Showing papers by "Kyoto University published in 2005"
27 Oct 2005
TL;DR: A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.
5,479 citations
TL;DR: Improvement in accuracy was generally observed for most methods, but remarkably large for the new options of MAFFT proposed here, which showed higher accuracy than currently available methods including TCoffee version 2 and CLUSTAL W in benchmark tests consisting of alignments of >50 sequences.
Abstract: The accuracy of multiple sequence alignment program MAFFT has been improved. The new version (5.3) of MAFFT offers new iterative refinement options, H-INS-i, F-INS-i and G-INS-i, in which pairwise alignment information are incorporated into objective function. These new options of MAFFT showed higher accuracy than currently available methods including TCoffee version 2 and CLUSTAL W in benchmark tests consisting of alignments of >50 sequences. Like the previously available options, the new options of MAFFT can handle hundreds of sequences on a standard desktop computer. We also examined the effect of the number of homologues included in an alignment. For a multiple alignment consisting of ∼8 sequences with low similarity, the accuracy was improved (2–10 percentage points) when the sequences were aligned together with dozens of their close homologues (E-value < 10−5–10−20) collected from a database. Such improvement was generally observed for most methods, but remarkably large for the new options of MAFFT proposed here. Thus, we made a Ruby script, mafftE.rb, which aligns the input sequences together with their close homologues collected from SwissProt using NCBI-BLAST.
4,528 citations
TL;DR: Naturally arising CD25+CD4+ regulatory T cells actively maintain immunological self-tolerance, and are a good target for designing ways to induce or abrogate immunological tolerance to self and non-self antigens.
Abstract: Naturally arising CD25+CD4+ regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish transplantation tolerance. They are therefore a good target for designing ways to induce or abrogate immunological tolerance to self and non-self antigens.
2,683 citations
TL;DR: In this paper, the results of the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC) were examined with an emphasis on implications for the formation of a new state of dense matter.
2,572 citations
TL;DR: IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection and blocked interferon induction by virus infection.
Abstract: Type I interferons are central mediators for antiviral responses. Using high-throughput functional screening of interferon inducers, we have identified here a molecule we call interferon-beta promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-kappaB transcription factors. TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction. IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection. 'Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I- and Mda5-mediated antiviral immune responses.
2,440 citations
TL;DR: The results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.
Abstract: The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type I IFN. RIG-I contains a domain that belongs to a DExD/H-box helicase family and exhibits an N-terminal caspase recruitment domain (CARD) homology. There are three genes encoding RIG-I-related proteins in human and mouse genomes. Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I. Both proteins sense viral RNA with a helicase domain and transmit a signal downstream by CARD; thus, these proteins share overlapping functions. Another protein, LGP2, lacks the CARD homology and functions as a negative regulator by interfering with the recognition of viral RNA by RIG-I and MDA5. The nonstructural protein 3/4A protein of hepatitis C virus blocks the signaling by RIG-I and MDA5; however, the V protein of the Sendai virus selectively abrogates the MDA5 function. These results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.
1,632 citations
TL;DR: Findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation and broaden the knowledge of the functions Wnt proteins have at various stages of skeletogenesis.
1,446 citations
TL;DR: It is shown that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs and promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin.
Abstract: Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells. Free fatty acids (FFAs) provide an important energy source and also act as signaling molecules in various cellular processes, including the secretion of gut incretin peptides. Here we show that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs. Furthermore, we show that the stimulation of GPR120 by FFAs promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin. Because GLP-1 is the most potent insulinotropic incretin, our results indicate that GPR120-mediated GLP-1 secretion induced by dietary FFAs is important in the treatment of diabetes.
1,385 citations
TL;DR: In this article, the authors demonstrate the importance of the formation of a photonic double-heterostructure, which has resulted in the realization of extremely high-quality factor photonic nanocavities with 600,000, more than one order of magnitude higher than any previous reports.
