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Biomedical subjects

Y Zhu

Publications and source records attributed to Y Zhu.

At least 289 records · Page 16Linked to original sources
PubMed2000

Late effects in survivors of infant leukemia.

Little is known about the incidence of and risk factor for late effects of infant leukemia. We evaluated 19 children with acute lymphoblastic leukemia and 15 with acute myeloid leukemia who were diagnosed at age 12 months or younger and have survived for more than 5 years after the diagnosis (median length of follow-up, 13 years; range, 5.7-29 years). Ten patients received chemotherapy alone (group A), 17 received chemotherapy and CNS-directed radiation therapy (CRT) (group B), and seven received chemotherapy, CRT and bone marrow transplantation (group C). The most frequently observed late sequelae included problems in growth (66% of survivors), learning (50%), hypothyroidism (15%), and pubertal development (12%). Cataract, cardiac and hearing abnormalities occurred in 6% of patients. Only eight patients (24%) survive without late effects. In comparison to patients in group A, patients in groups B and C had a higher incidence of having at least one late complication (P = 0.009), a greater decrease in height Z score at 5 years after diagnosis (P = 0.023), and a higher incidence of academic difficulties (P = 0.004). The estimated odds of academic difficulties increased by 18% (P = 0.032) for each month younger in age at the time of CRT. These results indicate that late sequelae are common in longterm survivors of infant leukemia and are often related to CRT and the patient's age at the time of CRT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Mutations conferring amino acid residue substitutions in the carboxy-terminal domain of RNA polymerase alpha can suppress clpX and clpP with respect to developmentally regulated transcription in Bacillus subtilis.

The Bacillus subtilis clpX and clpP genes are the sites of pleiotropic mutations that adversely affect growth on a variety of media and impair developmental processes such as sporulation and competence development. ClpX is necessary for the post-exponential induction of genes that require the sigmaH form of RNA polymerase for transcription. Both ClpX and ClpP are required for the activation of sigmaA-dependent transcription of the srf operon that encodes surfactin synthetase and the regulatory peptide ComS, required for the development of genetic competence. Transcription of srf is activated by the two-component regulatory system ComPA in response to the peptide pheromone, ComX, which mediates cell density-dependent control. A clpX mutant, although able to produce ComX, is unable to respond to the pheromone. A mutant allele of comP, encoding a product whose activity is independent of ComX, is not able to suppress clpX with respect to srf expression, suggesting that ClpXP acts at the level of ComA-dependent activation of srf transcription initiation. Suppressor mutations of clpX (cxs-1 and cxs-2) were isolated in screens for pseudorevertants exhibiting high levels of srf expression and sigmaH-dependent transcription respectively. One mutation, cxs-1, suppressed a clpP null mutation with respect to srf transcription, but did not overcome the block conferred by clpP on competence development and sporulation. Both cxs-1 and cxs-2 mutations map to the region of the rpoA gene encoding the RNA polymerase alpha C-terminal domain (alphaCTD). The reconstruction of the cxs-1 and cxs-2 alleles of rpoA confirmed that these mutations confer the suppressor phenotype. These findings provide further support for the hypothesis that ClpX and ClpP might be intimately associated with transcription initiation in B. subtilis.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2000

Interaction of ResD with regulatory regions of anaerobically induced genes in Bacillus subtilis.

The two-component regulatory proteins ResD and ResE are required for anaerobic nitrate respiration in Bacillus subtilis. ResD, when it undergoes ResE-dependent phosphorylation, is thought to activate transcriptionally anaerobically induced genes such as fnr, hmp and nasD. In this report, deletion analysis of the fnr, hmp and nasD promoter regions was carried out to identify cis-acting sequences required for ResDE-dependent transcription. The results suggest that the hmp and nasD promoters have multiple target sequences for ResDE-dependent regulation and that fnr has a single target site. Gel mobility shift assays and DNase I footprinting analyses were performed to determine whether ResD interacts directly with the regulatory regions of the three genes. Our results indicate that ResD specifically binds to sequences residing upstream of the hmp and nasD promoters and that phosphorylation of ResD significantly stimulates this binding. In contrast, a higher concentration of ResD is required for binding to the fnr promoter region and no stimulation of the binding by ResD phosphorylation was observed. Taken together, these results suggest that ResD activates transcription of fnr, hmp and nasD by interacting with DNA upstream of these promoters. Our results suggest that phosphorylation of ResD stimulates binding to multiple ResD binding sites, but is much less stimulatory if only a single binding site exists.

