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Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 307 records · Page 17Linked to original sources

Selection and determination of beam weights based on genetic algorithms for conformal radiotherapy treatment planning.

A genetic algorithm has been used to optimize the selection of beam weights for external beam three-dimensional conformal radiotherapy treatment planning. A fitness function is defined, which includes a difference function to achieve a least-square fit to doses at preselected points in a planning target volume, and a penalty item to constrain the maximum allowable doses delivered to critical organs. Adjustment between the dose uniformity within the target volume and the dose constraint to the critical structures can be achieved by varying the beam weight variables in the fitness function. A floating-point encoding schema and several operators, like uniform crossover, arithmetical crossover, geometrical crossover, Gaussian mutation and uniform mutation, have been used to evolve the population. Three different cases were used to verify the correctness of the algorithm and quality assessment based on dose-volume histograms and three-dimensional dose distributions were given. The results indicate that the genetic algorithm presented here has considerable potential.

Adolescent↗

Comparison of electrocardiographic findings between Northern and Southern Chinese population samples.

BACKGROUND: Cardiovascular disease is rare in China, but there are few data on the prevalence of electrocardiographic (ECG) abnormalities in Chinese populations. METHODS: The ECG surveys were carried out in four Chinese population samples, in a total of 9,666 adults aged 35-54 in Beijing and Guangzhou, China from 1981 to 1984. Twelve-lead resting ECG tracings were coded by the Minnesota Code. RESULTS: Prevalence per 1,000 of abnormal ECG ranged from 77.4 to 209.8, and was higher for men than women and higher for Guangzhou than Beijing. Prevalence per 1,000 of major abnormalities in Guangzhou was 29.8 for men and 78.4 for women, higher than the 18.4 and 29.6 for counterparts in Beijing. The ECG changes attributed in 'Western' populations to coronary heart disease (CHD), such as large Q waves (Minnesota Code 1-1, 1-2) and ST-T abnormalities, were similar between Beijing and Guangzhou men, but Guangzhou women had much higher prevalence of ST-T abnormalities than Beijing women. Other ECG abnormalities such as A-V block, left branch bundle block, and left ventricular hypertrophy were rare in people of both sites. CONCLUSIONS: Compared with similar data from the US, these Chinese populations had a relatively low prevalence of ECG abnormalities putatively related to CHD. This corresponds with the low incidence of CHD in the Chinese population. However, within the Chinese populations of this study, a high abnormality rate appeared in a population with low incidence of CHD and hypertension (Guangzhou women). Reasons why ECG abnormalities do not parallel prevalence levels of CHD and hypertension remain to be elucidated.

Adult↗

Competence of the internal jugular vein valve is damaged by cannulation and catheterization of the internal jugular vein.

BACKGROUND: Experimental results suggest that the competence of the internal jugular vein (IJV) valve may be damaged when the IJV is cannulated for insertion of a central venous catheter. It has further been hypothesized that the risk of causing incompetence of the proximally located valve might be reduced by using a more distal site for venous cannulation. The present study evaluated these hypotheses in surgical patients. METHODS: Ninety-one patients without preexisting incompetence of the IJV valve were randomly assigned to undergo distal or proximal IJV cannulation (> or = 1 cm above or below the cricoid level, respectively). Color Doppler ultrasound was used to study whether new valvular incompetence was present during Valsalva maneuvers after insertion of a central venous catheter, immediately after removal of the catheter, and, in a subset of patients, several months after catheter removal, when compared with baseline findings before cannulation of the IJV. RESULTS: Incompetence of the IJV valve was frequently induced both by proximal and distal cannulation and catheterization of the IJV. Its incidence was higher after proximal than after distal cannulation (76% vs. 41%; P < 0.01) and tended to be so after removal of the catheter (47% vs. 28%; P = 0.07). Valvular incompetence persisting immediately after removal of the catheter did not recover within 8-27 months in most cases. CONCLUSIONS: Cannulation and catheterization of the IJV may cause persistent incompetence of the IJV valve. Choosing a more distal site for venous cannulation may slightly lower the risk of causing valvular incompetence but does not reliably avoid it.