Abstract: High-quality factor (Q) photonic nanocavities that strongly confine photons in volumes of optical-wavelength dimension are attracting much attention in various fields, including photonics1,2,3,4,5, telecommunications6,7, quantum information8 and cavity quantum electrodynamics9,10, because a strong light–matter interaction is obtained. An important design rule has been proposed11 in an attempt to realize high-Q nanocavities in two-dimensional photonic-crystal slabs. The form of the cavity electric-field distribution should slowly vary, most ideally as described by a gaussian function, in order to suppress out-of-slab photon leakage. However, the exact cavity structure that minimizes photon leakage has not yet been established. Here, we demonstrate the importance of the formation of a photonic double-heterostructure, which has resulted in the realization of nanocavities with extremely high-Q factors of 600,000, more than one order of magnitude higher than any previous reports11,12,13,14. We have also shown theoretically that Q-factors greater than 20,000,000 may be obtained when optimizing the structure.
1,357 citations
TL;DR: FLOWERING LOCUS T (FT) is a conserved promoter of flowering that acts downstream of various regulatory pathways, including one that mediates photoperiodic induction through CONSTANS (CO), and is expressed in the vasculature of cotyledons and leaves.
Abstract: FLOWERING LOCUS T (FT) is a conserved promoter of flowering that acts downstream of various regulatory pathways, including one that mediates photoperiodic induction through CONSTANS (CO), and is expressed in the vasculature of cotyledons and leaves. A bZIP transcription factor, FD, preferentially expressed in the shoot apex is required for FT to promote flowering. FD and FT are interdependent partners through protein interaction and act at the shoot apex to promote floral transition and to initiate floral development through transcriptional activation of a floral meristem identity gene, APETALA1 (AP1). FT may represent a long-distance signal in flowering.
1,344 citations
TL;DR: High levels of selective sorption of acetylene molecules as compared to a very similar molecule, carbon dioxide, onto the functionalized surface of a MOM are reported.
Abstract: Metal-organic microporous materials (MOMs) have attracted wide scientific attention owing to their unusual structure and properties, as well as commercial interest due to their potential applications in storage, separation and heterogeneous catalysis. One of the advantages of MOMs compared to other microporous materials, such as activated carbons, is their ability to exhibit a variety of pore surface properties such as hydrophilicity and chirality, as a result of the controlled incorporation of organic functional groups into the pore walls. This capability means that the pore surfaces of MOMs could be designed to adsorb specific molecules; but few design strategies for the adsorption of small molecules have been established so far. Here we report high levels of selective sorption of acetylene molecules as compared to a very similar molecule, carbon dioxide, onto the functionalized surface of a MOM. The acetylene molecules are held at a periodic distance from one another by hydrogen bonding between two non-coordinated oxygen atoms in the nanoscale pore wall of the MOM and the two hydrogen atoms of the acetylene molecule. This permits the stable storage of acetylene at a density 200 times the safe compression limit of free acetylene at room temperature.
TL;DR: This tutorial review focuses on the hydrogen bonding type arrangements for dynamic porous coordination polymers exhibiting elastic guest accommodations, in contrast to rigid three-dimensional (3-D) frameworks.
Abstract: In a decade, many porous coordination polymers have been synthesized, providing a variety of properties ranging from storage, separation, exchange of guests in their cavities, magnetism, conductivity and catalysis by their frameworks. In this tutorial review, we focus on the hydrogen bonding type arrangements for dynamic porous coordination polymers exhibiting elastic guest accommodations, in contrast to rigid three-dimensional (3-D) frameworks. Such dynamic porous properties induce highly-selective guest accommodation and magnetic modulation, and could now be considered a new class of practical materials.
TL;DR: In this article, neutralization of circulating IL-2 by anti-IL-2 monoclonal antibody for a limited period elicits autoimmune gastritis in BALB/c mice.