ATP-Binding Cassette Transporters↗
PubMed2000

Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas.

Tangier disease (TD) fibroblasts have defective cholesterol release in the presence of lipid-free apolipoproteins. We compared normolipidemic probands and patients with apolipoprotein A-I (apoA-I) deficiency, apoE deficiency, or TD in terms of the plasma capacity to induce the efflux of [3H]-cholesterol from normal and TD fibroblasts and to esterify this cell-derived cholesterol. Compared with normal fibroblasts, TD fibroblasts released a significantly smaller fraction of [3H]-cholesterol into normal, high-density lipoprotein (HDL)-deficient, and apoE-deficient plasmas. Supplementation of apoE-deficient plasma with exogenous apoE normalized the cholesterol efflux from normal cells but did not fully restore the reduced cholesterol efflux from TD fibroblasts. Compared with control plasma, HDL- and apoE-deficient plasmas had a significantly reduced activity to esterify cell-derived cholesterol. Cholesterol derived from TD fibroblasts was less available for esterification in either patient or normal plasmas than cholesterol derived from normal cells. The esterification defect of TD cell-derived cholesterol was more pronounced in patient plasmas than in control plasma. We conclude that (1) apoA-I and, to a lesser degree, apoE are important determinants of the cholesterol efflux and esterification capacity of plasma, (2) TD fibroblasts have a reduced capacity to release cholesterol into the plasma, and (3) TD cell-derived cholesterol is less available for esterification in plasma than cholesterol from normal fibroblasts. The absence of distinct apoA-I- or apoE-containing subclasses aggravates the defective efflux and esterification of cholesterol derived from TD cells.

Adult↗
PubMed2000

Do cerebral potentials to magnetic stimulation of paraspinal muscles reflect changes in palpable muscle spasm, low back pain, and activity scores?

OBJECTIVE: Previous studies have shown that cortical-evoked potentials on magnetic stimulation of muscles are influenced by muscle contraction, vibration, and muscle spasm. This study was carried out to determine whether these potentials correlate with palpatory muscle spasm, patient symptoms, and disability in patients with low back pain. METHODS: A prospective observational study was performed on 13 subjects with a history of low back pain visiting an orthopedic hospital-based clinic. Patients were screened for serious pathologic conditions by an orthopedic surgeon. The patients were then evaluated for the presence of muscle spasm by one of the investigators who was blinded to the results of the evoked potential studies. Patients were asked to complete a low back pain visual analogue scale (VAS) and a Roland-Morris Activity Scale (RMAS). Cortical-evoked potentials were recorded with a magnetic stimulator placed over the lumbar paraspinal muscles with the patient in the prone position. The palpatory examination, VAS, RMAS, and the cortical potentials were repeated after 2 weeks of therapy commonly used to reduce muscle spasm. RESULTS: The patients demonstrated a significant decrease in low back pain VAS and RMAS scores after treatment compared with before treatment. There was a reduction in the amount of palpatory muscle spasm in 11 of 13 cases. The cortical potentials before treatment were attenuated compared with previously reported controls and showed a significant increase before and after treatment in the amplitude of these potentials with multivariate analysis of variance. There was significant correlation between the changes in cortical potentials after treatment and the changes noted in paraspinal muscle spasm and VAS and RMAS scores. CONCLUSIONS: This study confirms the previous report that the amplitude of cerebral-evoked potentials on magnetic stimulation of paraspinal muscles is depressed in the presence of palpable muscle spasm. The close correlation among these potentials, paraspinal muscle spasm, and clinical symptoms suggests that the measurement of muscle activity may be more important in the assessment of low back pain than is commonly accepted.

