There is significant need for effective medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory insult. To address these performance characteristics, we have generated a synthetic adhesive biomaterial inspired by the protein glues of marine mussels. In-vivo performance was interrogated in a murine model of extrahepatic syngeneic islet transplantation, as an alternative to standard portal administration. The adhesive precursor polymer consisted of a branched poly(ethylene glycol) (PEG) core, whose endgroups were derivatized with catechol, a functional group abundant in mussel adhesive proteins. Under oxidizing conditions, adhesive hydrogels formed in less than 1min from catechol-derivatized PEG (cPEG) solutions. Upon implantation, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue for up to one year. In-situ cPEG adhesive formation was shown to efficiently immobilize transplanted islets at the epididymal fat pad and external liver surfaces, permitting normoglycemic recovery and graft revascularization. These findings establish the use of synthetic, biologically-inspired adhesives for islet transplantation at extrahepatic sites. Brubaker, C. E. Kissler, H. Wang, L. J. Kaufman, D. B. Messersmith, P. B. 0 2009-10-10T06:15:47Z 2009-10-06 2009-10-09 %0 Journal Article %A Brubaker, C. E. %A Kissler, H. %A Wang, L. J. %A Kaufman, D. B. %A Messersmith, P. B. %D 2010 %T Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation. %J Biomaterials %V 31 %N 3 %P 420-427 %M 19811819 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19811819 %X There is significant need for effective medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory insult. To address these performance characteristics, we have generated a synthetic adhesive biomaterial inspired by the protein glues of marine mussels. In-vivo performance was interrogated in a murine model of extrahepatic syngeneic islet transplantation, as an alternative to standard portal administration. The adhesive precursor polymer consisted of a branched poly(ethylene glycol) (PEG) core, whose endgroups were derivatized with catechol, a functional group abundant in mussel adhesive proteins. Under oxidizing conditions, adhesive hydrogels formed in less than 1 min from catechol-derivatized PEG (cPEG) solutions. Upon implantation, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue for up to one year. In-situ cPEG adhesive formation was shown to efficiently immobilize transplanted islets at the epididymal fat pad and external liver surfaces, permitting normoglycemic recovery and graft revascularization. These findings establish the use of synthetic, biologically-inspired adhesives for islet transplantation at extrahepatic sites. %+ Biomedical Engineering Department, Northwestern University, Evanston, IL 60208, USA. 8465 false false 3 Biomaterials Biomaterials 420-427 2010-01-01 ppublish JOURNAL ARTICLE 19811819 In-Process 2009-11-18T07:17:30Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19811819 31 2010 Pancreatic islet encapsulation within semi-permeable materials has been proposed for transplantation therapy of type I diabetes mellitus. Polymer hydrogel networks used for this purpose have been shown to provide protection from islet destruction by immunoreactive cells and antibodies. However, one of the fundamental deficiencies with current encapsulation methods is that the permselective barriers cannot protect islets from cytotoxic molecules of low molecular weight that are diffusible into the capsule material, which subsequently results in beta-cell destruction. Use of materials that can locally inhibit the interaction between the permeable small cytotoxic factors and islet cells may prolong the viability and function of encapsulated islet grafts. Here we report the design of anti-inflammatory hydrogels supporting islet cell survival in the presence of diffusible pro-inflammatory cytokines. We demonstrated that a poly(ethylene glycol)-containing hydrogel network, formed by native chemical ligation and presenting an inhibitory peptide for islet cell surface IL-1 receptor, was able to maintain the viability of encapsulated islet cells in the presence of a combination of cytokines including IL-1beta, TNF-alpha, and INF-gamma. In stark contrast, cells encapsulated in unmodified hydrogels were mostly destroyed by cytokines which diffused into the capsules. At the same time, these peptide-modified hydrogels were able to efficiently protect encapsulated cells against beta-cell specific T-lymphocytes and maintain glucose-stimulated insulin release by islet cells. With further development, the approach of encapsulating cells and tissues within hydrogels presenting anti-inflammatory agents may represent a new strategy to improve cell and tissue graft function in transplantation and tissue engineering applications. Su, J. Hu, B. H. Lowe, W. L. Jr Kaufman, D. B. Messersmith, P. B. 0 2009-09-30T06:15:41Z 2009-09-25 2009-09-29 %0 Journal Article %A Su, J. %A Hu, B. H. %A Lowe, W. L. Jr %A Kaufman, D. B. %A Messersmith, P. B. %D 2010 %T Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation. %J Biomaterials %V 31 %N 2 %P 308-314 %M 19782393 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19782393 %X Pancreatic islet encapsulation within semi-permeable materials has been proposed for transplantation therapy of type I diabetes mellitus. Polymer hydrogel networks used for this purpose have been shown to provide protection from islet destruction by immunoreactive cells and antibodies. However, one of the fundamental deficiencies with current encapsulation methods is that the permselective barriers cannot protect islets from cytotoxic molecules of low molecular weight that are diffusible into the capsule material, which subsequently results in beta-cell destruction. Use of materials that can locally inhibit the interaction between the permeable small cytotoxic factors and islet cells may prolong the viability and function of encapsulated islet grafts. Here we report the design of anti-inflammatory hydrogels supporting islet cell survival in the presence of diffusible pro-inflammatory cytokines. We demonstrated that a poly(ethylene glycol)-containing hydrogel network, formed by native chemical ligation and presenting an inhibitory peptide