Biomedical subjects

L Xing

Publications and source records attributed to L Xing.

At least 19 recordsLinked to original sources

PubMed2000

Induction and expression of beta-calcitonin gene-related peptide in rat T lymphocytes and its significance.

Our previous data have shown that rat lymphocytes can synthesize calcitonin gene-related peptide (CGRP), a neuropeptide. In this study the type, characteristics, and functional role of lymphocyte-derived CGRP were investigated. The results showed that treatment with Con A (4 microg/ml) and recombinant human IL-2 (rhIL-2; 750 U/ml) for 3-5 days induced CGRP synthesis and secretion by lymphocytes from both thymus and mesenteric lymph nodes in a time-dependent manner. Stimulation of these cells with Con A (1-8 microg/ml) or rhIL-2 (94-1500 U/ml) for 5 days induced a significant increase in CGRP secretion in a concentration-dependent manner. The maximal secretion of CGRP with Con A by thymocytes was elevated from 104+/-11 to 381 +/- 44 pg/10(8) cells, and that by mesenteric lymph node lymphocytes was elevated from 83+/-10 to 349+/-25 pg/10(8) cells, respectively. The maximal CGRP secretion with rhIL-2 by thymocytes was elevated from 116+/-3 to 607+/-23 pg/10(8), and that by mesenteric lymph node lymphocytes was elevated from 117+/-9 to 704+/- 37 pg/10(8) cells, respectively. The nucleotide sequencing study showed that lymphoid cells expressed beta-CGRP cDNA only. The levels of beta-CGRP mRNA in mitogen-stimulated lymphocytes of both sources were also increased. However, LPS had no such effect on either source of cells. hCGRP(8-37) (2.0 microM), a CGRP(1) receptor antagonist, enhanced Con A-induced proliferation and IL-2 release of thymocytes by 41.3 and 35.8% over those induced by Con A alone, respectively. The data suggest that T lymphocyte mitogens can induce the production of endogenous beta-CGRP from T lymphocytes, which may partially inhibit the proliferation and IL-2 release of rat T lymphocyte under immune challenges.

Animals↗

PubMed2000

Membrane proteins organize a symmetrical virus.

Alphaviruses are enveloped icosahedral viruses that mature by budding at the plasma membrane. According to a prevailing model maturation is driven by binding of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry of the membrane is thought to be imposed by the NC through one-to-one interactions between spike protomers and capsid proteins (CPs). This model is challenged here by a Semliki Forest virus capsid gene mutant. Its CPs cannot assemble into NCs, or its intermediate structures, due to defective CP-CP interactions. Nevertheless, it can use its horizontal spike-spike interactions on membrane surface and vertical spike-CP interactions to make a particle with correct geometry and protein stoichiometry. Thus, our results highlight the direct role of membrane proteins in organizing the icosahedral conformation of alphaviruses.

Electrophoresis, Polyacrylamide Gel↗

PubMed2000

Phytoreovirus T = 1 core plays critical roles in organizing the outer capsid of T = 13 quasi-equivalence.

The structures of the double-shelled rice dwarf virus and of its single-shell core have been determined by cryoelectron microscopy and image reconstruction. The core carries a prominent density located at each of the icosahedral faces of its T = 1 lattice. These protrusions are formed by outer shell trimers, tightly inserted at the threefold positions of the core. Such configuration of the core may guide the assembly of the outer shell, aided by lateral interactions between its subunits, into a T = 13 lattice. The organization of the phytoreovirus capsid elucidates for the first time a general model for assembling two unique T numbers of quasi-equivalence.

Animals↗

PubMed2000

Distinct cellular receptor interactions in poliovirus and rhinoviruses.