Abstract: Interleukin (IL)-2 plays a crucial role in the maintenance of natural immunologic self-tolerance. Neutralization of circulating IL-2 by anti-IL-2 monoclonal antibody for a limited period elicits autoimmune gastritis in BALB/c mice. Similar treatment of diabetes-prone nonobese diabetic mice triggers early onset of diabetes and produces a wide spectrum of T cell-mediated autoimmune diseases, including gastritis, thyroiditis, sialadenitis, and notably, severe neuropathy. Such treatment selectively reduces the number of Foxp3-expressing CD25(+) CD4(+) T cells, but not CD25(-) CD4(+) T cells, in the thymus and periphery of normal and thymectomized mice. IL-2 neutralization inhibits physiological proliferation of peripheral CD25(+) CD4(+) T cells that are presumably responding to normal self-antigens, whereas it is unable to inhibit their lymphopenia-induced homeostatic expansion in a T cell-deficient environment. In normal naive mice, CD25(low) CD4(+) nonregulatory T cells actively transcribe the IL-2 gene and secrete IL-2 protein in the physiological state. IL-2 is thus indispensable for the peripheral maintenance of natural CD25(+) CD4(+) regulatory T cells (T reg cells). The principal physiological source of IL-2 for the maintenance of T reg cells appears to be other T cells, especially CD25(low) CD4(+) activated T cells, which include self-reactive T cells. Furthermore, impairment of this negative feedback loop via IL-2 can be a cause and a predisposing factor for autoimmune disease.
TL;DR: It is shown by conditionally deleting beta-catenin in limb and head mesenchyme that beta- catenin is required for osteoblast lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes.
TL;DR: It is proposed that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and can switch IL-10–producing regulatory Th cell responses into TNF-α–producing inflammatory Th cell responds.
Abstract: We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4 + T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor- α (TNF- α ), but no interleukin (IL)-10 Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12 TSLP-induced OX40L on DCs was required for triggering naive CD4 + T cells to produce IL-4, -5, and -13 We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF- α , but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12–induced Th1 cell inflammation by promoting TNF- α , while inhibiting IL-10 We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10–producing regulatory Th cell responses into TNF- α –producing inflammatory Th cell responses
TL;DR: It is shown that Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation.
Abstract: Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring cells. Here we show that Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.
TL;DR: This review will emphasize how biomolecules released from gelatin controlled-release systems are able to retain their biological activity, allowing for their use in tissue engineering, therapeutic angiogenesis, gene therapy, and drug delivery applications.
TL;DR: It is shown that a single dose of Ngal, introduced during the initial phase of the disease, dramatically protects the kidney and mitigates azotemia, and it provides a unique method for their treatment.
Abstract: Neutrophil gelatinase-associated lipocalin (Ngal), also known as siderocalin, forms a complex with iron-binding siderophores (Ngal:siderophore:Fe). This complex converts renal progenitors into epithelial tubules. In this study, we tested the hypothesis that Ngal:siderophore:Fe protects adult kidney epithelial cells or accelerates their recovery from damage. Using a mouse model of severe renal failure, ischemia-reperfusion injury, we show that a single dose of Ngal (10 microg), introduced during the initial phase of the disease, dramatically protects the kidney and mitigates azotemia. Ngal activity depends on delivery of the protein and its siderophore to the proximal tubule. Iron must also be delivered, since blockade of the siderophore with gallium inhibits the rescue from ischemia. The Ngal:siderophore:Fe complex upregulates heme oxygenase-1, a protective enzyme, preserves proximal tubule N-cadherin, and inhibits cell death. Because mouse urine contains an Ngal-dependent siderophore-like activity, endogenous Ngal might also play a protective role. Indeed, Ngal is highly accumulated in the human kidney cortical tubules and in the blood and urine after nephrotoxic and ischemic injury. We reveal what we believe to be a novel pathway of iron traffic that is activated in human and mouse renal diseases, and it provides a unique method for their treatment.
TL;DR: GZ-B is one of the key mechanisms through which CD4-CD25+ Treg induce cell contact-mediated suppression, and appears to be mediated, in part, by the induction of apoptosis in the CD4+CD25− effector cell.
Abstract: CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppression by Treg is shown by the reduced ability of Treg from GZ-B-/- mice to suppress as efficiently as Treg from WT mice. GZ-B-mediated suppression is perforin independent, because suppression by Treg from perforin-/- and WT is indistinguishable. Additionally, suppression mediated by Treg appears to be mediated, in part, by the induction of apoptosis in the CD4+CD25- effector cell. In summary, GZ-B is one of the key mechanisms through which CD4+CD25+ Treg induce cell contact-mediated suppression.
TL;DR: A new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins.
Abstract: We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.