for islet cell surface IL-1 receptor, was able to maintain the viability of encapsulated islet cells in the presence of a combination of cytokines including IL-1 beta, TNF-alpha, and INF-gamma. In stark contrast, cells encapsulated in unmodified hydrogels were mostly destroyed by cytokines which diffused into the capsules. At the same time, these peptide-modified hydrogels were able to efficiently protect encapsulated cells against beta-cell specific T-lymphocytes and maintain glucose-stimulated insulin release by islet cells. With further development, the approach of encapsulating cells and tissues within hydrogels presenting anti-inflammatory agents may represent a new strategy to improve cell and tissue graft function in transplantation and tissue engineering applications. %+ Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA. 8416 false false 2 Biomaterials Biomaterials 308-314 2010-01-01 ppublish JOURNAL ARTICLE 19782393 In-Process 2009-11-11T07:23:05Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19782393 31 2010 Klippel-Feil syndrome (KFS) is a rare congenital abnormality characterized by a short neck, a low posterior hairline, and limited head movement. Occasionally, patients with KFS may also show signs of deafness, intellectual disability, cardiac malformation, palpebral ptosis, facial nerve paralysis, cleft palate, and scoliosis. Although some researchers have documented this syndrome, scant attention has been paid to craniomaxillofacial manifestations and dental treatment of patients with KFS. The objective of this case report was to describe the planning and execution of dental treatment for a 10-year-old male patient with KFS. de Deus Moura de Lima, M. Ortega, K. L. Araujo, L. C. Soares, M. M. de Magalhaes, M. H. 0 2009-11-07T07:17:49Z 2009-11-06 %0 Journal Article %A de Deus Moura de Lima, M. %A Ortega, K. L. %A Araujo, L. C. %A Soares, M. M. %A de Magalhaes, M. H. %D 2009 %T Dental team management for a patient with Klippel-Feil syndrome: Case report. %J Spec Care Dentist %V 29 %N 6 %P 244-248 %M 19886936 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19886936 %X Klippel-Feil syndrome (KFS) is a rare congenital abnormality characterized by a short neck, a low posterior hairline, and limited head movement. Occasionally, patients with KFS may also show signs of deafness, intellectual disability, cardiac malformation, palpebral ptosis, facial nerve paralysis, cleft palate, and scoliosis. Although some researchers have documented this syndrome, scant attention has been paid to craniomaxillofacial manifestations and dental treatment of patients with KFS. The objective of this case report was to describe the planning and execution of dental treatment for a 10-year-old male patient with KFS. %+ Postgraduate Student, Special Care Dentistry Center, Department of Oral Pathology, University of Sao Paulo, Sao Paulo, Brazil. de Deus Moura de Lima, Marina Ortega, Karem Lopez Araujo, Luis Carlos Arias Soares, Marcelo Melo de Magalhaes, Marina Helena Cury Gallottini 8570 false false 6 Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry Spec Care Dentist 244-248 ppublish Journal Article 19886936 In-Data-Review 2009-11-07T07:17:49Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19886936 29 2009 Cell-to-cell variability of gene expression in clonal populations of mammalian cells is ubiquitous. However, because molecular biologists habitually assume uniformity of the cell populations that serve as starting material for experimental analysis, attention to such non-genetic heterogeneity has been scant. As awareness of, and interest in, understanding its biological significance increases, this Primer attempts to clarify the confusing terminologies used in an emerging field that often conflates heterogeneity with noise, and provides a qualitative introduction to the fundamental dynamic principles that underlie heterogeneity. It thus aims to present a useful conceptual framework to organize, analyze and communicate observations made at the resolution of individual cells that indicate that heterogeneity of cell populations plays a biological role, such as in multipotency and cell fate decision. Huang, S. 0 2009-11-14T07:16:29Z 2009-11-13 %0 Journal Article %A Huang, S. %D 2009 %T Non-genetic heterogeneity of cells in development: more than just noise. %J Development %V 136 %N 23 %P 3853-3862 %M 19906852 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19906852 %X Cell-to-cell variability of gene expression in clonal populations of mammalian cells is ubiquitous. However, because molecular biologists habitually assume uniformity of the cell populations that serve as starting material for experimental analysis, attention to such non-genetic heterogeneity has been scant. As awareness of, and interest in, understanding its biological significance increases, this Primer attempts to clarify the confusing terminologies used in an emerging field that often conflates heterogeneity with noise, and provides a qualitative introduction to the fundamental dynamic principles that underlie heterogeneity. It thus aims to present a useful conceptual framework to organize, analyze and communicate observations made at the resolution of individual cells that indicate that heterogeneity of cell populations plays a biological role, such as in multipotency and cell fate decision. %+ Institute for Biocomplexity and Informatics, Biological Sciences Bldg, Room 539D, University of Calgary, Calgary, AB T3A 0Y1, Canada. sui.huang@ucalgary.ca Huang, Sui 8591 false false 23 Development (Cambridge, England) Development 3853-3862 2009-12-01 ppublish Journal Article 19906852 In-Process 2009-11-14T07:16:29Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19906852 136 2009 In the 1970s, several human retinoblastoma cell lines were developed from cultures of primary tumors. As the human retinoblastoma cell lines were established in culture, growth properties and changes in cell adhesion were described. Those changes correlated with the ability of the human retinoblastoma cell lines to invade the optic nerve and metastasize in orthotopic xenograft studies. However, the mechanisms that underly these changes were not determined. We have used the recently developed knockout mouse models of retinoblastoma