Adult↗
PubMed2000

Linear programming based on neural networks for radiotherapy treatment planning.

In this paper, we propose a neural network model for linear programming that is designed to optimize radiotherapy treatment planning (RTP). This kind of neural network can be easily implemented by using a kind of 'neural' electronic system in order to obtain an optimization solution in real time. We first give an introduction to the RTP problem and construct a non-constraint objective function for the neural network model. We adopt a gradient algorithm to minimize the objective function and design the structure of the neural network for RTP. Compared to traditional linear programming methods, this neural network model can reduce the time needed for convergence, the size of problems (i.e., the number of variables to be searched) and the number of extra slack and surplus variables needed. We obtained a set of optimized beam weights that result in a better dose distribution as compared to that obtained using the simplex algorithm under the same initial condition. The example presented in this paper shows that this model is feasible in three-dimensional RTP.

Algorithms↗
PubMed2000

A neural network regression model for relative dose computation.

This paper describes a neural network (NN) regression model for relative dose computation. The input signal of the NN model includes depths and field sizes and the output is the relative dose, for example, percentage depth dose (%DD) or tissue-air ratio (TAR) in this paper. After a functional link has been created, the expressing ability of input patterns and the resolution of neural networks are enhanced. The trained neural network exhibits a good generalization and interpolation ability, and it can be easily extended to other relative dose regressions. We present two examples to verify the fitness of this model. The first calculates the percentage depth dose of a 14 MV x-ray beam for field sizes of 5 cm x 5 cm to 28 cm x 28 cm. The average error computed from the NN is less than 0.47% comparing with the original measured %DD. The second example calculates the TAR of a 4 MV x-ray beam for field sizes of 5 cm x 5 cm to 20 cm x 20 cm. In this example, the training data show that the average error computed from the NN is less than 0.48%, whereas that from the testing data is less than 0.37% after training. Such an NN model can be generalized to fit data for treatment planning with any linear accelerator and can also fit data stored as tissue-maximum ratio (TMR) and tissue-phantom ratio (TPR).

Linear Models↗
PubMed2000

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↗
PubMed2000

Preparation and characterization of mabs against different epitopes of CD226 (PTA1).

Recently the platelet and T-cell activation antigen 1 (PTA1) was assigned as CD226 at the 7th Conference and Workshop on Human Leukocyte Differentiation antigens (HLDA). PTA1 is mainly expressed on activated T cells, natural killer (NK) cells, platelets and stimulated endotheliocytes, and involved in the differentiation of cytotoxic T lymphocytes (CTL) and NK, as well as platelet activation and aggregation. We raised hybridomas secreting monoclonal antibodies (MAbs) to PTA1 by using the natural PTA1 as immunogen, which was purified from platelets via affinity chromatography. These MAbs, designated FMU1, FMU2, FMU3, FMU4, FMU5, FMU6 and FMU7, could recognize PTA1 cDNA transfected COS7 cells detected by flow cytometry (FCM), and also react with both natural PTA1 and PTA1/Ig fusion protein in indirect enzyme-linked immunoadsorbent assay (ELISA). The biosensor epitope mapping assay showed that the seven MAbs, together with previous PTA1-specific MAbs Leo A1 and New E1, could bind seven distinct epitopes of PTA1, respectively. The panel of MAbs might be new powerful tools to study the structure-function relationship of PTA1 molecule, and to search for the ligand of PTA1.

Animals↗
PubMed2000

The assembly of AP-3 adaptor complex-containing clathrin-coated vesicles on synthetic liposomes.