TL;DR: It is revealed that G9a and GLP cooperatively exert H3-K9 methyltransferase function in vivo, likely through the formation of higher-order heteromeric complexes.
Abstract: Histone H3 Lys 9 (H3-K9) methylation is a crucial epigenetic mark for transcriptional silencing. G9a is the major mammalian H3-K9 methyltransferase that targets euchromatic regions and is essential for murine embryogenesis. There is a single G9a-related methyltransferase in mammals, called GLP/Eu-HMTase1. Here we show that GLP is also important for H3-K9 methylation of mouse euchromatin. GLP-deficiency led to embryonic lethality, a severe reduction of H3-K9 mono- and dimethylation, the induction of Mage-a gene expression, and HP1 relocalization in embryonic stem cells, all of which were phenotypes of G9a-deficiency. Furthermore, we show that G9a and GLP formed a stoichiometric heteromeric complex in a wide variety of cell types. Biochemical analyses revealed that formation of the G9a/GLP complex was dependent on their enzymatic SET domains. Taken together, our new findings revealed that G9a and GLP cooperatively exert H3-K9 methyltransferase function in vivo, likely through the formation of higher-order heteromeric complexes.
TL;DR: In the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals.
Abstract: We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells ( approximately 90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation ( approximately 35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or Islet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals.
TL;DR: The problem of how to control the unusual properties of compounds with fluorine substituents deserves much attention, so as to promote the design of facile, efficient, and environmentally benign methods for the synthesis of valuable organofluorine targets.
Abstract: Fluorine has come to be recognized as a key element in materials science: in heat-transfer agents, liquid crystals, dyes, surfactants, plastics, elastomers, membranes, and other materials. Furthermore, many fluorine-containing biologically active agents are finding applications as pharmaceuticals and agrochemicals. Progress in synthetic fluorine chemistry has been critical to the development of these fields and has led to the invention of many novel fluorinated molecules as future drugs and materials. As a result of the electronic effects of fluorine substituents, fluorinated substrates and reagents often exhibit unusual and unique chemical properties, which often make them incompatible with established synthetic methods. Thus, the problem of how to control the unusual properties of compounds with fluorine substituents deserves much attention, so as to promote the design of facile, efficient, and environmentally benign methods for the synthesis of valuable organofluorine targets.
TL;DR: This study identifies tricellulin, the first integral membrane protein that is concentrated at the vertically oriented TJ strands of tricellular contacts, and indicates the critical function of tricedllulin for formation of the epithelial barrier.
Abstract: For epithelia to function as barriers, the intercellular space must be sealed. Sealing two adjacent cells at bicellular tight junctions (bTJs) is well described with the discovery of the claudins. Yet, there are still barrier weak points at tricellular contacts, where three cells join together. In this study, we identify tricellulin, the first integral membrane protein that is concentrated at the vertically oriented TJ strands of tricellular contacts. When tricellulin expression was suppressed with RNA interference, the epithelial barrier was compromised, and tricellular contacts and bTJs were disorganized. These findings indicate the critical function of tricellulin for formation of the epithelial barrier.
University of Tokyo1, Boston University2, Brookhaven National Laboratory3, University of California, Irvine4, California State University, Dominguez Hills5, Chonnam National University6, Duke University7, George Mason University8, Gifu University9, Indiana University10, University of Tsukuba11, Okayama University12, Kobe University13, Kyoto University14, Los Alamos National Laboratory15, Louisiana State University16, University of Maryland, College Park17, University of Minnesota18, Miyagi University of Education19, Stony Brook University20, Nagoya University21, Niigata University22, Osaka University23, Seoul National University24, Shizuoka University25, Sungkyunkwan University26, Tohoku University27, Tokai University28, Tokyo Institute of Technology29, University of Warsaw30, University of Washington31
TL;DR: In this article, a combined analysis of fully-contained, partially-contained and upward-going muon atmospheric neutrino data from a 1489 d exposure of the Super-Kamiokande detector is presented.
