Biomedical subjects

L Xing

Publications and source records attributed to L Xing.

At least 73 records · Page 4Linked to original sources

PubMed1999

Physical characteristics of a miniature multileaf collimator.

A preliminary study of the physical characteristics of a miniature multileaf collimator (mMLC) used with 4 MV x rays is reported. The mMLC attached to the accessory mount of a class C or D Varian linear accelerator (Varian Oncology Systems, Palo Alto, CA) with a source to aperture distance of 65 cm. The field penumbra using the small leaves was found to be consistent with the anticipated field penumbra using photon jaws at the same source to aperture distance as the mMLC. The percentage depth dose values of square fields were found to be consistent with the fields collimated with the upper and lower jaws. Output factors for the very small fields were found to vary rapidly. Circular fields could be produced with depth dose characteristics similar to those produced using conical tertiary collimators, commonly used for radiosurgery, but with a broader penumbra.

Dose-Response Relationship, Radiation↗

PubMed1999

Theoretical considerations of monitor unit calculations for intensity modulated beam treatment planning.

A treatment planning system to compute intensity modulated radiotherapy (IMRT) treatments using inverse planning was investigated. The system was designed to optimize the intensity patterns required to treat a specified target volume with specified normal structure constraints. A beam model that uses the convolution of pencil beams was used to compute the dose distributions. A multileaf collimator leaf-setting sequence intended to produce the intensity pattern was computed along with the monitor units required to deliver each of a number of fixed-gantry modulated fields. Computer calculations are commonly verified using an independent manual procedure. It is difficult to calculate treatment delivery monitor units for this variant of IMRT using manual methods. Since manual calculations are not feasible, it is important both to understand and to verify the calculation of treatment monitor units by the planning system algorithm. A formal analysis was made of the dose calculation model and the monitor unit calculation embedded in the algorithm. Experimental verification of the dose delivered by plans computed with the methodology demonstrated an agreement of better than 4% between the dose model and measurements.

Algorithms↗

PubMed1999

Estimation theory and model parameter selection for therapeutic treatment plan optimization.

Treatment optimization is usually formulated as an inverse problem, which starts with a prescribed dose distribution and obtains an optimized solution under the guidance of an objective function. The solution is a compromise between the conflicting requirements of the target and sensitive structures. In this paper, the treatment plan optimization is formulated as an estimation problem of a discrete and possibly nonconvex system. The concept of preference function is introduced. Instead of prescribing a dose to a structure (or a set of voxels), the approach prioritizes the doses with different preference levels and reduces the problem into selecting a solution with a suitable estimator. The preference function provides a foundation for statistical analysis of the system and allows us to apply various techniques developed in statistical analysis to plan optimization. It is shown that an optimization based on a quadratic objective function is a special case of the formalism. A general two-step method for using a computer to determine the values of the model parameters is proposed. The approach provides an efficient way to include prior knowledge into the optimization process. The method is illustrated using a simplified two-pixel system as well as two clinical cases. The generality of the approach, coupled with promising demonstrations, indicates that the method has broad implications for radiotherapy treatment plan optimization.

Algorithms↗

PubMed1999

Matching photon and electron fields with dynamic intensity modulation.

A technique was developed to reduce the size and magnitude of the hot and cold spots in the abutting regions of photon and electron fields. The photon and electron fields were set up such that the photon field extended approximately 2 cm into the electron field in the abutting region. The region of the photon beam that overlapped the electron field was modulated using a multileaf collimator, effectively broadening the photon penumbra to make it complimentary to the electron penumbra. The computer calculations were verified using film measurements for abutting a 6 MV photon beam with a 9 MeV electron beam. A uniform dose was achieved at a prespecified depth of 2 cm, and dose uniformity was improved at the specified depth and beyond compared with unmodulated photon beams. A slight increase in dose inhomogeneity was seen at shallower depths. The overall areas of the hot and cold spots were significantly reduced. The technique also reduced the sensitivity of dose homogeneity to setup errors such that the magnitudes of the hot and cold spots were about half of those produced with unmodulated photon beam when an overlap or gap of 4 mm was introduced. The technique was applied to the treatment of a head and neck cancer and a lymphoma involving the right pleura with markedly reduced dose inhomogeneity in the abutting regions.

Computer Simulation↗

PubMed1999

Recent advances in bone biology provide insight into the pathogenesis of bone diseases.

