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2. Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosis

Author

Bomsztyk, Joshua, Ravichandran, Sriram, Giles, Hannah V., Wright, Nicola, Berlanga, Oscar, Khwaja, Jahanzaib, Mahmood, Shameem, Wisniowski, Brendan, Cohen, Oliver, Foard, Darren, Gilbertson, Janet, Rauf, Muhammad U., Starr, Neasa, Martinez-Naharro, Ana, Venneri, Lucia, Whelan, Carol, Fontana, Marianna, Hawkins, Philip N., Gillmore, Julian D., Lachmann, Helen, Harding, Stephen, Pratt, Guy, and Wechalekar, Ashutosh D.

Published
2024
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3. Prevalence of smoldering multiple myeloma based on nationwide screening

Author

Thorsteinsdóttir, Sigrún, Gíslason, Gauti K., Aspelund, Thor, Rögnvaldsson, Sæmundur, Óskarsson, Jón Þórir, Sigurðardóttir, Guðrún Á, Þórðardóttir, Ásdís R., Viðarsson, Brynjar, Önundarson, Páll T., Agnarsson, Bjarni A., Sigurðardóttir, Margrét, Þorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Eyþórsson, Elías, Jónsson, Ásbjörn, Berlanga, Oscar, Hultcrantz, Malin, Durie, Brian G. M., Löve, Thorvardur J., Harding, Stephen, Landgren, Ola, and Kristinsson, Sigurður Y.

Published
2023
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4. Author Correction: Prevalence of smoldering multiple myeloma based on nationwide screening

Author

Thorsteinsdóttir, Sigrún, Gíslason, Gauti K., Aspelund, Thor, Rögnvaldsson, Sæmundur, Óskarsson, Jón Þórir, Sigurðardóttir, Guðrún Á, Þórðardóttir, Ásdís R., Viðarsson, Brynjar, Önundarson, Páll T., Agnarsson, Bjarni A., Sigurðardóttir, Margrét, Þorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Eyþórsson, Elías, Jónsson, Ásbjörn, Berlanga, Oscar, Hultcrantz, Malin, Durie, Brian G. M., Löve, Thorvardur J., Harding, Stephen, Landgren, Ola, and Kristinsson, Sigurður Y.

Published
2023
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5. Time to next treatment is longer in patients with a haematological complete response who are FLC-MS negative vs. positive

Author

Bomsztyk, Joshua, primary, Ravichandran, Sriram, primary, V, Hannah, primary, Wright, Nicola, primary, Berlanga, Oscar, primary, Khwaja, Jahanzaib, primary, Mahmood, Shameem, primary, Cohen, Oliver, primary, Foard, Darren, primary, Gilbertson, Janet, primary, U, Muhammad, primary, Martinez-Naharro, Ana, primary, Venneri, Lucia, primary, Whelan, Carol, primary, Fontana, Marianna, primary, Hawkins, Philip, primary, Lachmann, Helen, primary, Harding, Stephen, primary, Pratt, Guy, primary, and Wechalekar, Ashutosh, primary

Published
2024
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7. Expression and functional characterisation of the collagen receptor glycoprotein VI

Author

Berlanga, Oscar and Watson, Stephen P.

Subjects
572, Glycoproteins, Collagen
Abstract

This thesis is concerned with the study of the collagen receptor glycoprotein VI (GPVI). GPVI has been studied in a number of human haematopoietic cell lines and found to be expressed only in those showing mekaryocytic features. Moreover, differentiation of the human cell lines HEL and CMK to a megakaryocytic lineage using the phorbol ester PMA revealed upregulation of GPVI together with the associated FcR γ-chain. Further, primary cultures of mouse marrow cells demonstrated up-regulation of GPVI towards the end of differentiation, therefore confirming data obtained with cell lines and pointing to GPVI as a possible marker of megakaryocytic differentiation. Structure/function studies of GPVI were carried out by means of transient and stable transfection of the receptor into COS-7 or K562 cells. These studies demonstrated the necessity of the transmembrane argine and the cytoplasmic tail of GPVI for association to the FcR γ-chain. Lack of association or absence of FcR γ-chain rendered GPVI unable to signal, despite binding to convulxin, a GPVI-specific ligand which causes activation of the receptor. K562 cells expressing GPVI and the FcR γ-chain were able to reconstitute the proximal but not distal events in GPVI signaling. A detailed analysis demonstrated impairment in phosphorylation and translocation of SLP-76 to the membrane, despite the presence and activation of others proteins known to be necessary for this phosphorylation/translocation to occur. Stable expression of GPVI in K562 cells, which display low levels of expression of the collagen receptors α2βl and CD36, does not confer signaling properties in response to collagen. However, the cells respond to a collagen related peptide (CRP) which is specific for GPVI and to the snake venoms convulxin, alborhagin and alboaggregin-A, demonstrating that GPVI is one important component through which these venoms are acting.

