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Louis A Clark, Stephen J Demarest, John Eldredge, Matthew B Jarpe, You Li, Ken Simon, Herman W T van Vlijmen
A number of light and heavy chain canonical residue core redesigns were made in a therapeutic antibody (AQC2, anti-VLA1) Fab to explore the consequences to binding affinity and stability. These positions are all loop supporting, primarily CDR1 residues which do not directly contact the antigen. Structure based methods were used with and without consensus sequence information. 30 constructs were made, 24 expressed, and 70% of the designs using consensus sequence information retained binding affinity. Some success maintaining stability with more extreme redesigns suggests a surprising tolerance to mutation, though it often comes at the cost of loss of binding affinity and presumed loop conformation changes...
February 2014: Journal of Structural Biology
Leticia Coín Aragüez, Mora Murri, Wilfredo Oliva Olivera, Julian Salas, Maria Dolores Mayas, Javier Delgado-Lista, Francisco Tinahones, Rajaa El Bekay
Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelial growth factor (VEGF) production. Adult human thymus degenerates into fat tissue (thymus adipose tissue (TAT)). Recently, we described that TAT from cardiomyopathy ischemic subjects has angiogenic properties. The goal of our study was to analyze whether aging could also impair angiogenic properties in TAT as in other adipose tissue such as subcutaneous (subcutaneous adipose tissue (SAT)). SAT and TAT specimens were obtained from 35 patients undergoing cardiac surgery, making these tissues readily available as a prime source of adipose tissue...
August 2013: Age (2005-)
Jameel Dennis, Daniel T Meehan, Duane Delimont, Marisa Zallocchi, Greg A Perry, Stacie O'Brien, Hongmin Tu, Taina Pihlajaniemi, Dominic Cosgrove
Alport syndrome is a common hereditary basement membrane disorder caused by mutations in the collagen IV α3, α4, or α5 genes that results in progressive glomerular and interstitial renal disease. Interstitial monocytes that accumulate in the renal cortex from Alport mice are immunopositive for integrin α1β1, while only a small fraction of circulating monocytes are immunopositive for this integrin. We surmised that such a disparity might be due to the selective recruitment of α1β1-positive monocytes. In this study, we report the identification of collagen XIII as a ligand that facilitates this selective recruitment of α1β1 integrin-positive monocytes...
November 2010: American Journal of Pathology
Louis A Clark, P Ann Boriack-Sjodin, Eric Day, John Eldredge, Christopher Fitch, Matt Jarpe, Stephan Miller, You Li, Ken Simon, Herman W T van Vlijmen
A design approach was taken to investigate the feasibility of replacing single complementarity determining region (CDR) antibody loops. This approach may complement simpler mutation-based strategies for rational antibody design by expanding conformation space. Enormous crystal structure diversity is available, making CDR loops logical targets for structure-based design. A detailed analysis for the L1 loop shows that each loop length takes a distinct conformation, thereby allowing control on a length scale beyond that accessible to simple mutations...
February 2009: Protein Engineering, Design & Selection: PEDS
Mehri Ghafourian Boroujerdnia, Fatemeh Ghalambor Dezfuly, Nepton Emad Mosthophy, Rahim Chinipardaz
BACKGROUND: Recent attention has focused on the expression of integrin molecules within the endometrium, and their relation to infertility. OBJECTIVE: The present prospective study was undertaken to determine whether the endometrium of women with unexplained infertility differs in the expression of very late activation antigens (VLA) from the endometrium of normal fertile women. METHODS: Thirty samples of endometrial biopsies from hysterectomies with nonendometrial pathology and 28 endometrial samples by uterine curetting from infertile women in secretary phase at implantation time were collected, stained with three monoclonal antibodies against beta1 integrin subunits including VLA-1 to VLA-3 by immunohistochemical technique and then assessed semiquantitively by microscope...
December 2006: Iranian Journal of Immunology: IJI
Louis A Clark, P Ann Boriack-Sjodin, John Eldredge, Christopher Fitch, Bethany Friedman, Karl J M Hanf, Matthew Jarpe, Stefano F Liparoto, You Li, Alexey Lugovskoy, Stephan Miller, Mia Rushe, Woody Sherman, Kenneth Simon, Herman Van Vlijmen
Improving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate...