to begin to characterize the molecular, cellular and genetic changes associated with retinoblastoma tumor progression and optic nerve invasion. Here we present the isolation and characterization of the first mouse retinoblastoma cell lines with targeted deletions of the Rb family. Our detailed analysis of these cells as they were propagated in culture from the primary tumor show that changes in cadherin-mediated cell adhesion are associated with retinoblastoma invasion of the optic nerve prior to metastasis. In addition, the same changes in cadherin-mediated cell adhesion correlate with the invasive properties of the human retinoblastoma cell lines isolated decades ago providing a molecular mechanism for these earlier observations. Most importantly, our studies are in agreement with genetic studies on human retinoblastomas suggesting that changes in this pathway are involved in tumor progression. Laurie, N. Mohan, A. McEvoy, J. Reed, D. Zhang, J. Schweers, B. Ajioka, I. Valentine, V. Johnson, D. Ellison, D. Dyer, M. A. 0 2009-10-01T06:13:58Z 2009-09-28 2009-09-30 %0 Journal Article %A Laurie, N. %A Mohan, A. %A McEvoy, J. %A Reed, D. %A Zhang, J. %A Schweers, B. %A Ajioka, I. %A Valentine, V. %A Johnson, D. %A Ellison, D. %A Dyer, M. A. %D 2009 %T Changes in retinoblastoma cell adhesion associated with optic nerve invasion. %J Mol Cell Biol %V 29 %N 23 %P 6268-6282 %M 19786571 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19786571 %X In the 1970s, several human retinoblastoma cell lines were developed from cultures of primary tumors. As the human retinoblastoma cell lines were established in culture, growth properties and changes in cell adhesion were described. Those changes correlated with the ability of the human retinoblastoma cell lines to invade the optic nerve and metastasize in orthotopic xenograft studies. However, the mechanisms that underlie these changes were not determined. We used the recently developed knockout mouse models of retinoblastoma to begin to characterize the molecular, cellular, and genetic changes associated with retinoblastoma tumor progression and optic nerve invasion. Here we report the isolation and characterization of the first mouse retinoblastoma cell lines with targeted deletions of the Rb family. Our detailed analysis of these cells as they were propagated in culture from the primary tumor shows that changes in cadherin-mediated cell adhesion are associated with retinoblastoma invasion of the optic nerve prior to metastasis. In addition, the same changes in cadherin-mediated cell adhesion correlate with the invasive properties of the human retinoblastoma cell lines isolated decades ago, providing a molecular mechanism for these earlier observations. Most importantly, our studies are in agreement with genetic studies on human retinoblastomas, suggesting that changes in this pathway are involved in tumor progression. %+ Department of Developmental Neurobiology, MS 323, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. 8422 false false 23 Molecular and cellular biology Mol Cell Biol 6268-6282 2009-12-01 ppublish JOURNAL ARTICLE 19786571 In-Process 2009-11-10T07:18:39Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19786571 29 2009 Cyclocondensations of aromatic diamines with 1,1'-bis(2,4-dinitrophenyl)-4,4'-bipyridinium salts afford doubly or quadruply charged, macrocyclic, N,N'-diarylbipyridinium cations. These are tolerant of a wide range of acids, bases, and nucleophiles, although they appear to undergo reversible, one-electron reduction by tertiary amines. Single-crystal X-ray analysis demonstrates the presence of a macrocycle conformation in which the 4,4'-bipyridinium and 4,4'-biphenylenedisulfonyl residues are suitably spaced and aligned for complexation with pi-donor arenes, and NMR studies in solution indeed confirm binding to 1,5-bis[hydroxy(ethoxy)ethoxy]naphthalene. Colquhoun, H. M. Greenland, B. W. Zhu, Z. Shaw, J. S. Cardin, C. J. Burattini, S. Elliott, J. M. Basu, S. Gasa, T. B. Stoddart, J. F. 0 2009-10-30T06:23:27Z 2009-10-29 %0 Journal Article %A Colquhoun, H. M. %A Greenland, B. W. %A Zhu, Z. %A Shaw, J. S. %A Cardin, C. J. %A Burattini, S. %A Elliott, J. M. %A Basu, S. %A Gasa, T. B. %A Stoddart, J. F. %D 2009 %T A general synthesis of macrocyclic pi-electron-acceptor systems. %J Org Lett %V 11 %N 22 %P 5238-5241 %M 19860397 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19860397 %X Cyclocondensations of aromatic diamines with 1,1'-bis(2,4-dinitrophenyl)-4,4'-bipyridinium salts afford doubly or quadruply charged, macrocyclic, N,N'-diarylbipyridinium cations. These are tolerant of a wide range of acids, bases, and nucleophiles, although they appear to undergo reversible, one-electron reduction by tertiary amines. Single-crystal X-ray analysis demonstrates the presence of a macrocycle conformation in which the 4,4'-bipyridinium and 4,4'-biphenylenedisulfonyl residues are suitably spaced and aligned for complexation with pi-donor arenes, and NMR studies in solution indeed confirm binding to 1,5-bis[hydroxy(ethoxy)ethoxy]naphthalene. %+ Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AH, UK. h.m.colquhoun@rdg.ac.uk 8542 false false 22 Organic letters Org Lett 5238-5241 2009-11-19 ppublish JOURNAL ARTICLE 19860397 In-Process 2009-11-13T07:20:48Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19860397 11 2009 2-(((3R,4R)-4-(Allyloxy)-1-benzylpyrrolidin-3-yl)methyl)-6-(2,5-dimethyl-1 H-pyrrol-1-yl)-4-methylpyridine (2), a key intermediate for the preparation of novel neuronal nitric oxide synthase (nNOS) inhibitors, is synthesized using diisopropyl (R)-(+)-malate as the starting material. The key steps involve a Frater-Seebach diastereoselective alkylation and a fast intramolecular cyclization. Xue, F. Gu, W. Silverman, R. B. 0 2009-10-30T06:22:46Z 2009-10-29 %0 Journal Article %A Xue, F. %A Gu, W. %A Silverman, R. B. %D 2009 %T Concise route to the chiral pyrrolidine core of selective inhibitors of neuronal nitric oxide. %J Org Lett %V 11 %N 22 %P 5194-5197 %M 19860389 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19860389 %X 2-(((3R,4R)-4-(Allyloxy)-1-benzylpyrrolidin-3-yl)methyl)-6-(2,5-dimethyl-1 H-pyrrol-1-yl)-4-methylpyridine (2), a key intermediate for the preparation of novel neuronal