Receptor binding to human poliovirus type 1 (PV1/M) and the major group of human rhinoviruses (HRV) was studied comparatively to uncover the evolution of receptor recognition in picornaviruses. Surface plas- mon resonance showed receptor binding to PV1/M with faster association and dissociation rates than to HRV3 and HRV16, two serotypes that have similar binding kinetics. The faster rate for receptor association to PV1/M suggested a relatively more accessible binding site. Thermodynamics for receptor binding to the viruses and assays for receptor-mediated virus uncoating showed a more disruptive receptor interaction with PV1/M than with HRV3 or HRV16. Cryo-electron microscopy and image reconstruction of receptor-PV1/M complexes revealed receptor binding to the 'wall' of surface protrusions surrounding the 'canyon', a depressive surface in the capsid where the rhinovirus receptor binds. These data reveal more exposed receptor-binding sites in poliovirus than rhinoviruses, which are less protected from immune surveillance but more suited for receptor-mediated virus uncoating and entry at the cell surface.

Animals↗

PubMed2000

Gene discovery using the maize genome database ZmDB.

Zea mays DataBase (ZmDB) is a repository and analysis tool for sequence, expression and phenotype data of the major crop plant maize. The data accessible in ZmDB are mostly generated in a large collaborative project of maize gene discovery, sequencing and phenotypic analysis using a transposon tagging strategy and expressed sequence tag (EST) sequencing. ESTs constitute most of the current content. Database search tools, convenient links to external databases, and novel sequence analysis programs for spliced alignment are provided and together serve as an efficient protocol for gene discovery by sequence inspection. ZmDB can be accessed at http://zmdb. iastate.edu. ZmDB also provides web-based ordering of materials generated in the project, including EST and genomic DNA clones, seeds of mutant plants and microarrays of amplified EST and genomic DNA sequences.

Amino Acid Sequence↗

PubMed2000

Breast-conserving radiation therapy using combined electron and intensity-modulated radiotherapy technique.

BACKGROUND AND PURPOSE: To explore the feasibility of a multi-modality breast-conserving radiation therapy treatment technique to reduce high dose to the ipsilateral lung and the heart when compared with the conventional treatment technique using two tangential fields. MATERIALS AND METHODS: An electron beam with appropriate energy was combined with four intensity modulated photon beams. The direction of the electron beam was chosen to be tilted 10-20 degrees laterally from the anteroposterior direction. Two of the intensity-modulated photon beams had the same gantry angles as the conventional tangential fields, whereas the other two beams were rotated 15-25 degrees toward the anteroposterior directions from the first two photon beams. An iterative algorithm was developed which optimizes the weight of the electron beam as well as the fluence profiles of the photon beams for a given patient. Two breast cancer patients with early-stage breast tumors were planned with the new technique and the results were compared with those from 3D planning using tangential fields as well as 9-field intensity-modulated radiotherapy (IMRT) techniques. RESULTS: The combined electron and IMRT plans showed better dose conformity to the target with significantly reduced dose to the ipsilateral lung and, in the case of the left-breast patient, reduced dose to the heart, than the tangential field plans. In both the right-sided and left-sided breast plans, the dose to other normal structures was similar to that from conventional plans and was much smaller than that from the 9-field IMRT plans. The optimized electron beam provided between 70 to 80% of the prescribed dose at the depth of maximum dose of the electron beam. CONCLUSIONS: The combined electron and IMRT technique showed improvement over the conventional treatment technique using tangential fields with reduced dose to the ipsilateral lung and the heart. The customized beam directions of the four IMRT fields also kept the dose to other critical structures to a minimum.

Breast Neoplasms↗

PubMed2000

Dosimetric effects of patient displacement and collimator and gantry angle misalignment on intensity modulated radiation therapy.

