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1.
Nat Commun ; 14(1): 6663, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37863892

ABSTRACT

Topological insulator phases of non-interacting particles have been generalized from periodic crystals to amorphous lattices, which raises the question whether topologically ordered quantum many-body phases may similarly exist in amorphous systems? Here we construct a soluble chiral amorphous quantum spin liquid by extending the Kitaev honeycomb model to random lattices with fixed coordination number three. The model retains its exact solubility but the presence of plaquettes with an odd number of sides leads to a spontaneous breaking of time reversal symmetry. We unearth a rich phase diagram displaying Abelian as well as a non-Abelian quantum spin liquid phases with a remarkably simple ground state flux pattern. Furthermore, we show that the system undergoes a finite-temperature phase transition to a conducting thermal metal state and discuss possible experimental realisations.

2.
Nat Commun ; 13(1): 3813, 2022 Jul 02.
Article in English | MEDLINE | ID: mdl-35780167

ABSTRACT

The S=3/2 Kitaev honeycomb model (KHM) is a quantum spin liquid (QSL) state coupled to a static Z2 gauge field. Employing an SO(6) Majorana representation of spin3/2's, we find an exact representation of the conserved plaquette fluxes in terms of static Z2 gauge fields akin to the S=1/2 KHM which enables us to treat the remaining interacting matter fermion sector in a parton mean-field theory. We uncover a ground-state phase diagram consisting of gapped and gapless QSLs. Our parton description is in quantitative agreement with numerical simulations, and is furthermore corroborated by the addition of a [001] single ion anisotropy (SIA) which continuously connects the gapless Dirac QSL of our model with that of the S=1/2 KHM. In the presence of a weak [111] SIA, we discuss an emergent chiral QSL within a perturbation theory.

3.
Phys Rev Lett ; 126(9): 097201, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33750154

ABSTRACT

The quasi-two-dimensional Mott insulator α-RuCl_{3} is proximate to the sought-after Kitaev quantum spin liquid (QSL). In a layer of α-RuCl_{3} on graphene, the dominant Kitaev exchange is further enhanced by strain. Recently, quantum oscillation (QO) measurements of such α-RuCl_{3} and graphene heterostructures showed an anomalous temperature dependence beyond the standard Lifshitz-Kosevich (LK) description. Here, we develop a theory of anomalous QO in an effective Kitaev-Kondo lattice model in which the itinerant electrons of the graphene layer interact with the correlated magnetic layer via spin interactions. At low temperatures, a heavy Fermi liquid emerges such that the neutral Majorana fermion excitations of the Kitaev QSL acquire charge by hybridizing with the graphene Dirac band. Using ab initio calculations to determine the parameters of our low-energy model, we provide a microscopic theory of anomalous QOs with a non-LK temperature dependence consistent with our measurements. We show how remnants of fractionalized spin excitations can give rise to characteristic signatures in QO experiments.

4.
Phys Rev Lett ; 119(17): 176601, 2017 Oct 27.
Article in English | MEDLINE | ID: mdl-29219477

ABSTRACT

We study the time evolution after a quantum quench in a family of models whose degrees of freedom are fermions coupled to spins, where quenched disorder appears neither in the Hamiltonian parameters nor in the initial state. Focusing on the behavior of entanglement, both spatial and between subsystems, we show that the model supports a state exhibiting combined area and volume-law entanglement, being characteristic of the quantum disentangled liquid. This behavior appears for one set of variables, which is related via a duality mapping to another set, where this structure is absent. Upon adding density interactions between the fermions, we identify an exact mapping to an XXZ spin chain in a random binary magnetic field, thereby establishing the existence of many-body localization with its logarithmic entanglement growth in a fully disorder-free system.