Published
2001

8. Transient M-Proteins: Epidemiology, Causes, and the Impact of Mass Spectrometry: The Istopmm Study

Author

Palmason, Robert, primary, Berlanga, Oscar, additional, Sigurdsson, Jon Kristinn, additional, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Ekberg, Sara, additional, Crowther, Michael, additional, Levy, Marina, additional, Reed, Elin Ruth, additional, Oskarsson, Jon Þórir, additional, Sigurdardottir, Gudrun Asta, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Sigurdsson, Fridbjorn, additional, Olafsson, Isleifur, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Palsson, Runolfur, additional, Indridason, Olafur Skuli, additional, Aspelund, Thor, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Sverrisdottir, Ingigerdur Solveig, additional, Steingrimsdottir, Hlif, additional, Einarsson Long, Thorir, additional, Hultcrantz, Malin, additional, Landgren, Ola, additional, Harding, Stephen, additional, Durie, Brian G.M., additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2022
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9. Use of Matrix-Assisted Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Free Light Chain Assessment for the Diagnosis and Monitoring of Systemic Immunoglobulin Light Chain (AL) Amyloidosis

Author

Bomsztyk, Joshua, primary, Ravichandran, Sriram, additional, Giles, Hannah Victoria, additional, Berlanga, Oscar, additional, Harding, Stephen, additional, Khwaja, Jahanzaib, additional, Mahmood, Shameem, additional, Wisniowski, Brendan, additional, Cohen, Oliver C, additional, Foard, Darren, additional, Gilbertson, Janet, additional, Martinez De Azcona Naharro, Ana, additional, Venneri, Lucia, additional, Whelan, Carol, additional, Fontana, Marianna, additional, Hawkins, Philip N, additional, Gillmore, Julian D, additional, Lachmann, Helen J, additional, Pratt, Guy, additional, and Wechalekar, Ashutosh D., additional

Published
2022
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10. Implications and Prognostic Impact of Mass Spectrometry in Patients with Newly-Diagnosed Multiple Myeloma

Author

Mai, Elias K, primary, Huhn, Stefanie, additional, Miah, Kaya, additional, Poos, Alexandra M, additional, Scheid, Christof, additional, Weisel, Katja, additional, Bertsch, Uta, additional, Munder, Markus, additional, Berlanga, Oscar, additional, Hose, Dirk, additional, Seckinger, Anja, additional, Jauch, Anna, additional, Blau, Igor Wolfgang, additional, Haenel, Mathias, additional, Salwender, Hans, additional, Benner, Axel, additional, Raab, Marc S, additional, Goldschmidt, Hartmut, additional, and Weinhold, Niels, additional

Published
2022
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11. Implications and Prognostic Impact of Mass Spectrometry in Patients with Newly-Diagnosed Multiple Myeloma

Author

Mai, Elias K., Huhn, Stefanie, Miah, Kaya, Poos, Alexandra M., Scheid, Christof, Weisel, Katja, Bertsch, Uta, Munder, Markus, Berlanga, Oscar, Hose, Dirk, Seckinger, Anja, Jauch, Anna, Blau, Igor Wolfgang, Haenel, Mathias, Salwender, Hans, Benner, Axel, Raab, Marc S., Goldschmidt, Hartmut, Weinhold, Niels, Mai, Elias K., Huhn, Stefanie, Miah, Kaya, Poos, Alexandra M., Scheid, Christof, Weisel, Katja, Bertsch, Uta, Munder, Markus, Berlanga, Oscar, Hose, Dirk, Seckinger, Anja, Jauch, Anna, Blau, Igor Wolfgang, Haenel, Mathias, Salwender, Hans, Benner, Axel, Raab, Marc S., Goldschmidt, Hartmut, and Weinhold, Niels