PURPOSE AND OBJECTIVE: The primary goal of this study was to examine systematically the dosimetric effect of small patient movements and linear accelerator angular setting misalignments in the delivery of intensity modulated radiation therapy. We will also provide a method for estimating dosimetric errors for an arbitrary combination of these uncertainties. MATERIALS AND METHODS: Sites in two patients (lumbar-vertebra and nasopharynx) were studied. Optimized intensity modulated radiation therapy treatment plans were computed for each patient using a commercially available inverse planning system (CORVUS, NOMOS Corporation, Sewickley, PA). The plans used nine coplanar beams. For each patient the dose distributions and relevant dosimetric quantities were calculated, including the maximum, minimum, and average doses in targets and sensitive structures. The corresponding dose volumetric information was recalculated by purposely varying the collimator angle or gantry angle of an incident beam while keeping other beams unchanged. Similar calculations were carried out by varying the couch indices in either horizontal or vertical directions. The intensity maps of all the beams were kept the same as those in the optimized plan. The change of a dosimetric quantity, Q, for a combination of collimator and gantry angle misalignments and patient displacements was estimated using Delta=Sigma(DeltaQ/Deltax(i))Deltax(i). Here DeltaQ is the variation of Q due to Deltax(i), which is the change of the i-th variable (collimator angle, gantry angle, or couch indices), and DeltaQ/Deltax(i) is a quantity equivalent to the partial derivative of the dosimetric quantity Q with respect to x(i). RESULTS: While the change in dosimetric quantities was case dependent, it was found that the results were much more sensitive to small changes in the couch indices than to changes in the accelerator angular setting. For instance, in the first example in the paper, a 3-mm movement of the couch in the anterior-posterior direction can cause a 38% decrease in the minimum target dose or a 41% increase in the maximum cord dose, whereas a 5 degrees change in the θ(1)=20 degrees beam only gave rise to a 1.5% decrease in the target minimum or 5.1% in the cord maximum. The effect of systematic positioning uncertainties of the machine settings was more serious than random uncertainties, which tended to smear out the errors in dose distributions. CONCLUSIONS: The dose distribution of an intensity modulated radiation therapy (IMRT) plan changes with patient displacement and angular misalignment in a complex way. A method was proposed to estimate dosimetric errors for an arbitrary combination of uncertainties in these quantities. While it is important to eliminate the angular misalignment, it was found that the couch indices (or patient positioning) played a much more important role. Accurate patient set-up and patient immobilization is crucial in order to take advantage fully of the technological advances of IMRT. In practice, a sensitivity check should be useful to foresee potential IMRT treatment complications and a warning should be given if the sensitivity exceeds an empirical value. Quality assurance action levels for a given plan can be established out of the sensitivity calculation.

Humans↗

PubMed2000

Monitor unit calculation for an intensity modulated photon field by a simple scatter-summation algorithm.

An important issue in intensity modulated radiation therapy (IMRT) is the verification of the monitor unit (MU) calculation of the planning system using an independent procedure. Because of the intensity modulation and the dynamic nature of the delivery process, the problem becomes much more involved than that in conventional radiation therapy. In this work, a closed formula for MU calculation is derived. The approach is independent of the specific form of leaf sequence algorithms. It is straightforward to implement the procedure using a simple computer program. The approach is illustrated by a simplified example and is demonstrated by a few CORVUS (NOMOS Corporation, Sewickley, PA) treatment plans. The results indicate that it is robust and suitable for IMRT MU verification.

Algorithms↗

PubMed2000

Monte Carlo verification of IMRT dose distributions from a commercial treatment planning optimization system.

The purpose of this work was to use Monte Carlo simulations to verify the accuracy of the dose distributions from a commercial treatment planning optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented clinically to improve and verify the accuracy of radiotherapy dose calculations. Further modifications to the system were made to compute the dose in a patient for multiple fixed-gantry IMRT fields. The dose distributions in the experimental phantoms and in the patients were calculated and used to verify the optimized treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT dose distributions agreed with the measurements to within 2% of the maximum dose for all the beam energies and field sizes for both the homogeneous and heterogeneous phantoms. The dose distributions predicted by the Corvus system, which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte Carlo simulations and measurements to within 4% in a cylindrical water phantom with various hypothetical target shapes. Discrepancies of more than 5% (relative to the prescribed target dose) in the target region and over 20% in the critical structures were found in some IMRT patient calculations. The FSPB algorithm as implemented in the Corvus system is adequate for homogeneous phantoms (such as prostate) but may result in significant under or over-estimation of the dose in some cases involving heterogeneities such as the air-tissue, lung-tissue and tissue-bone interfaces.