Bone is modeled during embryonic development by endochondral and membranous ossification and is continuously remodeled thereafter under the influence of local and systemic factors to provide structural support and assist in calcium homeostasis. Recent studies of knockout and transgenic mice have increased understanding of the regulation of bone modeling during development and of remodeling of mature bone and have shed new light on the pathogenesis of a number of bone disorders. For example, fibroblast growth factor receptor-3, parathyroid hormone-related protein, and tartrate-resistant acid phosphatase affect the function of chondrocytes during endochondral ossification (the latter two by regulating their life spans and thus growth plate thickness and bone length). Some ubiquitously expressed genes seem unexpectedly to have unique functions that are largely confined to bone cells: M-CSF, C-Fos, PU.1, and NF-kappaB are required for osteoclast formation, whereas c-Src and Mitf (microphthalmia transcription factor) are required for osteoclast activity after the cells have formed. Knockout of these genes results in osteopetrosis, a disorder characterized by persistence in marrow cavities of unresorbed osteocartilaginous matrix and, as in some affected humans, by increased mortality. Some proteins seem to act as negative regulators of bone cell function, for example osteoprotegerin (a soluble TNF receptor) in osteoclasts; osteocalcin, bone sialoprotein, and 5-lipoxygenase in osteoblasts. Regulation of osteoclast life span may be an important mechanism by which estrogen and bisphosphonates prevent bone loss in conditions characterized by increased bone resorption, such as postmenopausal osteoporosis. The unique requirement of bone cells for certain gene products raises the possibility that these cells may have specific responses to inhibitory or stimulatory agents, and that signaling molecules in these response pathways could be specific targets for novel therapies to treat or prevent common bone diseases.

Animals↗

PubMed1999

[Cloning of glycoprotein B gene from strain Rispens of Marek's disease virus and construction of recombinant fowlpox virus].

Purified DNAs from Chicken Embryo Fibroblast (CEF) cultures infected with MDV strain Rispens were used as templates. Specific fragment with the size of about 2.9 kb was successfully amplified through Polymerase Chain Reaction(PCR) and identified to be gB gene of MDV by dot blot hybridization with a digoxigenin-labelled MDV gB specific oligonucleotide probe. The gB gene from strain Rispens was cloned into pUC19 and FPV insertion vector pFG1175-1 to construct plasmid pMGB and pFGBR1775-1 respectively. DOSPER liposome-mediated transfection with insertion vector DNA pFGBR1175-1 was performed on CEF monolayers infected with FPV 3-4 h earlier. Recombinant FPV was clone purified. Immunofluorescence Assay(IFA) showed that MDV gB gene had been expressed in FPV.

Animals↗

PubMed1998

LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon gamma (IFNgamma) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin beta receptor (LTbetaR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTbetaR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTbetaR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8(+) TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNgamma. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.

Apoptosis↗

PubMed1998

A test of the background selection hypothesis based on nucleotide data from Drosophila ananassae.

We estimated DNA sequence variation within and between four populations of Drosophila ananassae at Om(1D) and vermilion (v) by using single-strand conformation polymorphism analysis and direct DNA sequencing. Om(1D) is located on the X chromosome in a region with a normal recombination rate; v is in a region of low recombination. In each population, levels of nucleotide diversity at v are reduced 10- to 25-fold relative to those at Om(1D). Divergence between D. ananassae and its sibling species D. pallidosa, however, is comparable for both loci. This lack of correlation between levels of polymorphism and divergence led to the rejection of a constant-rate, neutral model. To distinguish among alternative models, we propose a test of the background selection hypothesis based on the observed pattern of differentiation between populations. Although the degree of differentiation (measured by FST) among all pairs of subpopulations is similar at Om(1D), we found substantial differences at v. The two northern populations from Burma and Nepal are very homogeneous, whereas comparisons between northern and southern populations (e.g., between Nepal and middle India) produced large FST values. A coalescent-based simulation of the background selection model (in a geographically structured species with a finite number of demes) showed that the observed homogeneity among the northern populations is inconsistent with the background selection hypothesis. Instead, it may have been caused by a recent hitchhiking event that was limited to the northern species range.

Animals↗

PubMed1998

An optimized leaf-setting algorithm for beam intensity modulation using dynamic multileaf collimators.

A leaf-setting algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimators (DMLCs). The algorithm starts with the algebraic expression for the area under the beam profile. It is shown that the coefficients in this expression can be transformed into the specifications for the leaf-setting sequence. It is proven that the algorithm optimizes beam delivery time and total monitor units for the DMLC leaf setting for intensity modulated radiotherapy (IMRT). The algorithm is demonstrated to be applicable to both the 'step-and-shoot' and 'dynamic' type of beam delivery. The graphical interpretation and numerical implementation scheme of the algorithm is illustrated using a simplified example.

Algorithms↗

PubMed1998

Fast iterative algorithms for three-dimensional inverse treatment planning.