Published
2022

22. Expression and functional characterisation of the collagen receptor glycoprotein VI

Author

Berlanga, O, Berlanga, Oscar, and Watson, S

Subjects
Collagen, Glycoproteins
Abstract

This thesis is concerned with the study of the collagen receptor glycoprotein VI (GPVI). GPVI has been studied in a number of human haematopoietic cell lines and found to be expressed only in those showing mekaryocytic features. Moreover, differentiation of the human cell lines HEL and CMK to a megakaryocytic lineage using the phorbol ester PMA revealed upregulation of GPVI together with the associated FcR γ-chain. Further, primary cultures of mouse marrow cells demonstrated up-regulation of GPVI towards the end of differentiation, therefore confirming data obtained with cell lines and pointing to GPVI as a possible marker of megakaryocytic differentiation. Structure/function studies of GPVI were carried out by means of transient and stable transfection of the receptor into COS-7 or K562 cells. These studies demonstrated the necessity of the transmembrane argine and the cytoplasmic tail of GPVI for association to the FcR γ-chain. Lack of association or absence of FcR γ-chain rendered GPVI unable to signal, despite binding to convulxin, a GPVI-specific ligand which causes activation of the receptor. K562 cells expressing GPVI and the FcR γ-chain were able to reconstitute the proximal but not distal events in GPVI signaling. A detailed analysis demonstrated impairment in phosphorylation and translocation of SLP-76 to the membrane, despite the presence and activation of others proteins known to be necessary for this phosphorylation/translocation to occur. Stable expression of GPVI in K562 cells, which display low levels of expression of the collagen receptors α2βl and CD36, does not confer signaling properties in response to collagen. However, the cells respond to a collagen related peptide (CRP) which is specific for GPVI and to the snake venoms convulxin, alborhagin and alboaggregin-A, demonstrating that GPVI is one important component through which these venoms are acting.

Published
2016

27. Multi-Center Clinical Validation of a Mass Spectrometry Immunoassay for the Diagnosis and Monitoring of Multiple Myeloma and Associated Disorders

Author

Berlanga, Oscar, Birtwistle, Jane, Allen, Syreeta, Malin, Gemma, Simion, Cristina, El-Khoury, Habib, Colchie, Julia, Bertamini, Luca, Fleming, Grace, Horowitz, Erica M., Ghobrial, Irene M., McLendon, Kaleb B, Roback, John, Neish, Andrew S, Grewal, Sarah K, and Lakos, Gabriella

Abstract

Introduction:Mass spectrometry (MS) technology holds great promise for the investigation of monoclonal proteins (M proteins) in peripheral blood. We present results from a multi-center clinical validation study using quantitative immunoprecipitation MS (QIP-MS). QIP-MS combines isotype-specific immunopurification with matrix-assisted laser-desorption ionization MS, and offers automated, sensitive detection, isotyping and quantification of M proteins. It reports the mass/charge ratio (m/z)of the involved light chain, which serves as molecular fingerprint for monitoring the M protein.

Published
2023
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29. Expression and functional characterisation of the collagen receptor glycoprotein VI

Author

Berlanga, Oscar., Watson, Stephen P., and Steve Watson

Subjects
Collagen, Glycoproteins
Abstract

This thesis is concerned with the study of the collagen receptor glycoprotein VI (GPVI). GPVI has been studied in a number of human haematopoietic cell lines and found to be expressed only in those showing mekaryocytic features. Moreover, differentiation of the human cell lines HEL and CMK to a megakaryocytic lineage using the phorbol ester PMA revealed upregulation of GPVI together with the associated FcR γ-chain. Further, primary cultures of mouse marrow cells demonstrated up-regulation of GPVI towards the end of differentiation, therefore confirming data obtained with cell lines and pointing to GPVI as a possible marker of megakaryocytic differentiation. Structure/function studies of GPVI were carried out by means of transient and stable transfection of the receptor into COS-7 or K562 cells. These studies demonstrated the necessity of the transmembrane argine and the cytoplasmic tail of GPVI for association to the FcR γ-chain. Lack of association or absence of FcR γ-chain rendered GPVI unable to signal, despite binding to convulxin, a GPVI-specific ligand which causes activation of the receptor. K562 cells expressing GPVI and the FcR γ-chain were able to reconstitute the proximal but not distal events in GPVI signaling. A detailed analysis demonstrated impairment in phosphorylation and translocation of SLP-76 to the membrane, despite the presence and activation of others proteins known to be necessary for this phosphorylation/translocation to occur. Stable expression of GPVI in K562 cells, which display low levels of expression of the collagen receptors α2βl and CD36, does not confer signaling properties in response to collagen. However, the cells respond to a collagen related peptide (CRP) which is specific for GPVI and to the snake venoms convulxin, alborhagin and alboaggregin-A, demonstrating that GPVI is one important component through which these venoms are acting.