Computer Simulation↗

PubMed2000

Computer verification of fluence map for intensity modulated radiation therapy.

In a treatment planning system for intensity modulated radiation therapy (IMRT), the time sequence of multileaf collimator (MLC) settings are derived from an optimal fluence map as a postoptimization process using a software module called a "leaf sequencer." The dosimetric accuracy of the dynamic delivery depends on the functionality of the module and it is important to verify independently the correctness of the leaf sequences for each field of a patient treatment. This verification is unique to the IMRT treatment and has been done using radiographic film, electronic portal imaging device (EPID) or electronic imaging system (BIS). The measurement tests both the leaf sequencer and the dynamic multileaf collimator (MLC) delivery system, providing a reliable assurance of clinical IMRT treatment. However, this process is labor intensive and time consuming. In this paper, we propose to separate quality assurance (QA) of the leaf sequencer from the dynamic MLC delivery system. We describe a simple computer algorithm for the verification of the leaf sequences. The software reads in the leaf sequences and simulates the motion of the MLC leaves. The generated fluence map is then compared quantitatively with the reference map from the treatment planning system. A set of pre-defined QA indices is introduced to measure the "closeness" between the computed and the reference maps. The approach has been used to validate the CORVUS (NOMOS Co., Sewickley, PA) treatment plans. The results indicate that the proposed approach is robust and suitable to support the complex IMRT QA process.

Algorithms↗

PubMed2000

Beam orientation optimization in intensity-modulated radiation treatment planning.

Beam direction optimization is an important problem in radiation therapy. In intensity modulated radiation therapy (IMRT), the difficulty for computer optimization of the beam directions arises from the fact that they are coupled with the intensity profiles of the incident beams. In order to obtain the optimal incident beam directions using iterative or stochastic methods, the beam profiles ought to be optimized after every change of beam configuration. In this paper we report an effective algorithm to optimize gantry angles for IMRT. In our calculation the gantry angles and the beam profiles (beamlet weights) were treated as two separate groups of variables. The gantry angles were sampled according to a simulated annealing algorithm. For each sampled beam configuration, beam profile calculation was done using a fast filtered backprojection (FBP) method. Simulated annealing was also used for beam profile optimization to examine the performance of the FBP for beam orientation optimization. Relative importance factors were incorporated into the objective function to control the relative importance of the target and the sensitive structures. Minimization of the objective function resulted in the best possible beam orientations and beam profiles judged by the given objective function. The algorithm was applied to several model problems and the results showed that the approach has potential for IMRT applications.

Algorithms↗

PubMed2000

Inverse planning incorporating organ motion.

Accurate targeting is important in intensity-modulated radiation therapy (IMRT). The positional uncertainties of structures with respect to the external beams arise in part from random organ motion and patient setup errors. While it is important to improve immobilization and reduce the influence of organ motion, the residual effects should be included in the IMRT plan design. Current inverse planning algorithms follow the conventional approach and include uncertainties by assuming population-based margins to the target and sensitive structures. Margin around a structure represents a "hard boundary" and the fact that a structure has a spatial probability distribution has been completely ignored. With increasing understanding of spatial uncertainties of structures and the technical capability of fine-tuning the dose distribution on an individual beamlet level in IMRT, it seems timely and important to fully utilize the information in the planning process. This will reduce the "effective" margins of the structures and facilitate dose escalation. Instead of specifying a "hard margin," we describe an inverse planning algorithm which takes into consideration positional uncertainty in terms of spatial probability distribution. The algorithm was demonstrated by assuming that the random organ motion can be represented by a three-dimensional Gaussian distribution function. Other probability distributions can be dealt with similarly. In particular, the commonly used "hard margin" is a special case of the current approach with a uniform probability distribution within a specified range. The algorithm was applied to plan treatment for a prostate case and a pancreatic case. The results were compared with those obtained by adding a margin to the clinical target volume. Better sparing of the sensitive structures were obtained in both cases using the proposed method for approximately the same target coverage.