May 2006: Protein Science: a Publication of the Protein Society
H van Goor, W Coers, M L van der Horst, S Huitema, A J Suurmeijer
OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha-actinin, vinculin, beta-tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-61, beta1, beta2 [CD18], vitronectin receptor [alphavbeta3], CD 11b), leukocyte adhesion molecules (ICAM-1) and extracellular matrix proteins (collagen IV, fibronectin, laminin, vitronectin) in human and rat kidneys by using a superior processing and immunohistochemical staining technique...
October 2001: Analytical and Quantitative Cytology and Histology
E J Meharra, M Schön, D Hassett, C Parker, W Havran, H Gardner
Very late antigen 1 (VLA1) is an integrin collagen receptor that is expressed by lymphocytes in several disease states. VLA1 blockade has been shown to ameliorate gut disease in experimental graft-versus-host disease. Here we show that in the VLA1 null mouse, which is generally healthy, there is a 50% reduction in gut intraepithelial lymphocytes (IELs) despite an otherwise normal lymphocyte distribution in peripheral blood and lymphoid organs. The gammadelta to alphabeta ratios of IELs are unchanged. We also find that IL2-stimulated splenocytes from VLA1 null animals show a deficiency in adhesion to fibrillar and basement membrane collagen as well as reduced proliferation in response to collagen substratum...
April 10, 2000: Cellular Immunology
J Cernicharo, A Noriega-Crespo, D Cesarsky, B Lefloch, E González-Alfonso, F Najarro, E Dartois, S Cabrit
The formation and evolution of young low-mass stars are characterized by important processes of mass loss and accretion occurring in the innermost regions of their placentary circumstellar disks. Because of the large obscuration of these disks at optical and infrared wavelengths in the early protostellar stages (class 0 sources), they were previously detected only at radio wavelengths using interferometric techniques. We have detected with the Infrared Space Observatory the mid-infrared (mid-IR) emission associated with the class 0 protostar VLA1 in the HH1-HH2 region located in the Orion nebula...
April 28, 2000: Science
C Perrin, A Pisani, M Demarchez, J F Michiel, J P Ortonne
Immunohistological expression of VLA1-5 and alpha 6 beta 4 integrins have been studied in 21 cases of primary neuroendocrine carcinomas of the skin (NECS), three xenografts on nude mice and one NECS cell culture. The phenotypic properties of NECS cells were largely maintained in NECS grafted on athymic nude-mice and in the corresponding cell line. Our results indicate that alpha 1 beta 1 and to a lesser extent alpha 3 beta 1, alpha 5 beta 1 are the main integrins expressed in NECS. In addition, VLA2, 4 and alpha 6 beta 4 are heterogeneously expressed in the same group of tumors and very sparsely present...
June 1996: Journal of Cutaneous Pathology
M Miettinen, R Castello, E Wayner, R Schwarting
Integrins form a family of membrane-spanning cell-surface proteins that promote cell-cell or cell-matrix adhesion and integrate the pericellular matrix to the cytoskeleton. Integrins are believed to be involved in the differentiation of tissues during development. They are involved in the relationship of tumor cells to the matrix and may on the other hand reflect the differentiation status of cells. In this study, we evaluated immunohistochemically the distribution of VLA integrins (alpha 1 to alpha 6 chains of beta 1 integrins) in a representative selection of normal tissues and 110 solid tumors...
April 1993: American Journal of Pathology
H Iwasaki
A novel human CD7-positive leukemia cell line (HSM911) derived from the peripheral blood of a patient with acute myelogenous leukemia (AML) was studied for its cellular and biological characterization. Proliferation assay using a variety of cytokines demonstrated that the HSM911 cells proliferate in response to recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF), recombinant Interleukin-3 (rIL-3) and recombinant stem cell factor (rSCF), but do not in response to recombinant granulocyte-colony stimulating factor (rG-CSF), natural macrophage-colony stimulating factor (M-CSF), rIL-1, rIL-2, rIL-4, rIL-5, rIL-6 or recombinant erythropoietin (rEpo)...