The heterotetrameric adaptor protein complex AP-3 has been shown to function in the sorting of proteins to the endosomal/lysosomal system. However, the mechanism of AP-3 recruitment onto membranes is poorly understood, and it is still uncertain whether AP-3 nucleates clathrin-coated vesicles. Using purified components, we show that AP-3 and clathrin are recruited onto protein-free liposomes and Golgi-enriched membranes by a process that requires ADP-ribosylation factor (ARF) and GTP but no other proteins or nucleotides. The efficiency of recruitment onto the two sources of membranes is comparable and independent of the composition of the liposomes. Clathrin binding occurred in a cooperative manner as a function of the membrane concentration of AP-3. Thin-section electron microscopy of liposomes and Golgi-enriched membranes that had been incubated with AP-3, clathrin, and ARF.GTP showed the presence of clathrin-coated buds and vesicles. These results establish that AP-3-containing clathrin-coated vesicles form in vitro and are consistent with AP-3-dependent protein transport being mediated by clathrin-coated vesicles.

ADP-Ribosylation Factor 1↗
PubMed2000

Interaction between monocytes and vascular smooth muscle cells enhances matrix metalloproteinase-1 production.

Matrix metalloproteinase-1 (MMP-1) plays an important role in atherosclerotic plaque rupture. The purpose of this study was to investigate the expression of MMP-1 by cell-to-cell interactions between monocytes and vascular smooth muscle cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cells) were cocultured. MMP-1 levels were measured by enzyme-linked immunosorbent assay. Collagenolytic activity was determined by fluorescent labeled-collagen digestion. Immunohistochemistry was performed to determine which types of cells produce MMP-1. Adding THP-1 cells to VSMCs markedly increased the MMP-1 levels and activity of the culture media. MMP-1 levels were maximal when the cellular ratio of THP-1 cells/VSMCs was 1.0. Immunohistochemistry revealed that both types of cells in the coculture produced MMP-1. Separated coculture experiments showed that both direct contact and a soluble factor(s) contributed to MMP-1 production. Neutralizing anti-interleukin (IL)-6 and tumor necrosis factor-alpha antibodies inhibited coculture conditioned medium-induced MMP-1 production by VSMCs and THP-1 cells. Protein kinase C inhibitors, tyrosine kinase inhibitors, and a mitogen-activated protein kinase inhibitor significantly inhibited MMP-1 production by cocultures. Direct cell-to-cell interaction between THP-1 cells and VSMCs enhanced MMP-1 synthesis in both types of cells. Increased local MMP-1 production and activity induced by monocyte-VSMC interaction play an important pathogenic role in atherosclerotic plaque rupture.

Cell Adhesion↗
PubMed2000

Selecting beam weight and wedge filter on the basis of dose gradient analysis.

This study proposes an algorithm for selecting beam weight, wedge angle, and wedge orientation for three-dimensional radiation therapy treatment planning. According to dose gradient analysis, the necessary and sufficient condition for achieving a homogeneous dose over the target volume is that the total vector sum of the dose gradients of all beams be zero everywhere in the target volume. This study presents equations for calculating the beam weight, wedge angle, and collimator angle (because the collimator angle determines wedge orientation when beam direction is known) for treatment plans using two angled beams or three coplanar or noncoplanar beams. It also provides suggestions for calculations of treatment plans using more than three beams, for which many feasible solutions will be available. When tested using two clinical cases, this algorithm achieved homogeneous dose distributions over target volumes. With this algorithm, repeated manual adjustments are reduced, and the quality and efficiency of treatment planning are improved.

Algorithms↗
PubMed2000

Adaptive portal CT reconstruction: a simulation study.

In radiotherapy, radiation treatment beams contain valuable information for patient setup verification. These beams may be used for portal CT reconstruction. However, direct use of the beam data for reconstruction may yield inadequate CT images simply because these beams cover only a part of the patient body. In this study, we use the treatment beams in addition to a set of regular CT projection beams to reconstruct a locally enhanced portal CT image. This approach is called adaptive portal CT reconstruction. A computer simulation demonstrated the advantages of the approach. The image reconstruction was carried out by the multilevel scheme algebraic reconstruction technique. Results indicated that the image quality of adaptive portal CT reconstruction is equivalent to that obtained from a full set of projections. This proposed technique should be not only valuable for three-dimensional radiotherapy verification, but also applicable to diagnostic CT imaging.