Algorithms↗

PubMed2000

c-Src signaling induced by the adapters Sin and Cas is mediated by Rap1 GTPase.

Oncogenic Src proteins have been extensively studied to gain insight into the signaling mechanisms of Src. To better understand signaling through wild-type Src, we used an approach that involves activation of Src signaling through the binding of physiologic ligands to the Src SH3 domain. To this end, we used full-length and truncated versions of the multiadapter molecules Cas and Sin to activate c-Src, and we examined the intracellular pathways that mediate Src signaling under these conditions. We show that although all proteins bind to and are phosphorylated by c-Src, quantitative differences exist in the ability of the different ligands to activate c-Src signaling. In addition, we show that Sin- and Cas-induced Src signaling, as assayed by transcriptional activation, is exclusively mediated through a pathway that involves the adapter Crk and the GTP-binding protein Rap1. These data are in contrast to previous observations showing Ras to mediate signaling downstream of transforming Src alleles. In our system, we found that signaling through the oncogenic SrcY527 mutant is indeed mediated by Ras. In addition, we found that Rap1 also mediates oncogenic Src signaling. Our results show for the first time that Rap1 mediates c-Src kinase signaling and reveal mechanistic differences in the signaling properties of wild-type and transforming Src proteins.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes.

The three-dimensional structure of a self-assembled, recombinant hepatitis E virus particle has been solved to 22-A resolution by cryo-electron microscopy and three-dimensional image reconstruction. The single subunit of 50 kDa is derived from a truncated version of the open reading frame-2 gene of the virus expressed in a baculovirus system. This is the first structure of a T = 1 particle with protruding dimers at the icosahedral two-fold axes solved by cryo-electron microscopy. The protein shell of these hollow particles extends from a radius of 50 A outward to a radius of 135 A. In the reconstruction, the capsid is dominated by dimers that define the 30 morphological units. The outer domain of the homodimer forms a protrusion, which corresponds to the spike-like density seen in the cryo-electron micrograph. This particle retains native virus epitopes, suggesting its potential value as a vaccine.

Capsid↗

PubMed1999

Synchronizing dynamic multileaf collimators for producing two-dimensional intensity-modulated fields with minimum beam delivery time.

PURPOSE: Leaf motion synchronization of dynamic multileaf collimators (DMLC) for intensity-modulated radiotherapy (IMRT) is important in improving dose distribution and reducing "tongue-and-groove" effects for a prescribed intensity profile. Leaf synchronization could also be used in transforming a one-dimensional leaf-setting algorithm into a two-dimensional leaf-setting algorithm. In this work, we aim to develop a generalized leaf synchronization method for delivering IMRT with the minimized beam delivery time and the optimized subfield variations for a leaf-setting sequence. METHODS AND MATERIALS: With the leaf synchronization procedure, all active MLC leaf pairs start and finish off a leaf sequence simultaneously. In this work, the MLC leaf pairs were synchronized under the condition that the resulting leaf sequence produces the desired intensity profile with the minimum beam delivery time. The parameter of the leaf synchronization function was determined through the least-square minimization of the area variations of all subfields within a leaf sequence. The leaf synchronization and optimization procedure were applied and analyzed for clinical relevant intensity profiles for treating the head-and-neck cancer patients using IMRT. RESULTS: The total monitor units and the optimized beam delivery time of generating a two-dimensional intensity profile was proven through this work to be the global minimum of all leaf-setting sequences including the unsynchronized leaf-setting sequences. The optimized parameter for subfield variations of the synchronized leaf trajectories was found to be dependent on individual intensity profiles. For all our studied cases, the unsynchronized leaf trajectories always have significantly larger subfield variations than the synchronized leaf trajectories. CONCLUSION: It is important and also feasible to synchronize and optimize dynamic MLC leaf motions while still keeping the total beam delivery time minimum for delivering arbitrary two-dimensional intensity-modulated fields.