Catheterization, Central Venous↗

Radiation therapy for local control of eyelid sebaceous cell carcinoma: report of two cases and review of the literature.

PURPOSE: Because of previous reports of increased rate of recurrence and mortality after radiation therapy, eyelid sebaceous cell carcinoma has been considered radioresistant. Recent reports of success with primary radiation therapy have been attributed to advancements in irradiating technology and technique. Two cases of eyelid sebaceous cell carcinoma successfully treated with radiation therapy are reported. The techniques used are compared with the techniques described in previous reports, and factors favoring successful treatment are reevaluated. METHODS: Case series and review of the literature. Two cases of eyelid sebaceous cell carcinoma that underwent radiation therapy are described. Both patients were offered, but refused, surgical excision. One patient received 69 Gy combined superficial and megavoltage x-ray irradiation to the left lower eyelid. The second patient received 59 Gy megavoltage electron beam irradiation to the right upper eyelid. A review of the literature was performed, and Fisher's exact test analysis was used to compare the results of all reported cases treated with < or =55 Gy with those treated with >55 Gy. RESULTS: In both cases, the tumor responded to radiation therapy. One patient died 39 months after treatment, of myocardial infarction. The second patient is without clinical evidence of tumor recurrence 46 months after treatment. Fisher's exact test showed an advantage to patients treated with >55 Gy radiation (p = 0.05). CONCLUSION: Radiation therapy with an appropriate delivery system is effective as a curative treatment for eyelid sebaceous cell carcinoma when >55 Gy of radiation dose is delivered. It should be considered for patients seeking an alternative to surgical excision.

Adenocarcinoma, Sebaceous↗

Renal vascular morphology and haemodynamics in Dahl salt-sensitive rats on high salt-low potassium diet: neural and genetic influences.

OBJECTIVE: A dietary combination of high salt and low potassium (HS-LK) exacerbates hypertension in Dahl salt-sensitive (DS) rats and renders Dahl salt-resistant (DR) rats hypertensive. In both strains, the hypertension is accompanied by remodelling of the renal resistance vasculature, and is attenuated by peripheral chemical sympathectomy. In the current study, we sought to determine whether the sympathetic nervous system is causally involved in mediating the renal vascular and haemodynamic alterations associated with HS-LK feeding in Dahl rats. DESIGN: Two groups each of DS and DR rats were maintained on HS-LK diet (8% NaCl, 0.2% KCl) for 8 weeks. One group of DS (n = 9) and DR (n = 8) were treated with 6-hydroxydopamine (6-OHDA) in 0.001 N HCl vehicle to chemically ablate peripheral sympathetic nerve terminals. The two remaining groups (n = 8 each) received equivalent injections of vehicle. METHODS: At the end of the dietary regimen, arterial blood pressure (ABP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and the structure of intra-renal resistance vessels was examined by planar morphometric analysis of coronal sections prepared from perfusion-fixed kidneys. RESULTS: Both 6-OHDA-treated and untreated DS rats presented a greater degree of intra-renal vessel remodelling characterized by reduced lumen diameter in the absence (eutrophic) or presence (hypertrophic) of cross-sectional area expansion, higher renal vascular resistance (RVR) and lower GFR and RBF than DR rats. Chemical sympathectomy increased lumen diameters and reduced vascular wall expansion, resulting in a decrease in RVR and a concomitant increase in RBF and GFR in both strains; however, the effect was more prominent in the DS rats. CONCLUSIONS: We conclude that HS-LK-induced changes in intra-renal vessel structure and renal haemodynamic function in Dahl rats are, at least in part, dependent on the activity of the sympathetic nervous system.

Animals↗

Refining the mouse chromosomal location of Cdm, the major gene associated with susceptibility to cadmium-induced testicular necrosis.