5.
Phys Rev Lett ; 118(26): 266601, 2017 Jun 30.
Article in English | MEDLINE | ID: mdl-28707931

ABSTRACT

The venerable phenomena of Anderson localization, along with the much more recent many-body localization, both depend crucially on the presence of disorder. The latter enters either in the form of quenched disorder in the parameters of the Hamiltonian, or through a special choice of a disordered initial state. Here, we present a model with localization arising in a very simple, completely translationally invariant quantum model, with only local interactions between spins and fermions. By identifying an extensive set of conserved quantities, we show that the system generates purely dynamically its own disorder, which gives rise to localization of fermionic degrees of freedom. Our work gives an answer to a decades old question whether quenched disorder is a necessary condition for localization. It also offers new insights into the physics of many-body localization, lattice gauge theories, and quantum disentangled liquids.

6.
Nat Mater ; 15(7): 733-40, 2016 07.
Article in English | MEDLINE | ID: mdl-27043779

ABSTRACT

Quantum spin liquids (QSLs) are topological states of matter exhibiting remarkable properties such as the capacity to protect quantum information from decoherence. Whereas their featureless ground states have precluded their straightforward experimental identification, excited states are more revealing and particularly interesting owing to the emergence of fundamentally new excitations such as Majorana fermions. Ideal probes of these excitations are inelastic neutron scattering experiments. These we report here for a ruthenium-based material, α-RuCl3, continuing a major search (so far concentrated on iridium materials) for realizations of the celebrated Kitaev honeycomb topological QSL. Our measurements confirm the requisite strong spin-orbit coupling and low-temperature magnetic order matching predictions proximate to the QSL. We find stacking faults, inherent to the highly two-dimensional nature of the material, resolve an outstanding puzzle. Crucially, dynamical response measurements above interlayer energy scales are naturally accounted for in terms of deconfinement physics expected for QSLs. Comparing these with recent dynamical calculations involving gauge flux excitations and Majorana fermions of the pure Kitaev model, we propose the excitation spectrum of α-RuCl3 as a prime candidate for fractionalized Kitaev physics.


Subject(s)
Magnetic Fields , Magnets , Models, Chemical , Quantum Theory , Solutions/chemistry , Spin Labels , Cold Temperature , Computer Simulation , Radiation Dosage
7.
Phys Rev Lett ; 113(18): 187201, 2014 Oct 31.
Article in English | MEDLINE | ID: mdl-25396391

ABSTRACT

We show how Raman spectroscopy can serve as a valuable tool for diagnosing quantum spin liquids (QSL). We find that the Raman response of the gapless QSL of the Kitaev-Heisenberg model exhibits signatures of spin fractionalization into Majorana fermions, which give rise to a broad signal reflecting their density of states, and Z(2) gauge fluxes, which also contribute a sharp feature. We discuss the current experimental situation and explore more generally the effect of breaking the integrability on response functions of Kitaev spin liquids.

9.
Phys Rev Lett ; 107(17): 177003, 2011 Oct 21.
Article in English | MEDLINE | ID: mdl-22107566

ABSTRACT

We report inelastic neutron scattering measurements of the resonant spin excitations in Ba(1-x)K(x)Fe(2)As(2) over a broad range of electron band filling. The fall in the superconducting transition temperature with hole doping coincides with the magnetic excitations splitting into two incommensurate peaks because of the growing mismatch in the hole and electron Fermi surface volumes, as confirmed by a tight-binding model with s(±)-symmetry pairing. The reduction in Fermi surface nesting is accompanied by a collapse of the resonance binding energy and its spectral weight, caused by the weakening of electron-electron correlations.

10.
Dermatology ; 222(2): 113-8, 2011.
Article in English | MEDLINE | ID: mdl-21464557

ABSTRACT

Eosinophilic ulcer of the oral mucosa is a benign lesion of unclear pathogenesis mostly affecting the tongue. It has been suggested to represent a reactive pattern to several stimuli. We report on a 12-year-old boy who presented with a painless infiltrating ulcer on the gingiva of the lower jaw, which was covered by necrotic yellowish slough. There were no pathologic features of the jawbones or regional lymph nodes. Histopathological, immunohistochemical and gene rearrangement studies were in agreement with eosinophilic ulcer with predominant oligoclonal CD3+ and CD30+ T lymphocytes expressing the Epstein-Barr virus membrane protein. The ulcer resolved within 4 weeks and follow-up for 3 years revealed no evidence of recurrence. Epstein-Barr virus may have played a role in triggering this reactive lymphoproliferative disorder.