Three types of iterative algorithms, algebraic inverse treatment planning (AITP), simultaneous iterative inverse treatment planning (SIITP), and iterative least-square inverse treatment planning (ILSITP), differentiated according to their updating sequences, were generalized to three dimension with true beam geometry and dose model. A rapid ray-tracing approach was developed to optimize the primary beam components. Instead of recalculating the dose matrix at each iteration, the dose distribution was generated by scaling up or down the dose matrix elements of the previous iteration. This significantly increased the calculation speed. The iterative algorithms started with an initial intensity profile for each beam, specified by a two-dimensional pixel beam map of M elements. The calculation volume was divided into N voxels, and the calculation was done by repeatedly comparing the calculated and desired doses and adjusting the values of the beam map elements to minimize an objective function. In AITP, the iteration is performed voxel by voxel. For each voxel, the dose discrepancy was evaluated and the contributing pencil beams were updated. In ILSITP and SIITP, the iteration proceeded pencil beam by pencil beam instead of voxel by voxel. In all cases, the iteration procedure was repeated until the best possible dose distribution was achieved. The algorithms were applied to two examples and the results showed that the iterative techniques were able to produce superior isodose distributions.

Algorithms↗

PubMed1998

A three-dimensional algorithm for optimizing beam weights and wedge filters.

An essential step towards optimizing and automating radiation therapy treatment planning is to develop an effective algorithm to find the optimal beam weights and wedge filters for a given set of beam directions and modalities. This problem is solved by introducing a variable transformation based on the universal and omni wedge principles. Instead of directly optimizing an objective function with respect to wedge angles and orientations, each field is first decomposed into a superposition of an open field and two orthogonal wedged fields. This transforms the problem of finding J beam weights, wedge angles, and orientations to that of optimizing a system with 3J beam weights (J open beams and 2J nominal wedged beams), where J is the total number of incident beam directions. An iterative algorithm based on a method originally developed for image reconstruction is used to find the 3J beam weights. The technique is applied to a few clinical cases. Treatment plans are improved compared to those obtained through the conventional manual trial and error planning process. In addition, planning time and effort are greatly reduced.

Algorithms↗

PubMed1998

Mesolimbic expression of neurotensin and neurotensin receptor during stress-induced gastric mucosal injury.

Neurotensin is a neurotransmitter present in the brain and gastrointestinal tract. Intracerebroventricular injection of neurotensin protects rats from gastric mucosal injury caused by cold water restraint (CWR). Direct injection of neurotensin into the nucleus accumbens (NACB), part of the mesolimbic dopamine system, reduces gastric mucosal injury, suggesting that neurotensin confers protection on the mucosa through interaction with the mesolimbic system. The hypothesis is that the concentration of neurotensin in the mesolimbic system decreases during CWR, affecting the expression of neurotensin and the neurotensin receptor. After 1 h of CWR, neurotensin concentration significantly decreased 41% in the NACB and returned toward control concentrations after 2 h of CWR. The concentration of neurotensin mRNA significantly decreased 46% after 1 h CWR and returned toward control after 2 h. In contrast, neurotensin binding sites in the NACB increased from 159 to 228 fmol/mg protein after 1 h of CWR and increased significantly to 280 fmol/mg protein after 2 h CWR, whereas the level of neurotensin receptor mRNA significantly decreased 51 and 50% at 1 and 2 h, respectively. These studies show that neurotensin concentration within the mesolimbic system is transiently reduced by CWR stress and that the number of neurotensin binding sites increases, presumably in response to the decrease in neurotensin.

Animals↗

PubMed1997

Requirement for NF-kappaB in osteoclast and B-cell development.

NF-kappaB is a family of related, dimeric transcription factors that are readily activated in cells by signals associated with stress or pathogens. These factors are critical to host defense, as demonstrated previously with mice deficient in individual subunits of NF-kappaB. We have generated mice deficient in both the p50 and p52 subunits of NF-kappaB to reveal critical functions that may be shared by these two highly homologous proteins. We now demonstrate that unlike the respective single knockout mice, the p50/p52 double knockout mice fail to generate mature osteoclasts and B cells, apparently because of defects that track with these lineages in adoptive transfer experiments. Furthermore, these mice present markedly impaired thymic and splenic architectures and impaired macrophage functions. The blocks in osteoclast and B-cell maturation were unexpected. Lack of mature osteoclasts caused severe osteopetrosis, a family of diseases characterized by impaired osteoclastic bone resorption. These findings now establish critical roles for NF-kappaB in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.

Animals↗

PubMed1997

Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice.

The Src tyrosine kinase has been implicated in a wide variety of signal transduction pathways, yet despite the nearly ubiquitous expression of c-src, src-/- mice show only one major phenotype-osteopetrosis caused by an intrinsic defect in osteoclasts, the cells responsible for resorbing bone. To explore further the role of Src both in osteoclasts and other cell types, we have generated transgenic mice that express the wild-type and mutated versions of the chicken c-src proto-oncogene from the promoter of tartrate resistant acid phosphatase (TRAP), a gene that is expressed highly in osteoclasts. We demonstrate here that expression of a wild-type transgene in only a limited number of tissues can fully rescue the src-/- phenotype. Surprisingly, expression of kinase-defective alleles of c-src also reduces osteopetrosis in src-/- animals and partially rescues a defect in cytoskeletal organization observed in src-/- osteoclasts. These results suggest that there are essential kinase-independent functions for Src in vivo. Biochemical examination of osteoclasts from these mice suggest that Src may function in part by recruiting or activating other tyrosine kinases.