nitric oxide synthase (nNOS) inhibitors, is synthesized using diisopropyl (R)-(+)-malate as the starting material. The key steps involve a Frater-Seebach diastereoselective alkylation and a fast intramolecular cyclization. %+ Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA. 8540 false false 22 Organic letters Org Lett 5194-5197 2009-11-19 ppublish JOURNAL ARTICLE 19860389 In-Process 2009-11-13T07:20:07Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19860389 11 2009 Binary mixtures of C(20)BAS and POPC membranes were studied by solid-state (2)H NMR spectroscopy and small angle x-ray scattering (SAXS) over a wide range of concentrations and at different temperatures. Three specifically deuterated C(20)BAS derivatives--[1',1',20',20'-(2)H(4)]C(20)BAS, [2',2',19',19'-(2)H(4)]C(20)BAS, and [10',11'-(2)H(2)]C(20)BAS--combined with protiated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as membranes containing POPC-d(31) and fully protiated bolalipid, were used in NMR experiments to obtain structural information for the mixtures. The (2)H NMR spectra of [10',11'-(2)H(2)]C(20)BAS/POPC membrane dispersions reveal that the bolalipid is predominantly in the transmembrane conformation at high bolalipid concentrations (100, 90, and 70 mol %). At < or =50 mol % C(20)BAS, smaller quadrupolar couplings appear in the spectra, indicating the presence of U-shaped conformers. The proportion of U-shaped bolalipids increases as the amount of POPC in the membrane increases; however, the transmembrane component remains the dominant bolalipid conformation in the membrane even at 45 degrees C and 10 mol % C(20)BAS, where it accounts for approximately 50% of the bolalipid population. The large fraction of C(20)BAS transmembrane conformers, regardless of the C(20)BAS/POPC ratio, together with the findings from molecular mean-field theory calculations, suggests the coexistence of phase-separated bolalipid-rich domains and POPC-rich domains. A single lamellar repeat distance was observed in SAXS experiments corresponding to the average repeat spacing expected for C(20)BAS- and POPC-rich domains. These observations are consistent with the presence of microphase-separated domains in the mixed membrane samples that arise from POPC-C(20)BAS hydrophobic mismatch. Brownholland, D. P. Longo, G. S. Struts, A. V. Justice, M. J. Szleifer, I. Petrache, H. I. Brown, M. F. Thompson, D. H. 0 2009-11-19T07:24:03Z 2009-11-18 %0 Journal Article %A Brownholland, D. P. %A Longo, G. S. %A Struts, A. V. %A Justice, M. J. %A Szleifer, I. %A Petrache, H. I. %A Brown, M. F. %A Thompson, D. H. %D 2009 %T Phase separation in binary mixtures of bipolar and monopolar lipid dispersions revealed by 2H NMR spectroscopy, small angle x-ray scattering, and molecular theory. %J Biophys J %V 97 %N 10 %P 2700-2709 %M 19917223 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19917223 %X Binary mixtures of C(20)BAS and POPC membranes were studied by solid-state (2)H NMR spectroscopy and small angle x-ray scattering (SAXS) over a wide range of concentrations and at different temperatures. Three specifically deuterated C(20)BAS derivatives--[1',1',20',20'-(2)H(4)]C(20)BAS, [2',2',19',19'-(2)H(4)]C(20)BAS, and [10',11'-(2)H(2)]C(20)BAS--combined with protiated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as membranes containing POPC-d(31) and fully protiated bolalipid, were used in NMR experiments to obtain structural information for the mixtures. The (2)H NMR spectra of [10',11'-(2)H(2)]C(20)BAS/POPC membrane dispersions reveal that the bolalipid is predominantly in the transmembrane conformation at high bolalipid concentrations (100, 90, and 70 mol %). At < or =50 mol % C(20)BAS, smaller quadrupolar couplings appear in the spectra, indicating the presence of U-shaped conformers. The proportion of U-shaped bolalipids increases as the amount of POPC in the membrane increases; however, the transmembrane component remains the dominant bolalipid conformation in the membrane even at 45 degrees C and 10 mol % C(20)BAS, where it accounts for approximately 50% of the bolalipid population. The large fraction of C(20)BAS transmembrane conformers, regardless of the C(20)BAS/POPC ratio, together with the findings from molecular mean-field theory calculations, suggests the coexistence of phase-separated bolalipid-rich domains and POPC-rich domains. A single lamellar repeat distance was observed in SAXS experiments corresponding to the average repeat spacing expected for C(20)BAS- and POPC-rich domains. These observations are consistent with the presence of microphase-separated domains in the mixed membrane samples that arise from POPC-C(20)BAS hydrophobic mismatch. %+ Department of Chemistry, Purdue University, West Lafayette, Indiana, USA. Brownholland, David P Longo, Gabriel S Struts, Andrey V Justice, Matthew J Szleifer, Igal Petrache, Horia I Brown, Michael F Thompson, David H 8609 false false 10 Biophysical journal Biophys J 2700-2709 2009-11-18 ppublish Journal Article 19917223 In-Data-Review 2009-11-19T07:24:03Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19917223 97 2009 Dense, hydrophobic coatings comprising hydrophilic nanoparticles are deposited rapidly from water/toluene emulsions. The process of deposition is driven by a subtle interplay between interfacial phenomena, electrostatic interparticle repulsions, and hydrogen bonding between the NPs and the substrate(s). The packing fractions and the plasmonic properties of the coatings can be controlled by the pH of the aqueous phase. Once formed, the coatings can be further functionalized without a loss of mechanical integrity. Kowalczyk, B. Apodaca, M. M. Soh, S. Grzybowski, B. A. 0 2009-10-28T06:23:05Z 2009-10-27 %0 Journal Article %A Kowalczyk, B. %A Apodaca, M. M. %A Soh, S. %A Grzybowski, B. A. %D 2009 %T Rapid deposition of hydrophobic nanoparticle monolayers onto hydrophilic surfaces from liquid-liquid interfaces. %J Langmuir %V 25 %N 22 %P 12855-12859 %M 19852509 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19852509 %X Dense, hydrophobic coatings comprising hydrophilic nanoparticles are deposited rapidly from water/toluene emulsions. The process of deposition is driven by a subtle interplay between interfacial phenomena, electrostatic interparticle