Subject(s)
Eosinophilia/virology , Eosinophilic Granuloma/virology , Epstein-Barr Virus Infections/virology , Gingival Diseases/virology , Ki-1 Antigen/immunology , Lymphoproliferative Disorders/virology , Oral Ulcer/virology , Anti-Bacterial Agents/therapeutic use , CD3 Complex/immunology , Child , Eosinophilia/drug therapy , Eosinophilia/immunology , Eosinophilia/pathology , Eosinophilic Granuloma/drug therapy , Eosinophilic Granuloma/immunology , Eosinophilic Granuloma/pathology , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/pathology , Gingival Diseases/drug therapy , Gingival Diseases/immunology , Gingival Diseases/pathology , Humans , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/pathology , Male , Mouthwashes/therapeutic use , Oral Ulcer/drug therapy , Oral Ulcer/immunology , Oral Ulcer/pathology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Treatment Outcome
11.
Phys Rev Lett ; 104(25): 257001, 2010 Jun 25.
Article in English | MEDLINE | ID: mdl-20867410

ABSTRACT

We propose an explanation for the electronic nematic state observed recently in parent iron-based superconductors [T.-M. Chuang, Science 327, 181 (2010)10.1126/science.1181083]. We argue that the quasi-one-dimensional nanostructure identified in the quasiparticle interference (QPI) is a consequence of the interplay of the magnetic (π, 0) spin-density wave (SDW) order with the underlying electronic structure. We show that the evolution of the QPI peaks largely reflects quasiparticle scattering between bands involved in the SDW formation. Because of the ellipticity of the electron pocket and the fact that only one of the electron pockets is involved in the SDW, the resulting QPI has a pronounced one-dimensional structure. We further predict that the QPI crosses over to two dimensionality on an energy scale, set by the SDW gap.

12.
Eur Respir J ; 32(3): 807-11, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18757705

ABSTRACT

There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure. A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient's serum. The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient's work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 microg x m(-3) in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 microg x m(-3)). The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.


Subject(s)
Alveolitis, Extrinsic Allergic/etiology , Inhalation Exposure/adverse effects , Isocyanates/adverse effects , Occupational Exposure/adverse effects , Paint/adverse effects , Female , Humans , Middle Aged , Threshold Limit Values
13.
Pneumologie ; 60(12): 743-8, 2006 Dec.
Article in German | MEDLINE | ID: mdl-17163315

ABSTRACT

Multiple myeloma is a low malignant, non-Hodgkin's lymphoma, which is characterised by infiltration of the bone marrow by clonal prolifaration of atypical plasma cells. Clinical presentation is mostly determined by the sequeles of displacement of normal hemopoiesis, destruction of bones and the immune deficiency. Extramedullary manifestations are relatively rare. Pulmonary and pleural involvement has been described in case reports only. We report on a 75-year-old male patient in whom an IgG-secreting multiple myeloma type lambda, stage III (according to Durie and Salmon) has been diagnosed. Chest X-ray and CT revealed a diffuse confluent nodular pattern in the lungs and a large left-sided pleural effusion. Histology and immunohistochemistry confirmed diffuse infiltration of the lungs as well as the pleura by dysmature plasma cells with deposition of lambda-light chains. Preliminary treatment with vincristine and prednisone followed by polychemotherapy according to the VAD scheme was performed, which led to resolution of the pleuropulmonary changes.