Computer Simulation↗
PubMed2000

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↗
PubMed2000

Optimizing beam weights and wedge filters with the concept of the super-omni wedge.

This study introduces a new concept, the super-omni wedge, and proposes an algorithm for optimizing beam weights, wedge angles, and wedge orientations on the basis of this new concept. The super-omni wedge is a generalization of the omni wedge. Instead of combining one open beam and two orthogonal wedged beams, it uses two orthogonal pairs of nominal wedged beams to generate a wedged dose distribution with an arbitrary wedge angle and an arbitrary wedge orientation. The orientations of a pair of nominal wedges are opposite each other. In this way, the effective wedge orientation can vary from 0 degrees to 360 degrees rather than being restricted to one quadrant. When the concept of the super-omni wedge is used, the optimization of beam weights, wedge angles, and wedge orientations for J beams is transformed into the optimization of beam weights for 4J beams. A quadratic dose-based objective function is defined, and the method of sequential quadratic programming is used to find the 4J beam weights that minimize it. After the weights of the nominal wedged beams have been determined, the beams can be delivered in one of four methods: Directly, by using the omni wedge technique, by using the universal wedge technique, and by using the virtual wedge technique. When tested with two clinical cases, the algorithm achieved homogeneous dose distributions in target volumes while meeting the constraints to the organs at risk. A prominent feature of the algorithm is that there is no need to manually preselect the orientations of nominal wedges.

Algorithms↗
PubMed2000

Maximum-likelihood approach to strain imaging using ultrasound

A maximum-likelihood (ML) strategy for strain estimation is presented as a framework for designing and evaluating bioelasticity imaging systems. Concepts from continuum mechanics, signal analysis, and acoustic scattering are combined to develop a mathematical model of the ultrasonic waveforms used to form strain images. The model includes three-dimensional (3-D) object motion described by affine transformations, Rayleigh scattering from random media, and 3-D system response functions. The likelihood function for these waveforms is derived to express the Fisher information matrix and variance bounds for displacement and strain estimation. The ML estimator is a generalized cross correlator for pre- and post-compression echo waveforms that is realized by waveform warping and filtering prior to cross correlation and peak detection. Experiments involving soft tissuelike media show the ML estimator approaches the Cramer-Rao error bound for small scaling deformations: at 5 MHz and 1.2% compression, the predicted lower bound for displacement errors is 4.4 microns and the measured standard deviation is 5.7 microns.

Journal Article↗
PubMed2000

Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist.

The cysteinyl leukotrienes (CysLTs) are potent biological mediators in the pathophysiology of inflammatory diseases, in particular of airway obstruction in asthma. Pharmacological studies have suggested the existence of at least two types of CysLT receptors, designated CysLT(1) and CysLT(2). The CysLT(1) receptor has been cloned recently. Here we report the molecular cloning, expression, localization, and functional characterization of a human G protein-coupled receptor that has the expected characteristics of a CysLT(2) receptor. This new receptor is selectively activated by nanomolar concentrations of CysLTs with a rank order potency of LTC(4) = LTD(4) >> LTE(4). The leukotriene analog BAY u9773, reported to be a dual CysLT(1)/CysLT(2) antagonist, was found to be an antagonist at CysLT(1) sites but acted as a partial agonist at this new receptor. The structurally different CysLT(1) receptor-selective antagonists zafirlukast, montelukast, and MK-571 did not inhibit the agonist-mediated calcium mobilization of CysLT(2) receptors at physiological concentrations. Localization studies indicate highest expression of CysLT(2) receptors in adrenal glands, heart, and placenta; moderate levels in spleen, peripheral blood leukocytes, and lymph nodes; and low levels in the central nervous system and pituitary. The human CysLT(2) receptor gene is located on chromosome 13q14.12-21.1. The new receptor exhibits all characteristics of the thus far poorly defined CysLT(2) receptor. Moreover, we have identified BAY u9773 as a CysLT(2) selective agonist, which could prove to be of immediate use in understanding the functional roles of the CysLT(2) receptor.

Amino Acid Sequence↗