, China. PARTICIPANTS: A total of 150 men and women aged 35-64 years with an initial systolic BP 130-159 mmHg and/or diastolic BP 80-94 mmHg. INTERVENTIONS: Participants were randomly assigned to take 60 mmol potassium chloride supplement or placebo for 12 weeks. MAIN OUTCOME MEASURE(S): BP measurements were obtained at baseline, and at 6 weeks and 12 weeks during the trial, using random-zero sphygmomanometers. RESULTS: The average baseline urinary excretion of sodium and potassium was 182 mmol/24 h and 36 mmol/24 h. Baseline BP and other measured variables were similar between the potassium supplementation and placebo groups. In the active compared to the placebo treatment group, the urinary excretion of potassium was significantly increased by 20.6 mmol/24 h (P< 0.001) during 12 weeks of intervention. Compared to placebo, active treatment was associated with a significant reduction in systolic BP (-5.00 mmHg, 95% CI: -2.13 to -7.88 mmHg, P < 0.001) but not diastolic BP (-0.63 mmHg, 95% CI: -2.49 to1.23 mmHg, P = 0.51) during 12-week intervention. CONCLUSION: These data indicate that moderate potassium supplementation resulted in a substantial reduction in systolic BP. Our findings suggest that increased potassium intake may play an important role in the prevention and treatment of hypertension in China.

Adult↗
PubMed2001

Gut damage during hemorrhagic shock: effects on survival of oral or enteral interleukin-6.

It has been reported that oral interleukin (IL)-6, without deleterious systemic side effects, prevents bacteremia and gut epithelial apoptosis after hemorrhagic shock (HS) in rodents. The goal of this study was to explore potential benefit of oral or enteral IL-6 on the gut and, consequently, on survival in a long-term outcome model of HS in rats. In Study A, 20 rats (control and IL-6, n = 10 per group) were anesthetized by spontaneous breathing of halothane and N2O. The left femoral vein and artery were cannulated. HS was initiated with withdrawal of 3 mL of blood per 100 g body weight over 15 min, and mean arterial pressure was maintained at 40 to 50 mmHg for another 75 min (total HS 90 min) by blood withdrawal or infusion of Ringer's solution. At HS 90 min, resuscitation included reinfusion of shed blood and additional Ringer's solution to restore normotension for 30 min. After awakening at resuscitation time 30 min, the rats received either 300 units IL-6 or the same volume of vehicle (controls) injected into the stomach via a feeding cannula. In Study B, 20 rats (control and IL-6, n = 10 per group), fasted overnight, were prepared and treated as in Study A, except that HS was initiated with withdrawal of 2 mL blood per 100 g over 10 min, and mean arterial pressure was maintained at 35-40 mmHg. IL-6 rats received 3,000 units IL-6 in 5 mL of normal saline injected directly into the ileum lumen 20 min after induction of shock and again at resuscitation time 60 min. Control rats received normal saline alone. In both studies, survival was observed to 72 h. In Study A, 7 of 10 rats in the control group and 5 of 10 in the IL-6 group survived to 72 h (NS). Macroscopic assessment of gut injury was not different between the two groups. In Study B, 6 of 10 rats survived to 72 h in each group. Frequency of bacteria growth in liver tissue of 72 h survivors was not different between the two groups. IL-6, administered into the stomach or directly injected into the small intestine lumen, did not protect the gut from ischemic injury, nor did it improve survival following severe HS in rats.

Administration, Oral↗
PubMed2001

Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium.

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 micrograms/g creatinine. The findings were similar to those for excess urinary secretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.

Acetylglucosaminidase↗
PubMed2001

A maximum-entropy method for the planning of conformal radiotherapy.

The maximum entropy method (MEM) is a powerful inverse analysis technique that is used in many fields of science and engineering to perform tasks such as image reconstruction and processing of nuclear magnetic resonance signals. Unlike other methods, MEM naturally incorporates a priori knowledge of the problem into the optimized cost function. This feature is especially important in radiotherapy planning, because some knowledge is usually available about the stage of tumor development and about the prescription doses, including some dose constraints to the surrounding normal organs. Inverse planning is inherently consistent with the ability of MEM to estimate parameters inversely. In this investigation, an entropy function determines the homogeneity of dose distribution in the planning target volume; a least-squares function is added to the maximum entropy function as a constraint to measure the quality of reconstructed doses in organs at risk; and an iterative Newton-Ralphson algorithm searches for the optimization solution. Here we provide two examples that validate this application of MEM and the results were compared with manual plans. Although the examples involve conformal radiotherapy, we think MEM can be adopted to optimize intensity-modulated radiation therapy.

Algorithms↗
PubMed2001

Moloney murine leukemia virus integrase protein augments viral DNA synthesis in infected cells.

Mutations in the IN domain of retroviral DNA may affect multiple steps of the virus life cycle, suggesting that the IN protein may have other functions in addition to its integration function. We previously reported that the human immunodeficiency virus type 1 IN protein is required for efficient viral DNA synthesis and that this function requires specific interaction with other viral components but not enzyme (integration) activity. In this report, we characterized the structure and function of the Moloney murine leukemia virus (MLV) IN protein in viral DNA synthesis. Using an MLV vector containing green fluorescent protein as a sensitive reporter for virus infection, we found that mutations in either the catalytic triad (D184A) or the HHCC motif (H61A) reduced infectivity by approximately 1,000-fold. Mutations that deleted the entire IN (DeltaIN) or 34 C-terminal amino acid residues (Delta34) were more severely defective, with infectivity levels consistently reduced by 10,000-fold. Immunoblot analysis indicated that these mutants were similar to wild-type MLV with respect to virion production and proteolytic processing of the Gag and Pol precursor proteins. Using semiquantitative PCR to analyze viral cDNA synthesis in infected cells, we found the Delta34 and DeltaIN mutants to be markedly impaired while the D184A and H61A mutants synthesized cDNA at levels similar to the wild type. The DNA synthesis defect was rescued by complementing the Delta34 and DeltaIN mutants in trans with either wild-type IN or the D184A mutant IN, provided as a Gag-IN fusion protein. However, the DNA synthesis defect of DeltaIN mutant virions could not be complemented with the Delta34 IN mutant. Taken together, these analyses strongly suggested that the MLV IN protein itself is required for efficient viral DNA synthesis and that this function may be conserved among other retroviruses.

Base Sequence↗