Abstract: We present a combined analysis of fully-contained, partially-contained and upward-going muon atmospheric neutrino data from a 1489 d exposure of the Super-Kamiokande detector. The data samples span roughly five decades in neutrino energy, from 100 MeV to 10 TeV. A detailed Monte Carlo comparison is described and presented. The data is fit to the Monte Carlo expectation, and is found to be consistent with neutrino oscillations of {nu}{sub {mu}}{r_reversible}{nu}{sub {tau}} with sin{sup 2}2{theta}>0.92 and 1.5x10{sup -3}<{delta}m{sup 2}<3.4x10{sup -3} eV{sup 2} at 90% confidence level.
TL;DR: Enantioselective reactions catalyzed by urea and thiourea derivatives as general acid catalysts as well as diastereoselectives reactions are described.
Abstract: Hydrogen-bonding interaction plays a crucial role in the molecular recognition and activation processes of various biologically important reactions that are mediated by enzymes and antibodies in living organisms. Recently, it has been shown that a hydrogen-bonding donor can be used as a general acid catalyst for various types of reactions in organic chemistry. In this article, we describe enantioselective reactions catalyzed by urea and thiourea derivatives as general acid catalysts as well as diastereoselective reactions. This perspective provides an overview of this rapidly growing field.
TL;DR: It is shown that bile acids promote glucagon-like peptide-1 (GLP-1) secretion through TGR5 in a murine enteroendocrine cell line STC-1, and an adenylate cyclase inhibitor, MDL12330A, significantly suppressed bile acid-promoted GLP- 1 secretion.
TL;DR: Forty-eight Gy of 3D stereotactic radiotherapy in 4 fractions using a stereOTactic body frame is useful for the treatment of Stage I lung tumors.
Abstract: Purpose: To evaluate the clinical outcomes of 48 Gy of three-dimensional stereotactic radiotherapy in four fractions for treating Stage I lung cancer using a stereotactic body frame. Methods and Materials: Forty-five patients who were treated between September 1998 and February 2004 were included in this study. Thirty-two patients had Stage IA lung cancer, and the other 13 had Stage IB lung cancer where tumor size was less than 4 cm in diameter. Three-dimensional treatment planning using 6–10 noncoplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 Gy. All patients were irradiated using a stereotactic body frame and received four single 12 Gy high doses of radiation at the isocenter over 5–13 (median = 12) days. Results: Seven tumors (16%) completely disappeared after treatment (CR) and 38 tumors (84%) decreased in size by 30% or more (PR). Therefore, all tumors showed local response. During the follow-up of 6–71 (median = 30) months, no pulmonary complications greater than an National Cancer Institute-Common Toxicity Criteria of Grade 3 were noted. No other vascular, cardiac, esophageal, or neurologic toxicities were encountered. Forty-four (98%) of 45 tumors were locally controlled during the follow-up period. However, regional recurrences and distant metastases occurred in 3 and 5 of T1 patients and zero and 4 of T2 patients, respectively. For Stage IA lung cancer, the disease-free survival and overall survival rates after 1 and 3 years were 80% and 72%, and 92% and 83%, respectively, whereas for Stage IB lung cancer, the disease-free survival and overall survival rates were 92% and 71%, and 82% and 72%, respectively. Conclusion: Forty-eight Gy of 3D stereotactic radiotherapy in 4 fractions using a stereotactic body frame is useful for the treatment of Stage I lung tumors.
TL;DR: Elastography is a promising imaging technique that can assist in the differential diagnosis of thyroid gland cancer, and the usefulness of these criteria was not considered to be high because of their low sensitivity.
Abstract: PURPOSE: To prospectively evaluate the elastographic appearance of thyroid gland tumors and explore the potential sensitivity and specificity of ultrasonographic (US) elastography for differentiating benign and malignant tumors, with histopathologic analysis as the reference standard. MATERIALS AND METHODS: The study was institutional review board approved, and each patient gave written informed consent. Fifty-two thyroid gland lesions (22 malignant, 30 benign) in 31 consecutive patients (six men, 25 women; mean age, 49.7 years ± 14.7 [standard deviation]) were examined with real-time elastography in the elasticity imaging mode implemented on a clinical US scanner modified for research. In addition, the radiofrequency echo data stored during US were exported from the scanner and used for off-line strain image reconstruction. All elastograms were evaluated for the lesion visibility, relative brightness, and margin regularity and definition by using a four-point scale. In addition, normal thyroid gland tiss...