Published
2001

37. The Role of ITAM- and ITIM-coupled Receptors in Platelet Activation by Collagen

Author

Asazuma, Naoki, primary, Atkinson, Ben, primary, Berlanga, Oscar, primary, Best, Denise, primary, Bobe, Regis, primary, Jarvis, Gavin, primary, Marshall, Stuart, primary, Snell, Daniel, primary, Stafford, Margaret, primary, Tulasne, David, primary, Wilde, Jonathan, primary, Wonerow, Peter, primary, Frampton, Jon, primary, and Watson, Steve, additional

Published
2001
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40. Interaction of Linker for Activation of T Cells with Multiple Adapter Proteins in Platelets Activated by the Glycoprotein VI-selective Ligand, Convulxin

Author

Asazuma, Naoki, primary, Wilde, Jonathan I., additional, Berlanga, Oscar, additional, Leduc, Mireille, additional, Leo, Albrecht, additional, Schweighoffer, Edina, additional, Tybulewicz, Victor, additional, Bon, Cassian, additional, Liu, Stan K., additional, McGlade, C. Jane, additional, Schraven, Burkhart, additional, and Watson, Steve P., additional

Published
2000
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42. Correlación del agua corporal con la resistencia a la insulina en ancianos.

Author

Romo, Miguel Angel Mendoza, Arriola, María Cleofas Ramírez, Rubio, Marco Vinicio González, Esqueda, Francisco López, Jasso, Juan José Medina, and Berlanga, Oscar Osvaldo Ortega

Subjects
INSULIN resistance, GLUCOSE, DIABETES, OBESITY
Abstract

Copyright of Medicina Interna de Mexico is the property of Colegio de Medicina Interna de Mexico and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2009

43. Update on collagen receptor interactions in platelets: is the two-state model still valid?

Author

Watson, Steve, Berlanga, Oscar, Best, Denise, and Frampton, Jon

Subjects
*BLOOD platelets, *COLLAGEN, *GLYCOPROTEINS
Abstract

This review summarises some of the key developments that have taken place in our understanding of platelet-collagen interactions within the last 18 months. Within this time, the major activatory collagen receptor glycoprotein VI (GPVI) has been sequenced and shown to reconstitute collagen responses in a megakaryocytic cell line. It is a member of the Ig superfamily of proteins, with two extracellular Ig domains, and is constitutively associated with the Fc receptor γ-chain (FcR γ-chain). GPVI signals through a pathway that shares many features with those of immune receptors, with critical roles for Syk and the adapters LAT and SLP-76 in the activation of PLCγ2. Significant developments have also taken place in regard to the role of the major adhesion receptor for collagen, the integrin α2β1 (also known as GPIa-IIa). An α2β1-selective collagen-based peptide has been developed and co-crystalisalised with the I-domain of the α2 subunit. Polymorphisms in α2 have been shown to cause wide variation in expression of α2β1, with the α2 allele T[sub 807]/A[sub 873] leading to a high level of the integrin and increased risk of stroke in young people. Activation of platelets by a wide range of agonists has been shown to increase the affinity of α2β1 to intermediate or high affinity states. This has important implications for the two-site, two-state model of collagen-platelet interactions. A new model is proposed in which collagen binds initially to either α2β1 or GPVI, leading to subsequent binding to the other receptor and conversion of the integrin to a high affinity state. In this model, both receptors generate intracellular signals which support platelet activation. [ABSTRACT FROM AUTHOR]

Published
2000
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45. The deployment of adenovirus-containing gene activated matrices onto severed axons after central nervous system injury leads to transgene expression in target neuronal cell bodies.

Author

Gonzalez AM, Berlanga O, Leadbeater WE, Cooper-Charles L, Sims K, Logan A, Eliceiri B, Berry M, and Baird A

Subjects
Animals, Axons pathology, Cell Line, Cell Survival, DNA, Viral metabolism, Green Fluorescent Proteins metabolism, Humans, Optic Nerve pathology, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Wistar, Retinal Ganglion Cells metabolism, Retinal Ganglion Cells pathology, Adenoviridae genetics, Axons metabolism, Biocompatible Materials metabolism, Central Nervous System pathology, Genetic Therapy, Transcriptional Activation, Transgenes genetics
Abstract