repulsions, and hydrogen bonding between the NPs and the substrate(s). The packing fractions and the plasmonic properties of the coatings can be controlled by the pH of the aqueous phase. Once formed, the coatings can be further functionalized without a loss of mechanical integrity. %+ Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA. 8533 false false 22 Langmuir : the ACS journal of surfaces and colloids Langmuir 12855-12859 2009-11-17 ppublish JOURNAL ARTICLE 19852509 In-Process 2009-11-13T07:20:40Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19852509 25 2009 PURPOSE: Recent studies suggest that children <24 months with stage I favorable histology Wilms tumors <550 g [very low risk Wilms tumors (VLRWT)] have an excellent prognosis when treated with nephrectomy only, without adjuvant chemotherapy. The identification of risk categories within VLRWT may enable refinement of their definition and optimization of their therapy. EXPERIMENTAL DESIGN: To define biologically distinct subsets, global gene expression analysis was done on 39 VLRWT that passed all quality-control parameters and the clusters identified were validated in an independent set of 11 VLRWT. Validation of select differentially expressed genes was done with immunohistochemistry on a tissue microarray from 20 of 39 tumors. Loss of heterozygosity (LOH) for 11p15, 1p, and 16q was analyzed in 52 tumors using PCR. RESULTS: Two distinctive clusters were identified. One cluster included 9 tumors with epithelial differentiated tubular histology, paucity of nephrogenic rests, lack of LOH for 1p, 16q, and 11p, absence of relapse, and a unique gene expression profile consistent with arrest following mesenchymal-to-epithelial transition. The second cluster included 13 tumors with mixed histology, intralobar nephrogenic rests, and decreased expression of WT1. Three of 6 relapses occurred in this cluster. Of 43 informative tumors, 11p LOH was present in 5 of 5 relapses and 11 of 38 nonrelapses. CONCLUSIONS: Two subsets comprising a total of 56% of VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable the refinement of clinical stratification and less arbitrary definition of VLRWT. (Clin Cancer Res 2009;15(22):6800-9). Sredni, S. T. Gadd, S. Huang, C. C. Breslow, N. Grundy, P. Green, D. M. Dome, J. S. Shamberger, R. C. Beckwith, J. B. Perlman, E. J. 0 2009-11-13T07:19:53Z 2009-11-10 2009-11-12 %0 Journal Article %A Sredni, S. T. %A Gadd, S. %A Huang, C. C. %A Breslow, N. %A Grundy, P. %A Green, D. M. %A Dome, J. S. %A Shamberger, R. C. %A Beckwith, J. B. %A Perlman, E. J. %D 2009 %T Subsets of very low risk wilms tumor show distinctive gene expression, histologic, and clinical features. %J Clin Cancer Res %V 15 %N 22 %P 6800-6809 %M 19903788 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19903788 %X PURPOSE: Recent studies suggest that children <24 months with stage I favorable histology Wilms tumors <550 g [very low risk Wilms tumors (VLRWT)] have an excellent prognosis when treated with nephrectomy only, without adjuvant chemotherapy. The identification of risk categories within VLRWT may enable refinement of their definition and optimization of their therapy. EXPERIMENTAL DESIGN: To define biologically distinct subsets, global gene expression analysis was done on 39 VLRWT that passed all quality-control parameters and the clusters identified were validated in an independent set of 11 VLRWT. Validation of select differentially expressed genes was done with immunohistochemistry on a tissue microarray from 20 of 39 tumors. Loss of heterozygosity (LOH) for 11p15, 1p, and 16q was analyzed in 52 tumors using PCR. RESULTS: Two distinctive clusters were identified. One cluster included 9 tumors with epithelial differentiated tubular histology, paucity of nephrogenic rests, lack of LOH for 1p, 16q, and 11p, absence of relapse, and a unique gene expression profile consistent with arrest following mesenchymal-to-epithelial transition. The second cluster included 13 tumors with mixed histology, intralobar nephrogenic rests, and decreased expression of WT1. Three of 6 relapses occurred in this cluster. Of 43 informative tumors, 11p LOH was present in 5 of 5 relapses and 11 of 38 nonrelapses. CONCLUSIONS: Two subsets comprising a total of 56% of VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable the refinement of clinical stratification and less arbitrary definition of VLRWT. %+ Departments of Pathology and Preventive Medicine, Northwestern University Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, Illinois, USA. 8589 false false 22 Clinical cancer research : an official journal of the American Association for Cancer Research Clin Cancer Res 6800-6809 2009-11-15 ppublish JOURNAL ARTICLE 19903788 In-Process 2009-11-17T07:21:12Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19903788 15 2009 A series of multithiol-functionalized free-base and Zn-coordinated porphyrazines (pz's) have been prepared and characterized as self-assembled monolayers (SAMs) on Au. The synthetic flexibility of the pz's provides a unique opportunity to tune their electronic and chemical characteristics and to control the distance of the redox-active pz macrocycle from the Au surface. This allows us to study the reduction potentials of these surface-bound pz's as a function of film thickness and molecular charge distribution using angle-resolved X-ray photoelectron spectroscopy and cyclic voltammetry. Upon SAM formation, the reduction potentials of all pz's show a significant positive shift from their formal potentials when free in solution (up to approximately +1 V), with the magnitude of the shift inversely related to the Au-pz distance as determined from the film thickness of the pz SAM (thicknesses ranging from 3.5 to 11.8 A). When the pz lies down on the surface, in a SAM of thickness approximately 3.5 A, the charge distribution within a pz macrocycle also plays a role in determining the potential shift. These observations are consistent with our originally proposed mechanism for potential shifts upon binding to a metal surface based on image charge effects and with the analysis of Liu and Newton (J. Phys. Chem. 1994, 98, 7162). Zong, H. Sun, P. Mirkin, C. A. Barrett, A. G. Hoffman, B. M. 0 2009-10-22T06:20:52Z 2009-10-21 %0 Journal