Subject(s)
Lung Neoplasms/diagnosis , Multiple Myeloma/diagnosis , Pleural Neoplasms/diagnosis , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Humans , Immunoglobulin G/metabolism , Immunoglobulin lambda-Chains/metabolism , Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Plasma Cells/pathology , Pleura/pathology , Pleural Effusion, Malignant/pathology , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Prednisone/administration & dosage , Vincristine/administration & dosage
14.
Internist (Berl) ; 47(9): 944-51, 2006 Sep.
Article in German | MEDLINE | ID: mdl-16819658

ABSTRACT

Diffuse pulmonary hemorrhage denotes a diffuse bleeding into the alveoli as a result of severe damage of the alveolocapillary membrane. Autoimmune diseases, toxic injury and hemodynamic changes are the most frequent causes. A 45 year old male patient presented with diffuse alveolar hemorrhage. An Immunoglobulin A (IgA) paraprotein secreting myeloma was found to be the underlying cause. Immunohistochemistry revealed dense pericapillary and perivascular deposits of IgA, indicating a paraprotein mediated damage of the alveolocapillary membrane. The predominantly vascular pattern of damage was regarded as the most likely cause of the pulmonary hypertension in this patient. The diffuse pulmonary bleeding stopped after initiation of treatment consisting of vincristine, adriamycine and dexamethasone.


Subject(s)
Hemorrhage/etiology , Immunoglobulin A/blood , Immunoglobulin kappa-Chains/blood , Lung Diseases/etiology , Lung Neoplasms/diagnosis , Paraproteinemias/diagnosis , Plasmacytoma/diagnosis , Solitary Pulmonary Nodule/etiology , Blood Protein Electrophoresis , Diagnosis, Differential , Electrocardiography , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/pathology , Hemorrhage/blood , Hemorrhage/pathology , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/pathology , Immunoelectrophoresis , Kidney Glomerulus/pathology , Lung Diseases/blood , Lung Diseases/pathology , Lung Neoplasms/blood , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , Middle Aged , Paraproteinemias/blood , Paraproteinemias/complications , Paraproteinemias/pathology , Plasmacytoma/blood , Plasmacytoma/complications , Plasmacytoma/pathology , Pulmonary Alveoli/pathology , Tomography, X-Ray Computed
15.
Pneumologie ; 60(6): 347-54, 2006 Jun.
Article in German | MEDLINE | ID: mdl-16761229

ABSTRACT

Diffuse alveolar haemorrhage (DAH) denotes a diffuse intra-alveolar bleeding from small vessels as a result of severe damage of the alveolocapillary membrane of the lungs. These are comparatively rare, but than often life threatening events. The differential diagnosis is broad and comprises immunologic as well as toxic, infectious, hemodynamic, neoplastic and physical causes. DAH may be a manifestation of systemic diseases, as well as a result of an injury restricted to the lungs. The most frequent systemic diseases, that cause DAH are the so-called small vessel vasculititis-microscopic polyangiitis and Wegener's granulomatosis. More rarely Goodpasture's syndrome and systemic lupus erythematosus are causal. Alongside the immunologic processes mainly diseases with increased left-ventricular preload, infections and side effects of drugs have to be kept in mind. This review summarizes the differential diagnostic spectrum and the diagnostic workup of patients with DAH. Because early aggressive treatment can be life-saving, early and aimed diagnostics is essential.


Subject(s)
Hemorrhage/diagnosis , Lung Diseases/diagnosis , Anti-Glomerular Basement Membrane Disease/diagnosis , Diagnosis, Differential , Granulomatosis with Polyangiitis/diagnosis , Humans , Lupus Erythematosus, Systemic/diagnosis , Pulmonary Alveoli/pathology , Radiography, Thoracic
16.
Pneumologie ; 59(7): 456-60, 2005 Jul.
Article in German | MEDLINE | ID: mdl-16047279