Background: In previous studies, we showed that gene activated matrices (GAMs) containing nonviral vectors successfully deliver genes to neurons after optic nerve and spinal cord injury. In the present study, we evaluated whether adenoviral vectors delivered within a GAM increase the efficiency of local gene delivery to injured CNS neurons. Lyophilized GAMs containing collagen and adenoviral vectors were assessed in vitro and in vivo., Methods: We evaluated viral vector stability, release kinetics and efficiency of transduction for this GAM formulation in vitro using the quantitative polymerase chain reaction (qPCR), flow cytometry and fluorescence microscopy. Using PCR, reverse transcriptase-PCR and confocal microscopy, we assessed viral DNA retrograde axonal transport, green fluorescent protein (GFP) expression in retinal ganglion cells (RGCs) after GAM implantation into the wound of the rat transected optic nerve., Results: qPCR analyses demonstrated that 100% of viral particles were retained within the collagen after lyophilization. In vitro studies demonstrated that 60% of the particles within the GAM were infective and not released from the collagen matrix when placed in water. By 24 h, GFP expression was detected within cells that have invaded the GAM. In vivo studies demonstrated that adenoviral particles were retrogradely transported in axons from the GAM implanted at the lesion site to the RGC in the retina where the corresponding mRNA was expressed. Analysis of the efficiency of cell transduction indicated that 69% of RGC express GFP., Conclusions: These studies demonstrate that lyophilized GAMs containing adenoviral particles within collagen are stable, retain a significant proportion of their infectivity and successfully and efficiently deliver genes to neurons after central nervous system injury.

Published
2009
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46. Glycoprotein VI oligomerization in cell lines and platelets.

Author

Berlanga O, Bori-Sanz T, James JR, Frampton J, Davis SJ, Tomlinson MG, and Watson SP

Subjects
Base Sequence, Cell Line, DNA Primers, Electrophoresis, Polyacrylamide Gel, Humans, Biopolymers metabolism, Blood Platelets metabolism, Platelet Membrane Glycoproteins metabolism
Abstract

Background: Glycoprotein VI (GPVI) is a physiologic receptor for collagen expressed at the surface of platelets and megakaryocytes. Constitutive dimerization of GPVI has been proposed as being necessary for the interaction with collagen, although direct evidence of dimerization has not been reported in cell lines or platelets., Objectives: To investigate oligomerization of GPVI in transfected cell lines and in platelets under non-stimulated conditions., Methods and Results: By using a combination of molecular and biochemical techniques, we demonstrate that GPVI association occurs at the surface of transfected 293T cells under basal conditions, through an interaction at the extracellular domain of the receptor. Bioluminescence resonance energy transfer was used to confirm oligomerization of GPVI under these conditions. A chemical crosslinker was used to detect constitutive oligomeric forms of GPVI at the surface of platelets, which contain the Fc receptor (FcR) gamma-chain., Conclusions: The present results directly demonstrate GPVI-FcR gamma-chain oligomerization at the surface of the platelet, and thereby add to the growing evidence that oligomerization of GPVI may be a prerequisite for binding of the receptor to collagen, and therefore for proper functioning of platelets upon vascular damage.

Published
2007
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47. The Fc receptor gamma-chain is necessary and sufficient to initiate signalling through glycoprotein VI in transfected cells by the snake C-type lectin, convulxin.

Author

Berlanga O, Tulasne D, Bori T, Snell DC, Miura Y, Jung S, Moroi M, Frampton J, and Watson SP

Subjects
Animals, Arginine metabolism, Binding Sites, COS Cells metabolism, Calcium metabolism, Chlorocebus aethiops, Collagen pharmacology, Crotalid Venoms genetics, Enzyme Precursors metabolism, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells metabolism, K562 Cells drug effects, K562 Cells metabolism, Phosphorylation, Protein-Tyrosine Kinases metabolism, Signal Transduction physiology, Syk Kinase, Transfection, Tumor Cells, Cultured, Carrier Proteins pharmacology, Crotalid Venoms pharmacology, Lectins, C-Type, Peptides, Platelet Membrane Glycoproteins metabolism, Receptors, Fc metabolism, Signal Transduction drug effects
Abstract

There is extensive evidence that FcR gamma-chain couples to the collagen receptor glycoprotein VI (GPVI) and becomes phosphorylated on tyrosines upon receptor cross-linking. However, it is not established whether this receptor complex is sufficient to initiate the signalling cascade. We transfected GPVI and the FcR gamma-chain into the human erythroleukaemia cell line K562, which lacks detectable expression of GPVI and the FcR gamma-chain. The results show that GPVI is unable to signal when expressed alone, despite its surface expression, upon stimulation with the snake C-type lectin, convulxin. Coexpression of the FcR gamma-chain confers signalling properties on the receptor. Furthermore, cotransfection of the FcR gamma-chain and two mutant versions of GPVI shows that the transmembrane arginine and cytoplasmic tail of GPVI are necessary for association with the FcR gamma-chain. These results demonstrate that reconstitution of the GPVI-FcR gamma-chain complex in cells expressing the necessary signalling network is sufficient to initiate signalling events in response to convulxin and collagen-related peptide.

Published
2002
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