Article %A Zong, H. %A Sun, P. %A Mirkin, C. A. %A Barrett, A. G. %A Hoffman, B. M. %D 2009 %T Varying the electrochemical potential and thickness of porphyrazine SAMs by molecular design. %J J Phys Chem B %V 113 %N 45 %P 14892-14903 %M 19839629 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19839629 %X A series of multithiol-functionalized free-base and Zn-coordinated porphyrazines (pz's) have been prepared and characterized as self-assembled monolayers (SAMs) on Au. The synthetic flexibility of the pz's provides a unique opportunity to tune their electronic and chemical characteristics and to control the distance of the redox-active pz macrocycle from the Au surface. This allows us to study the reduction potentials of these surface-bound pz's as a function of film thickness and molecular charge distribution using angle-resolved X-ray photoelectron spectroscopy and cyclic voltammetry. Upon SAM formation, the reduction potentials of all pz's show a significant positive shift from their formal potentials when free in solution (up to approximately +1 V), with the magnitude of the shift inversely related to the Au-pz distance as determined from the film thickness of the pz SAM (thicknesses ranging from 3.5 to 11.8 A). When the pz lies down on the surface, in a SAM of thickness approximately 3.5 A, the charge distribution within a pz macrocycle also plays a role in determining the potential shift. These observations are consistent with our originally proposed mechanism for potential shifts upon binding to a metal surface based on image charge effects and with the analysis of Liu and Newton (J. Phys. Chem. 1994, 98, 7162). %+ Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, USA. 8505 false false 45 The journal of physical chemistry. B J Phys Chem B 14892-14903 2009-11-12 ppublish JOURNAL ARTICLE 19839629 In-Process 2009-11-07T07:17:13Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19839629 113 2009 Sun, I. C. Eun, D. K. Na, J. H. Lee, S. Kim, I. J. Youn, I. C. Ko, C. Y. Kim, H. S. Lim, D. Choi, K. Messersmith, P. B. Park, T. G. Kim, S. Y. Kwon, I. C. Kim, K. Ahn, C. H. 0 2009-11-12T07:26:23Z 2009-11-09 2009-11-11 %0 Journal Article %A Sun, I. C. %A Eun, D. K. %A Na, J. H. %A Lee, S. %A Kim, I. J. %A Youn, I. C. %A Ko, C. Y. %A Kim, H. S. %A Lim, D. %A Choi, K. %A Messersmith, P. B. %A Park, T. G. %A Kim, S. Y. %A Kwon, I. C. %A Kim, K. %A Ahn, C. H. %D 2009 %T Heparin-Coated Gold Nanoparticles for Liver-Specific CT Imaging. %J Chemistry %M 19902441 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19902441 %+ Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791 (Korea), Fax: (+82) 2-958-5909. 8586 false false Chemistry (Weinheim an der Bergstrasse, Germany) Chemistry 2009-11-09 aheadofprint JOURNAL ARTICLE 19902441 Publisher 2009-11-12T07:26:23Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19902441 2009 Wei, Y. Bishop, K. J. Kim, J. Soh, S. Grzybowski, B. A. 0 2009-11-11T07:22:59Z 2009-11-07 2009-11-10 %0 Journal Article %A Wei, Y. %A Bishop, K. J. %A Kim, J. %A Soh, S. %A Grzybowski, B. A. %D 2009 %T Making Use of Bond Strength and Steric Hindrance in Nanoscale "Synthesis" %J Angew Chem Int Ed Engl %M 19899173 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19899173 %+ Department of Chemistry, Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (USA) http://dysa.northwestern.edu. 8581 false false Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl 2009-11-07 aheadofprint JOURNAL ARTICLE 19899173 Publisher 2009-11-11T07:22:59Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19899173 2009 Mechanically interlocked molecular (MIM) switches in the form of bistable [2]rotaxanes and [2]catenanes have proven to be-when incorporated in molecular electronic devices (MEDs) and in nanoelectromechanical systems (NEMS)-a realistic and viable alternative to the silicon chip density challenge. Structural modifications and chemical environment can have a large impact on the relaxation thermodynamics of the molecular motions, such as translation and circumrotation in bistable rotaxanes and catenanes responsible for the operation of devices based on MIMs. The effects of structural modifications on the difference in free energy (DeltaG(o)) for the equilibrium processes in switchable MIMs can be predicted by considering, firstly, the interactions present in their precursor pseudorotaxanes. By employing isothermal titration microcalorimetry (ITC) to investigate the thermodynamic parameters governing pseudorotaxane formation for a series of monosubstituted, acceptor host cyclophanes with various donor guests, in conjunction with X-ray crystallographic data, an obvious link between the noncovalent bonding interactions in pseudorotaxanes and MIMs that survive following the formation of the mechanical bond can be identified. It follows that the changes (DeltaDeltaG(o) values) in the difference of free energy during the formation of different pseudorotaxanes can subsequently be extrapolated to predict DeltaG(o) values for the thermodynamics associated with switching in analogous MIM switches, employing the same donor-acceptor recognition components. In this manner, a systematic and predictive thermodynamic approach to designing and tuning switchable MIMs and MIM-based materials has been established. Additionally, these thermodynamic relationships are reminiscent of the long forgotten concept of the 'parachor' as a molecular descriptor with respect to the additivity of physical properties in chemical systems dealing specifically with quantitative structure property-activity relationships (QSPR/QSAR). Olson, M. A. Braunschweig, A. B. Ikeda, T. Fang, L. Trabolsi, A. Slawin, A. M. Khan, S. I. Stoddart, J. F. 0 2009-10-17T06:20:07Z 2009-09-03 2009-10-16 %0 Journal Article %A Olson, M. A. %A Braunschweig, A. B. %A Ikeda, T. %A Fang, L. %A Trabolsi, A. %A Slawin, A. M. %A Khan, S. I. %A Stoddart, J. F. %D 2009 %T Thermodynamic forecasting of mechanically interlocked switches. %J Org Biomol Chem %V 7 %N 21 %P 4391-4405 %M 19830288 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19830288 %X Mechanically interlocked molecular (MIM) switches in the form of bistable [2]rotaxanes and [2]catenanes have proven to be--when incorporated in molecular electronic devices (MEDs) and