July 1994: [Hokkaido Igaku Zasshi] the Hokkaido Journal of Medical Science
F Pandolfi, L Trentin, L A Boyle, I Stamenkovic, H R Byers, R B Colvin, J T Kurnick
The role of cell adhesion molecules (CAM) LFA1, ICAM-1, LFA3, VLA1, VLA4, CD29, CD44, and CD56 in tumor-infiltrating lymphocyte (TIL) and natural killer cell (NK)-mediated killing of target cells was studied. Melanoma cell lines and autologous TIL were derived from seven patients with metastatic melanoma, and cytotoxicity assays were done in the presence and absence of monoclonal antibodies (MoAb) to CAM expressed on melanoma cells or TIL. The melanoma cell lines analyzed were all positive for CD29 and LFA3 expression, negative for LFA1 expression, but showed variable expression of ICAM-1, VLA1, VLA4, CD44, and CD56...
March 1, 1992: Cancer
I A Denkers, T J de Jong-de Boer, R H Beelen, G J Ossenkoppele, M M Langenhuijsen
Acute myeloid leukaemia (AML) cells have a variable capacity to egress from bone marrow into peripheral blood. This may be due to a variable lack of adhesion molecules on leukaemic cells. The expression of VLA1, 3, 4, 5, 6, beta 1-chain, LFA1, beta 2-chain, ICAM1 and NCAM appeared to be higher in bone marrow as compared to peripheral blood leukaemic cells, although this only reached significance for beta 1-chain (p less than 0.01). The number of cases with more than 20% positive cells in bone marrow leukaemic cells was lower in immature FAB-subtypes (M1, M5a) as opposed to more mature subtypes (M2, M3, M4, M5b) for the adhesion molecules tested...
1992: Leukemia Research
I A Denkers, R H Beelen, G J Ossenkoppele, A J de Jong-de Boer, M M Langenhuijsen
Human long-term bone marrow cultures (HLTBMCs) were established with bone marrow samples collected from 15 patients with acute myeloid leukemia (AML) and compared with HLTBMCs from eight healthy volunteers. During 6 weeks of culture, the cellular composition of HLTBMCs was quantitatively studied. The cells of the HLTBMCs were divided into three main categories: fibroblasts, macrophages, and 'other cells' (endothelial cells, hematopoietic cells and undefined cells). HLTBMCs derived from healthy volunteers demonstrated a very consistent development...
May 1992: Annals of Hematology
P Douville, M F Seldin, S Carbonetto
The integrin alpha 1 chain (Vla1) associates with the beta 1 chain to form a heterodimer that functions as a dual laminin/collagen receptor in neural cells and hematopoietic cells. We have used an interspecies backcross gene-mapping technique to map the Vla1 gene to the distal end of chromosome 13 in the mouse genome. The Vla1 locus is located 3.5 cM distal to Ctla-3 and 7.8 cM distal to Htrla. We have further characterized this locus in recombinant inbred (RI) mice by examining the strain distribution patterns of nine genomic DNA restriction fragment length variants detected with alpha 1 cDNA probes...
October 1992: Genomics
K Rössler, C Neuchrist, K Kitz, O Scheiner, D Kraft, H Lassmann
The expression of leucocyte adhesion molecules was studied on cerebral endothelia by immunocytochemistry. In peritumoral "normal" brain tissue we found low endothelial expression of ICAM1, LFA3, CD44, and CD9, whereas VLA1 was present on vessels in high incidence and density. LFA1, CD2, and CR3 were found on intraluminal and parenchymal leucocytes, but were absent on brain vessels. In brain tumors and inflammatory brain lesions, we observed an up-regulation of endothelial ICAM1 and LFA3 expression, whereas other adhesion molecules on endothelial cells remained unchanged...
February 1992: Journal of Neuroscience Research
S Minafra, C Luparello, I Pucci-Minafra, M E Sobel, S Garbisa
Ductal infiltration carcinomas (d.i.c.) of the breast are potentially highly metastatic tumours, associated with drastic alterations of the architecture and molecular composition of the extracellular matrix at the tumour-host interface. 8701-BC, a recently characterized cell line, isolated from primary d.i.c., was used to study different aspects of tumor cell-substratum interactions. Since type V collagen deposition is augmented in d.i.c. we have examined the ability of 8701-BC cells to interact with this collagen species...
June 1992: Journal of Cell Science
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