Cadmium (Cd++) is a widespread environmental pollutant and classifed as an IARC 'Category I' human carcinogen. Cd++ can also cause severe renal toxicity and may be involved clinically in cardiovascular disease and osteoporosis. Genetic differences in sensitivity to cadmium toxicity have been noted in humans, whereas, among inbred mouse strains, unequivocal genetic data exist. Resistance to cadmium-induced testicular damage was reported in 1973 to be associated with a single major recessive gene, named Cdm, which has now been localized to mouse chromosome (Chr) 3. Using polymorphic microsatellite markers and semiquantitative histological parameters, we have corroborated the original 1973 data concerning mendelian inheritance and have further refined the region containing the Cdm gene from more than 24 cM to 0.64 cM (estimated 40-80 genes). We phenotyped 26 recombinant inbred lines generated from C57BL/6J (B6, resistant) and DBA/2J (D2, sensitive) inbred mice, and determined that the Cdm gene maps between microsatellite markers D3Mit110 and D3Mit255. Although toxicity to numerous heavy metals is well known, virtually no molecular mechanisms have yet been uncovered either in humans or laboratory animals. Identification and characterization of the mouse Cdm gene should enhance our understanding of heavy metal toxicity by identifying and characterizing, for the first time, a major mammalian gene responsible for susceptibility to diseases caused by heavy metal toxicity.

Animals↗

Loss of function of a rice brassinosteroid insensitive1 homolog prevents internode elongation and bending of the lamina joint.

Brassinosteroids (BRs) are plant growth-promoting natural products required for plant growth and development. Physiological studies have demonstrated that exogenous BR, alone or in combination with auxin, enhance bending of the lamina joint of rice. However, little is known about the function of endogenous BR in rice or other grass species. We report here the phenotypical and molecular characterization of a rice dwarf mutant, d61, that is less sensitive to BR compared to the wild type. We cloned a rice gene, OsBRI1, with extensive sequence similarity to that of the Arabidopsis BRI gene, which encodes a putative BR receptor kinase. Linkage analysis showed that the OsBRI1 gene is closely linked to the d61 locus. Single nucleotide substitutions found at different sites of the d61 alleles would give rise to amino acid changes in the corresponding polypeptides. Furthermore, introduction of the entire OsBRI1 coding region, including the 5' and 3' flanking sequences, into d61 plants complemented the mutation to display the wild-type phenotype. Transgenic plants carrying the antisense strand of the OsBRI1 transcript showed similar or even more severe phenotypes than those of the d61 mutants. Our results show that OsBRI1 functions in various growth and developmental processes in rice, including (1) internode elongation, by inducing the formation of the intercalary meristem and the longitudinal elongation of internode cells; (2) bending of the lamina joint; and (3) skotomorphogenesis.

Amino Acid Sequence↗

The IgM antibody level against ganglioside GM2 correlates to the disease status of HIV-1-infected patients.

HIV-1 infection induces the expression of high level of GM2 ganglioside on infected cells and IgM antibody (Ab) against GM2 can cause complement (C)-mediated cytolysis of HIV-1-infected cells. Since GM2 is immunogenic in human, we proposed that an anti-GM2 IgM Ab may be produced by some HIV-1-infected patients and the titer of this Ab might provide some insight into the progress of the disease. On this premise, the amount of IgM Ab against GM2 was determined in 124 HIV-1-infected patients and 111 seronegative donors. As expected, the anti-GM2 IgM Ab titers of the patients was significantly higher than that of the seronegative donors while the total IgM levels remained unchanged. In addition, we determined the CD4+ cell count and the HIV-RNA load in the HIV-1-infected patients. The results showed a positive correlation between the anti-GM2 IgM Ab titer and CD4+ cell count but a negative correlation between the anti-GM2 IgM Ab titer and HIV-RNA load. These suggest that anti-GM2 IgM Ab induced and/or enhanced by HIV-1 infection causes C-mediated cytolysis of HIV-1-infected cells in vivo to a certain extent, and may help lower the plateau level of the HIV-RNA load. Therefore, the amount of IgM Ab against GM2 may be related to the prognosis of HIV-1 infected patients.