in nanoelectromechanical systems (NEMS)--a realistic and viable alternative to the silicon chip density challenge. Structural modifications and chemical environment can have a large impact on the relaxation thermodynamics of the molecular motions, such as translation and circumrotation in bistable rotaxanes and catenanes responsible for the operation of devices based on MIMs. The effects of structural modifications on the difference in free energy (DeltaG(o)) for the equilibrium processes in switchable MIMs can be predicted by considering, firstly, the interactions present in their precursor pseudorotaxanes. By employing isothermal titration microcalorimetry (ITC) to investigate the thermodynamic parameters governing pseudorotaxane formation for a series of monosubstituted, acceptor host cyclophanes with various donor guests, in conjunction with X-ray crystallographic data, an obvious link between the noncovalent bonding interactions in pseudorotaxanes and MIMs that survive following the formation of the mechanical bond can be identified. It follows that the changes (DeltaDeltaG(o) values) in the difference of free energy during the formation of different pseudorotaxanes can subsequently be extrapolated to predict DeltaG(o) values for the thermodynamics associated with switching in analogous MIM switches, employing the same donor-acceptor recognition components. In this manner, a systematic and predictive thermodynamic approach to designing and tuning switchable MIMs and MIM-based materials has been established. Additionally, these thermodynamic relationships are reminiscent of the long forgotten concept of the 'parachor' as a molecular descriptor with respect to the additivity of physical properties in chemical systems dealing specifically with quantitative structure property-activity relationships (QSPR/QSAR). %+ Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, USA. Olson, Mark A Braunschweig, Adam B Ikeda, Taichi Fang, Lei Trabolsi, Ali Slawin, Alexandra M Z Khan, Saeed I Stoddart, J Fraser 8489 false false 21 Organic & biomolecular chemistry Org Biomol Chem 4391-4405 2009-11-07 ppublish Journal Article 19830288 In-Process 2009-10-20T06:21:11Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19830288 7 2009 Chen, H. Pazicni, S. Krett, N. L. Ahn, R. W. Penner-Hahn, J. E. Rosen, S. T. O'Halloran, T. V. 0 2009-11-08T07:20:58Z 2009-11-05 2009-11-07 %0 Journal Article %A Chen, H. %A Pazicni, S. %A Krett, N. L. %A Ahn, R. W. %A Penner-Hahn, J. E. %A Rosen, S. T. %A O'Halloran, T. V. %D 2009 %T Coencapsulation of Arsenic- and Platinum-based Drugs for Targeted Cancer Treatment. %J Angew Chem Int Ed Engl %V 48 %N 49 %P 9295-9299 %M 19894238 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19894238 %+ Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 (USA), Fax: (+1) 847-491-7713. 8575 false false 49 Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl 9295-9299 2009-11-05 aheadofprint JOURNAL ARTICLE 19894238 Publisher 2009-11-18T07:16:22Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19894238 48 2009 A method for the oxidative alkylation of ketones through intramolecular allyl-group transfer within preformed allyldimethylsilyl enol ethers is reported. A number of examples are detailed, including a study into the effects of resident sterocenters within cyclic enol ethers. Konkol, L. C. Jones, B. T. Thomson, R. J. 0 2009-11-07T07:17:55Z 2009-11-04 2009-11-06 %0 Journal Article %A Konkol, L. C. %A Jones, B. T. %A Thomson, R. J. %D 2009 %T Oxidative Carbon-Carbon Bond Formation via Allyldimethylsilyl Enol Ethers. %J Org Lett %M 19888716 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19888716 %X A method for the oxidative alkylation of ketones through intramolecular allyl-group transfer within preformed allyldimethylsilyl enol ethers is reported. A number of examples are detailed, including a study into the effects of resident sterocenters within cyclic enol ethers. %+ Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208. 8571 false false Organic letters Org Lett 2009-11-04 aheadofprint JOURNAL ARTICLE 19888716 Publisher 2009-11-07T07:17:55Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19888716 2009 Tissue engineering scaffolds capable of gene delivery can provide a structure that supports tissue formation while also inducing the expression of inductive factors. Sustained release strategies are hypothesized to maintain elevated plasmid concentrations locally that can enhance gene transfer. In this report, we investigate the relationship between plasmid release kinetics and the extent and duration of transgene expression. Scaffolds were fabricated from polymer microspheres modified with cationic polymers (polyethylenimine, poly(l-lysine), poly(allylamine hydrochloride), polydiallyldimethylammonium) or polydopamine (PD), with PD enhancing incorporation and slowing release. In vivo implantation of scaffolds into the peritoneal fat pad had no significant changes in the level and duration of transgene expression between PD and unmodified scaffolds. Control studies with plasmid dried onto scaffolds, which exhibited a rapid release, and scaffolds with extended leaching to reduce initial quantities released had similar levels and duration of expression. Changing the plasmid design, from a cytomegalovirus (CMV) to an ubiquitin C (UbC) promoter substantially altered the duration of expression. These studies suggest that the initial dose released and vector design affect the extent and duration of transgene expression, which may be sustained over several weeks, potentially leading to numerous applications in cell transplantation and regenerative medicine. Aviles, M. O. Lin, C. H. Zelivyanskaya, M. Graham, J. G. Boehler, R. M. Messersmith, P. B. Shea, L. D. 0 2009-11-08T07:21:35Z 2009-11-03 2009-11-07 %0 Journal Article %A Aviles, M. O. %A Lin, C. H. %A Zelivyanskaya, M. %A Graham, J. G. %A Boehler, R. M. %A Messersmith, P. B. %A Shea, L. D. %D 2009 %T The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds. %J Biomaterials %M 19892398 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19892398 %X Tissue engineering scaffolds capable of gene delivery can provide a structure that supports tissue formation while also inducing the expression of inductive