ABSTRACT

Primary pulmonary rhabdomyosarcoma is a rare entity and the histological differential diagnosis can be difficult. We report on a 43-year old female patient, smoker (25 pack-years), in whom a large solitary brain metastasis was diagnosed and enucleated. Histological examination revealed a typical small cell carcinoma and histological examination of biopsies obtained from a tumor in the left upper lobe of the lung was compatible with a small cell carcinoma. Despite chemotherapy there was a progressive tumor growth. Bronchial biopsies again showed a small cell tumor, although immunohistochemistry proved it to be a pleomorphic rhabdomyosarcoma. Due to the progressive tumor growth with necrosis and superinfection and a lack of further metastases lobectomy of the left upper lobe was performed, complicated by postoperative pleural empyema, limiting the possibilities of adjuvant therapy. Early relapse occurred with pleural, pulmonary, chest wall and spinal metastases. Laminectomy and extirpation of the spinal metastases, local radiotherapy and chemotherapy with iphosphamide and doxorubicine led to partial remission and clinical improvement for few months only. The patient died from metastatic primary rhabdomyosarcoma of the lung. This rare tumor mimicked small cell lung cancer. Appraisal of the atypical clinical course and a close dialogue between pathologists and clinicians enabled the correct diagnosis.


Subject(s)
Carcinoma, Small Cell/pathology , Lung Neoplasms/pathology , Rhabdomyosarcoma/pathology , Adult , Carcinoma, Small Cell/surgery , Combined Modality Therapy , Diagnosis, Differential , Fatal Outcome , Female , Humans , Lung Neoplasms/surgery , Recurrence , Rhabdomyosarcoma/surgery
17.
Respiration ; 70(2): 161-5, 2003.
Article in English | MEDLINE | ID: mdl-12740513

ABSTRACT

BACKGROUND: Hypercoagulability is common even after minimally invasive surgical techniques and is pathogenetically linked to postoperative thrombotic and cardiac complications. The activation of the coagulation and fibrinolytic systems after bronchoscopic and thoracoscopic investigations has not yet been elucidated. OBJECTIVE: The aim of our study was to evaluate whether bronchoscopic and thoracoscopic investigations activate the fibrinolytic system. METHODS: This study assessed cross-linked fibrinogen degradation products (D-dimer) in 120 patients after bronchoscopy with and without biopsies and/or bronchoalveolar lavage and after thoracoscopy with biopsies of the parietal pleura. RESULTS: Both bronchoscopy and thoracoscopy induced a minor but significant increase in D-dimers in most patients, reversible mostly within 24 h. In rare cases, distinct increases lasting at least 24 h occurred. CONCLUSIONS: The slight and temporary increase in serum D-dimers induced by bronchoscopy and thoracoscopy is nonsignificant in most patients; however, in some cases, the coagulation/fibrinolytic systems may become markedly activated.


Subject(s)
Antifibrinolytic Agents/analysis , Biomarkers/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis/physiology , Bronchoscopy , Female , Humans , Male , Thoracoscopy
18.
J Cardiovasc Surg (Torino) ; 42(4): 555-60, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11455296

ABSTRACT

BACKGROUND: The aim of our study was to examine the significance of tumour DNA-content and proliferation in lung cancer. METHODS: The DNA content and S-phase fraction (SPF) was determined by flow cytometry in 125 resected tumours of patients with non-small cell lung cancer. In 40 cases we compared the SPF with immunohistochemical staining of the Ki-67 protein using MIB-1 antibody. RESULTS: DNA aneuploidy was detected in 84.8% (106/125). Cell cycle analysis for the determination of proliferation activity was only possible in 69 (55.2%) cases. An SPF of 0-8% as a sign of low proliferation was found in 27 specimens. In advanced tumours at stage III and IV the proportion of tumours with SPF 9-16% was significantly (p<0.05) increased as compared to tumours at stage I and II. There was a significant correlation (p=0.012, ascent: 0.045) between SPF and MIB-1. Patients with aneuploid tumours had a relative risk of 1.4 to die earlier than patients with diploid tumours. Patients with SPF of 9-16% in the tumour tended to decreased survival (5-year survival rate: 29%) in correlation to patients with a percentage of SPF 0-8% (5-year survival rate: 38%, p=0.5). These differences were significant (p=0.048) in patients with adenocarcinomas only. In the multivariate COX-regression model age (p=0.03) and stage (p=0.0001) were significant prognostic factors, ploidy state (p=0.33) was of no prognostic significance. CONCLUSIONS: Flow cytometry seems to be a useful method for understanding the clinical behaviour of lung cancer. Especially the SPF in adenocarcinomas may be used as a prognostic indicator.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA, Neoplasm/analysis , Ki-67 Antigen/analysis , Lung Neoplasms/genetics , Analysis of Variance , Aneuploidy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle , Flow Cytometry , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Middle Aged , Survival Rate
19.
Bioorg Med Chem Lett ; 11(15): 2011-5, 2001 Aug 06.
Article in English | MEDLINE | ID: mdl-11454469