CD4 Lymphocyte Count↗

A mixed-encoding genetic algorithm with beam constraint for conformal radiotherapy treatment planning.

In this paper we propose a new hierarchical evolutionary algorithm that combines binary encoding and floating-point encoding to automatically select the beam directions and determine the weights of the selected beams. With traditional optimization methods the beam directions are fixed a priori by the operator in recognition of the fact that computer selection of beam directions is a difficult problem. In this investigation, we used a hybrid-encoding scheme. The binary encoding part of each chromosome was used to select the beam directions, and its corresponding floating-point encoding part of the same chromosome was used to determine the weights of those selected beams. Before beginning the optimization process, we set a constraint on the number of the beam directions we wanted in the final solution. We present three examples to verify this method. These examples differ with each other in tumor sites, problem sizes, and optimization parameters. Three-dimensional optimization results and statistical data showed that this method is feasible. We think this method can be easily extended to solve more complex target problems (such as nonconvex target problems).

Adolescent↗

Protection elicited by native outer membrane protein Oms66 (p66) against host-adapted Borrelia burgdorferi: conformational nature of bactericidal epitopes.

Oms66 is a Borrelia burgdorferi outer membrane porin protein whose role in Lyme disease pathogenesis and immunity has not been well established. Oms66 was solubilized from whole-cell lysates of strain B313 (which is derived from B31 but lacks OspA, -B, -C, and -D) and purified to homogeneity by fast-protein liquid chromatography. Purified native Oms66 (nOms66), which retained the ability to form large channels in a planar lipid bilayer model membrane system, and denatured Oms66 (hOms66) were used to immunize New Zealand White rabbits. The resulting Oms66 antisera were tested in a complement-dependent borreliacidal assay in parallel with basal serum and with serum from rabbits immune to reinfection with B. burgdorferi (IRS). IRS showed high-titer complement-dependent killing of both strains B31 and B313. Sera from animals immunized with nOms66 showed high-titer complement-dependent killing activity against strain B313 but exhibited no killing of B31. By comparison, serum generated from immunizations with hOms66 showed no killing activity against either strain. Following adsorption of antiserum to nOms66 with recombinant Oms66 (rOms66), the serum antibodies no longer bound to rOms66 or to nOms66 that had been denatured with 8 M urea. However, the antibodies still bound to nOms66 and killing activity against B313 was retained, thus suggesting that native, conformational epitopes are targets of this bactericidal activity. Six C3H HeJ mice were immunized with nOms66 and were challenged using "host-adapted" B. burgdorferi B31 by skin implantation of infected mouse ear tissue. Four of the six mice were protected against both localized and disseminated infection. These findings indicate that native Oms66 can elicit potent bactericidal activity and significant protective immunity against host-adapted organisms.

Adaptation, Physiological↗

Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120.

T-20 is a synthetic peptide that potently inhibits replication of human immunodeficiency virus type 1 by interfering with the transition of the transmembrane protein, gp41, to a fusion active state following interactions of the surface glycoprotein, gp120, with CD4 and coreceptor molecules displayed on the target cell surface. Although T-20 is postulated to interact with an N-terminal heptad repeat within gp41 in a trans-dominant manner, we show here that sensitivity to T-20 is strongly influenced by coreceptor specificity. When 14 T-20-naive primary isolates were analyzed for sensitivity to T-20, the mean 50% inhibitory concentration (IC(50)) for isolates that utilize CCR5 for entry (R5 viruses) was 0.8 log(10) higher than the mean IC(50) for CXCR4 (X4) isolates (P = 0. 0055). Using NL4.3-based envelope chimeras that contain combinations of envelope sequences derived from R5 and X4 viruses, we found that determinants of coreceptor specificity contained within the gp120 V3 loop modulate this sensitivity to T-20. The IC(50) for all chimeric envelope viruses containing R5 V3 sequences was 0.6 to 0.8 log(10) higher than that for viruses containing X4 V3 sequences. In addition, we confirmed that the N-terminal heptad repeat of gp41 determines the baseline sensitivity to T-20 and that the IC(50) for viruses containing GIV at amino acid residues 36 to 38 was 1.0 log(10) lower than the IC(50) for viruses containing a G-to-D substitution. The results of this study show that gp120-coreceptor interactions and the gp41 N-terminal heptad repeat independently contribute to sensitivity to T-20. These results have important implications for the therapeutic uses of T-20 as well as for unraveling the complex mechanisms of virus fusion and entry.