factors. Sustained release strategies are hypothesized to maintain elevated plasmid concentrations locally that can enhance gene transfer. In this report, we investigate the relationship between plasmid release kinetics and the extent and duration of transgene expression. Scaffolds were fabricated from polymer microspheres modified with cationic polymers (polyethylenimine, poly(l-lysine), poly(allylamine hydrochloride), polydiallyldimethylammonium) or polydopamine (PD), with PD enhancing incorporation and slowing release. In vivo implantation of scaffolds into the peritoneal fat pad had no significant changes in the level and duration of transgene expression between PD and unmodified scaffolds. Control studies with plasmid dried onto scaffolds, which exhibited a rapid release, and scaffolds with extended leaching to reduce initial quantities released had similar levels and duration of expression. Changing the plasmid design, from a cytomegalovirus (CMV) to an ubiquitin C (UbC) promoter substantially altered the duration of expression. These studies suggest that the initial dose released and vector design affect the extent and duration of transgene expression, which may be sustained over several weeks, potentially leading to numerous applications in cell transplantation and regenerative medicine. %+ Departments of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd, Evanston, IL 60208, USA. 8576 false false Biomaterials Biomaterials 2009-11-03 aheadofprint JOURNAL ARTICLE 19892398 Publisher 2009-11-08T07:21:35Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19892398 2009 We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is approximately 300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies. Shad Thaxton, C. Elghanian, R. Thomas, A. D. Stoeva, S. I. Lee, J. S. Smith, N. D. Schaeffer, A. J. Klocker, H. Horninger, W. Bartsch, G. Mirkin, C. A. 0 2009-10-22T06:21:20Z 2009-10-19 2009-10-21 %0 Journal Article %A Thaxton, C. S. %A Elghanian, R. %A Thomas, A. D. %A Stoeva, S. I. %A Lee, J. S. %A Smith, N. D. %A Schaeffer, A. J. %A Klocker, H. %A Horninger, W. %A Bartsch, G. %A Mirkin, C. A. %D 2009 %T Nanoparticle-based bio-barcode assay redefines "undetectable" PSA and biochemical recurrence after radical prostatectomy. %J Proc Natl Acad Sci U S A %V 106 %N 44 %P 18437-18442 %M 19841273 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19841273 %X We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is approximately 300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies. %+ Department of Urology, Northwestern University Feinberg School of Medicine, 303 East Chicago, Chicago, IL 60611, USA. cthaxton003@md.northwestern.edu 8510 false false 44 Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A 18437-18442 2009-11-03 ppublish JOURNAL ARTICLE 19841273 In-Process 2009-11-06T07:15:55Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19841273 106 2009 A new strut containing an imidazolium tetracarboxylic acid core has been successfully incorporated into a microporous material using paddlewheel-coordinated copper(II) ions as nodes. Sorption studies conducted on this permanently microporous material imply that it can separate carbon dioxide from methane with high selectivity. Lee, J. Y. Roberts, J. M. Farha, O. K. Sarjeant, A. A. Scheidt, K. A. Hupp, J. T. 0 2009-10-11T06:13:41Z 2009-10-10 %0 Journal Article %A Lee, J. Y. %A Roberts, J. M. %A Farha, O. K. %A Sarjeant, A. A. %A Scheidt, K. A. %A Hupp, J. T. %D 2009 %T Synthesis and gas sorption properties of a metal-azolium framework (MAF) material. %J Inorg Chem %V 48 %N 21 %P 9971-9973 %M 19813724 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19813724 %X A new strut containing an imidazolium tetracarboxylic acid core has been successfully incorporated into a microporous material using paddlewheel-coordinated copper(II) ions as nodes. Sorption studies conducted on this permanently microporous material imply that it can separate carbon dioxide from methane with high selectivity. %+ Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA. 8469 false false 21 Inorganic chemistry Inorg Chem 9971-9973 2009-11-02 ppublish JOURNAL ARTICLE 19813724 In-Process 2009-10-29T06:22:35Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19813724 48 2009 PURPOSE: To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection. MATERIALS AND METHODS: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration-time curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (v(e)). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM. RESULTS: Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K(trans) of 0.21 min(-1) +/- 0.14 (standard deviation) and an average v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L +/- 0.13. CONCLUSION: These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts. Jansen, S. A. Paunesku, T. Fan, X. Woloschak, G. E. Vogt, S. Conzen, S. D. Krausz, T. Newstead, G. M. Karczmar, G. S. 0 2009-10-31T06:20:35Z 2009-10-30 %0 Journal Article %A Jansen, S. A. %A Paunesku, T. %A Fan, X. %A Woloschak, G. E. %A Vogt, S. %A Conzen, S. D. %A Krausz, T. %A Newstead, G. M. %A Karczmar, G. S. %D 2009 %T Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model. %J Radiology %V 253 %N 2 %P 399-406 %M 19864527 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19864527 %X PURPOSE: To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection. MATERIALS AND METHODS: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration-time curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (v(e)). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM. RESULTS: Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K(trans) of 0.21 min(-1) +/- 0.14 (standard deviation) and an average v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L +/- 0.13. CONCLUSION: These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts. %+ Department of Radiology, University of Chicago, Chicago, IL 60637, USA. Jansen, Sanaz A Paunesku, Tatjana Fan, Xiaobing Woloschak, Gayle E Vogt, Stefan Conzen, Suzanne D Krausz, Thomas Newstead, Gillian M Karczmar, Gregory S 8548 false false 2 Radiology Radiology 399-406 2009-11-01 ppublish Journal Article 19864527 In-Process 2009-10-31T06:20:35Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19864527 253 2009