Acid Phosphatase↗

PubMed1997

Antitumor activity of the novel human breast cancer growth inhibitor, mammary-derived growth inhibitor-related gene, MRG.

A novel human tumor growth inhibitor was identified by differential cDNA sequencing. The predicted amino acid sequence of this tumor-suppressing factor has a significant sequence homology to mouse mammary-derived growth inhibitor and thus was named mammary-derived growth inhibitor-related gene (MRG). MRG was found to be expressed in normal and benign human breast tissues but not in breast carcinomas. In situ hybridization analysis demonstrated a stage-specific MRG expression as follows. MRG was barely detectable in breast carcinomas, showed partial and weak expression in benign hyperplasia, but was expressed at a high level in normal breast epithelial cells. To determine if MRG can modulate in vivo growth of human breast cancers, we transfected a full-length MRG cDNA into MDA-MB-231 human breast cancer cells and studied the orthotopic growth of MRG transfectants versus control transfectants in the mammary fat pad of athymic nude mice. Overexpression of MRG in human breast cancer cells significantly suppressed cell proliferation in vitro and tumor growth in an orthotopic nude mouse model. These results suggest that MRG has tumor-suppressing activity, and the loss of MRG expression may be involved in the development and progression of breast cancer.

Amino Acid Sequence↗

PubMed1997

Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins.

A new member of the human cystatin superfamily, called cystatin E, has been found by expressed sequence tag (EST) sequencing in amniotic cell and fetal skin epithelial cell cDNA libraries. The sequence of a full-length amniotic cell cDNA clone contained an open reading frame encoding a putative 28-residue signal peptide and a mature protein of 121 amino acids, including four cysteine residues and motifs of importance for the inhibitory activity of Family 2 cystatins like cystatin C. Recombinant cystatin E was produced in a baculovirus expression system and isolated. An antiserum against the recombinant protein could be used for affinity purification of cystatin E from human urine, as confirmed by N-terminal sequencing. The mature recombinant protein processed by insect cells started at amino acid 4 (cystatin C numbering), and displayed reversible inhibition of papain and cathepsin B (Ki values of 0.39 and 32 nM, respectively), in competition with substrate. Cystatin E is thus a functional cysteine proteinase inhibitor despite relatively low amino acid sequence similarities with human cystatins (26-34% identity with sequences for the Family 2 cystatins C, D, S, SN, and SA; <30% with the Family 1 cystatins, A and B, and domains 2 and 3 of the Family 3 cystatin, kininogen). Unlike other human low Mr cystatins, cystatin E is a glycoprotein, carrying an N-linked carbohydrate chain at position 108. Northern blot analysis revealed that the cystatin E gene is expressed in most human tissues, with the highest mRNA amounts found in uterus and liver. A strikingly high incidence of cystatin E clones in cDNA libraries from fetal skin epithelium and amniotic membrane cells (>0.5% of clones sequenced) indicates a protective role of cystatin E during fetal development.

Amino Acid Sequence↗

PubMed1997

Optimization of relative weights and wedge angles in treatment planning.

An efficient technique to optimize beam weights and wedge angles in radiotherapy treatment planning has been developed. Based on the fact that a wedged field can be regarded as a superposition of an open field and a nominal wedged field, this approach reduces the problem of finding J beam weights and the corresponding wedge angles to optimizing a linear system with 2J unknowns (weights of J open beams and J nominal wedged beams), where J is the total number of incident beam directions. Two iterative algorithms similar to the iterative-least-square technique in image reconstruction are used to optimize the system. Application of the algorithms to two specific examples shows that this technique can reduce treatment planning time and effort, and promises to create a better solution for an arbitrarily complex treatment plan.

Algorithms↗

PubMed1997

QSAR models for binding of estrogenic compounds to estrogen receptor alpha and beta subtypes.

We have developed Quantitative Structure-Activity Relationship (QSAR) models based on Comparative Molecular Field Analysis (CoMFA) for 31 estrogenic chemicals whose relative binding affinity (RBA) is available for both ER-alpha and ER-beta. The models demonstrated a significant correlation (r2>0.95) between the CoMFA-calculated steric/electrostatic fields and corresponding RBA data and a good predictive capability (q2>0.6) based on cross-validation. The CoMFA models and contour plots obtained for ER-alpha and ER-beta suggest a close similarity between the receptors in terms of mode of binding and provide a rational basis for ligand selectivity.

Animals↗