Anti-HIV Agents↗

Preferential incorporation of G opposite template T by the low-fidelity human DNA polymerase iota.

DNA polymerase activity is essential for replication, recombination, repair, and mutagenesis. All DNA polymerases studied so far from any biological source synthesize DNA by the Watson-Crick base-pairing rule, incorporating A, G, C, and T opposite the templates T, C, G, and A, respectively. Non-Watson-Crick base pairs would lead to mutations. In this report, we describe the ninth human DNA polymerase, Pol(iota), encoded by the RAD30B gene. We show that human Pol(iota) violates the Watson-Crick base-pairing rule opposite template T. During base selection, human Pol(iota) preferred T-G base pairing, leading to G incorporation opposite template T. The resulting T-G base pair was less efficiently extended by human Pol(iota) compared to the Watson-Crick base pairs. Consequently, DNA synthesis frequently aborted opposite template T, a property we designated the T stop. This T stop restricted human Pol(iota) to a very short stretch of DNA synthesis. Furthermore, kinetic analyses show that human Pol(iota) copies template C with extraordinarily low fidelity, misincorporating T, A, and C with unprecedented frequencies of 1/9, 1/10, and 1/11, respectively. Human Pol(iota) incorporated one nucleotide opposite a template abasic site more efficiently than opposite a template T, suggesting a role for human Pol(iota) in DNA lesion bypass. The unique features of preferential G incorporation opposite template T and T stop suggest that DNA Pol(iota) may additionally play a specialized function in human biology.

Base Pairing↗

Sequestration and inhibition of Daxx-mediated transcriptional repression by PML.

PML fuses with retinoic acid receptor alpha (RARalpha) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RARalpha, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in cells that lack PML. These data suggest that Daxx is a novel nuclear protein bearing transcriptional repressor activity that may be regulated by interaction with PML.

Adaptor Proteins, Signal Transducing↗

Functional significance of human trp1 and trp3 in store-operated Ca(2+) entry in HEK-293 cells.

The Drosophila trp (transient receptor potential) gene appears to encode the Drosophila store-operated channel (SOC), and some mammalian trp homologues have been proposed to encode mammalian SOCs. This study provides evidence for the expression of three trp homologues (Mtrp2, Mtrp3, and Mtrp4) in fibroblasts from wild-type and src knockout mice, and four trp homologues (Htrp1, Htrp3, Htrp4, and Htrp6) in human embryonic kidney (HEK-293) cells based on RT-PCR techniques. In HEK-293 cells stably transfected with a 323-bp Htrp3 antisense construct (Htrp3AS), Northern blot analysis revealed that the expression of a 4-kb transcript was dramatically suppressed in comparison to that observed in cells stably transfected with a short Htrp3 sense construct (Htrp3S). Activity of SOCs, monitored as Ba(2+) influx following Ca(2+) store depletion with thapsigargin, was reduced by 32% in Htrp3AS cells in comparison with Htrp3S cells. Transient transfection of a 369-bp Htrp1 antisense construct in cells stably expressing Htrp3AS induced a higher level of inhibition (55%) of store-operated Ca(2+) entry. These data suggest that Htrp1 and Htrp3 may be functional subunits of SOCs.

Animals↗

High-calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension.