Algorithms↗

PubMed1999

Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus.

A cDNA encoding the human guanylate binding protein-1 (hGBP-1) was expressed in HeLa cells using a constitutive expression vector. Stably transfected clones expressing hGBP-1 exhibited resistance to the cytopathic effect mediated by both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) and produced less viral progeny than control cells following infection with these viruses. To study the role hGBP-1 plays in the IFN-mediated antiviral effect, cells were stably transfected with a construct expressing antisense RNA for hGBP-1. VSV infection of IFN-alpha-treated antisense RNA-expressing cells produced an amount of virus comparable to that produced in the parental cell line, while EMCV infection of the IFN-alpha-treated transfected cells and VSV and EMCV infection of the IFN-gamma-treated transfected cells produced far more virus than was produced in the parental cell line. These results demonstrate that GBP-1 mediates an antiviral effect against VSV and EMCV and plays a role in the IFN-mediated antiviral response against these viruses.

DNA-Binding Proteins↗

PubMed1999

Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand.

Among members of the tumor necrosis factor receptor (TNFR) superfamily, 4-1BB, CD27, and glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) share a striking homology in the cytoplasmic domain. Here we report the identification of a new member, activation-inducible TNFR family member (AITR), which belongs to this subfamily, and its ligand. The receptor is expressed in lymph node and peripheral blood leukocytes, and its expression is up-regulated in human peripheral mononuclear cells mainly after stimulation with anti-CD3/CD28 monoclonal antibodies or phorbol 12-myristate 13-acetate/ionomycin. AITR associates with TRAF1 (TNF receptor-associated factor 1), TRAF2, and TRAF3, and induces nuclear factor (NF)-kappaB activation via TRAF2. The ligand for AITR (AITRL) was found to be an undescribed member of the TNF family, which is expressed in endothelial cells. Thus, AITR and AITRL seem to be important for interactions between activated T lymphocytes and endothelial cells.

Amino Acid Sequence↗

PubMed1999

Identification and characterization of immunoreactive calcitonin gene-related peptide from lymphocytes of the rat.

There is accumulating evidence that the immune system can produce neuropeptides. In the light of these facts, we obtained direct evidences to prove that T lymphocytes also synthesize and secrete calcitonin gene-related peptide (CGRP), a neuropeptide localized within primary sensory nerves. By using CGRP specific RIA, CGRP-like immunoreactivity (LI) was found in the extracts of rat lymphocytes from thymus and mesenteric lymph node. The intracellular concentration of lymphocyte-derived CGRP-LI of rat thymus and mesenteric lymph node was 745+/-39 and 447+/-33 fg/10(6) cells, respectively. CGRP-LI in lymphocytes was shown to co-elute with synthetic rat CGRP and sensory neuron-derived CGRP by reverse-phase HPLC. In addition, the CGRP-LI located in the T lymphocytes was also shown by immunocytochemical method examined by electron microscopy. The CGRP mRNA detected by RT-PCR was also present in these lymphocytes and was also identified to be the same one in sensory neurons. These data suggest that CGRP is synthesized and secreted in T lymphocytes of both thymus and lymph node in the rat, and this is identified to be the same one in neuronal tissue. Lymphocyte-derived CGRP may act in an autocrine/paracrine mode and play an important role in certain physiological and pathophysiological conditions.

Animals↗