ABSTRACT

A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta-amino acids were explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.


Subject(s)
Osteoporosis/prevention & control , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Receptors, Vitronectin/antagonists & inhibitors , Animals , Binding Sites/drug effects , Binding Sites/physiology , Carbamates/chemistry , Cell Adhesion/drug effects , Cell Adhesion/physiology , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Guanidine/chemistry , Parathyroidectomy , Platelet Glycoprotein GPIIb-IIIa Complex/chemistry , Rats , Receptors, Vitronectin/metabolism , Sensitivity and Specificity , Sulfonamides/chemistry , Thiophenes/chemical synthesis , Thiophenes/pharmacology , Thyroidectomy
20.
Circulation ; 103(8): 1135-41, 2001 Feb 27.
Article in English | MEDLINE | ID: mdl-11222478

ABSTRACT

BACKGROUND: Thrombosis and neointima formation limit the efficacy of coronary angioplasty (PTCA). Clinical trials have implicated the adhesion molecules integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) in these processes. The roles of these molecules in vascular smooth muscle cell adhesion, platelet aggregation, and the thrombotic and neointimal response to oversize porcine PTCA was investigated by use of a selective alpha(IIb)beta(3) antagonist (lamifiban), a selective alpha(v)beta(3) antagonist (VO514), and a combined alpha(IIb)beta(3)/alpha(v)beta(3) antagonist (G3580). METHODS AND RESULTS: In vitro, both alpha(v)beta(3) inhibitors caused dose-dependent inhibition of porcine vascular smooth muscle cell adhesion to vitronectin but not to collagen type IV, fibronectin, or laminin, whereas selective alpha(IIb)beta(3) inhibition had no effect. Intravenous infusions of either alpha(IIb)beta(3) inhibitor in swine profoundly inhibited ex vivo platelet aggregation to ADP, whereas selective alpha(v)beta(3) inhibition had no effect. In a porcine PTCA model, intravenous infusions of the integrin antagonists were administered for 14 days after oversized balloon angioplasty injury. After PTCA, there was regional upregulation of integrin alpha(v)beta(3) in the developing neointima, as assessed by immunohistochemistry. Six hours after PTCA, obstruction of lumen by thrombus was reduced significantly by alpha(IIb)beta(3) inhibition compared with either control or alpha(v)beta(3) inhibition (mean control, 18.7%; VO514, 18.5%; lamifiban, 6.4%; G3580, 7.9%). Twenty-eight days after PTCA, there was a significant reduction of neointima with inhibitors of either integrin (mean intima/media ratio: control, 3.08; VO514, 1.33; lamifiban, 0.97; G3580, 1.32). CONCLUSIONS: We conclude that both integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) participate in neointima development after experimental angioplasty.


Subject(s)
Acetates/therapeutic use , Thrombosis/prevention & control , Tyrosine/analogs & derivatives , Tyrosine/therapeutic use , Acetates/pharmacology , Angioplasty, Balloon, Coronary/adverse effects , Animals , Cell Adhesion/drug effects , Disease Models, Animal , Immunohistochemistry , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Platelet Glycoprotein GPIIb-IIIa Complex/biosynthesis , Receptors, Vitronectin/antagonists & inhibitors , Receptors, Vitronectin/biosynthesis , Swine , Thrombosis/etiology , Tunica Intima/drug effects , Tyrosine/pharmacology
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