Because the effects of calcium supplementation on arterial tone in nitric oxide-deficient hypertension are unknown, we investigated the influence of elevating dietary calcium from 1.1 to 3.0% in Wistar rats treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg. kg(-1). day(-1)) for 8 wk. A high-calcium diet attenuated the development of hypertension induced by L-NAME and abrogated the associated impairments of endothelium-independent mesenteric arterial relaxations to nitroprusside, isoproterenol, and cromakalim. Endothelium-dependent relaxations to acetylcholine during nitric oxide synthase inhibition in vitro were decreased in L-NAME rats and improved by calcium supplementation. The inhibition of cyclooxygenase by diclofenac augmented the responses to acetylcholine in L-NAME rats but not in calcium + L-NAME rats. When hyperpolarization of smooth muscle was prevented by KCl precontraction, the responses to acetylcholine during combined nitric oxide synthase and cyclooxygenase inhibition were similar in all groups. Furthermore, superoxide dismutase enhanced the acetylcholine-induced relaxations in L-NAME rats but not in calcium + L-NAME rats. In conclusion, calcium supplementation reduced blood pressure during chronic nitric oxide synthase inhibition and abrogated the associated impairments in endothelium-dependent and -independent arterial relaxation. The augmented vasorelaxation after increased calcium intake in L-NAME hypertension may be explained by enhanced hyperpolarization and increased sensitivity to nitric oxide in arterial smooth muscle and decreased vascular production of superoxide and vasoconstrictor prostanoids.

Adrenergic beta-Agonists↗

Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney.

We examined in this study the expression of the potential-sensitive organic cation transporter OCT3 in the kidney. A functionally active OCT3 was cloned from a mouse kidney cDNA library. The cloned transporter was found to be capable of mediating potential-dependent transport of a variety of organic cations including tetraethylammonium. This function was confirmed in two different heterologous expression systems involving mammalian cells and Xenopus laevis oocytes. We have also isolated the mouse OCT3 gene and deduced its structure and organization. The OCT3 gene consists of 11 exons and 10 introns. In situ hybridization studies in the mouse kidney have shown that OCT3 mRNA is expressed primarily in the cortex. The expression is evident in the proximal and distal convoluted tubules. The expression of OCT3 in human kidney was confirmed by RT-PCR. We have also cloned OCT3 from human placenta and human kidney. Human OCT3 exhibits 86% identity with mouse OCT3 in amino acid sequence. Human OCT3 was found to transport tetraethylammonium and a variety of other organic cations. The transport process was electrogenic. We conclude that OCT3 is expressed in mammalian kidney and that it plays an important role in the renal clearance of cationic drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Atorvastatin coadministration may increase digoxin concentrations by inhibition of intestinal P-glycoprotein-mediated secretion.

The effect of atovarstatin on digoxin pharmacokinetics was assessed in 24 healthy volunteers in two studies. Subjects received 0.25 mg digoxin daily for 20 days, administered alone for the first 10 days and concomitantly with 10 mg or 80 mg atorvastatin for the last 10 days. Mean steady-state plasma digoxin concentrations were unchanged by administration of 10 mg atorvastatin. Mean steady-state plasma digoxin concentrations following administration of digoxin with 80 mg atorvastatin were slightly higher than concentrations following administration of digoxin alone, resulting in 20% and 15% higher Cmax and AUC(0-24) values, respectively. Since tmax and renal clearance were not significantly affected, the results are consistent with an increase in the extent of digoxin absorption in the presence of atorvastatin. Digoxin is known to undergo intestinal secretion mediated by P-glycoprotein. Since atorvastatin is a CYP3A4 substrate and many CYP3A4 substrates are also substrates for P-glycoprotein transport, the influence of atorvastatin and its metabolites on P-glycoprotein-mediated digoxin transport in monolayers of the human colon carcinoma (Caco-2) cell line was investigated. In this model system, atorvastatin exhibited efflux or secretion kinetics with a K(m) of 110 microM. Atorvastatin (100 microM) inhibited digoxin secretion (transport from the basolateral to apical aspect of the monolayer) by 58%, equivalent to the extent of inhibition observed with verapamil, a known inhibitor of P-glycoprotein transport. Thus, the increase in steady-state digoxin concentrations produced by 80 mg atorvastatin coadministration may result from inhibition of digoxin secretion into the intestinal lumen.

ATP Binding Cassette Transporter, Subfamily B, Mem↗