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  1. Article ; Online: Physical activity and quality of life in patients with pulmonary hypertension.

    Cascino, Thomas M / McLaughlin, Vallerie V / Richardson, Caroline R / Behbahani-Nejad, Nilofar / Moles, Victor M / Visovatti, Scott H / Jackson, Elizabeth A

    The European respiratory journal

    2019  Volume 53, Issue 6

    MeSH term(s) Aged ; Exercise ; Exercise Therapy ; Female ; Humans ; Hypertension, Pulmonary/therapy ; Linear Models ; Male ; Middle Aged ; Prospective Studies ; Quality of Life ; Walk Test
    Language English
    Publishing date 2019-06-20
    Publishing country England
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.00028-2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Barriers to physical activity in patients with pulmonary hypertension.

    Cascino, Thomas M / McLaughlin, Vallerie V / Richardson, Caroline R / Behbahani-Nejad, Nilofar / Moles, Victor M / Visovatti, Scott H / Jackson, Elizabeth A

    Pulmonary circulation

    2018  Volume 9, Issue 2, Page(s) 2045894019847895

    Abstract: Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have low levels of physical activity (PA). Increased PA has health benefits including improved quality of life. This study aimed to identify ... ...

    Abstract Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have low levels of physical activity (PA). Increased PA has health benefits including improved quality of life. This study aimed to identify patient-perceived barriers to PA that correlate with objectively measured PA in this population. We performed a cross-sectional survey of 40 patients with PAH and CTEPH. Participants rated how often 15 barriers interfere with being physically active on a 5-point Likert Scale. The primary outcome measure was PA quantified using the Fitbit Zip activity tracker for two weeks. The primary independent variables were the 15 barriers and a summary score (total average barriers). Separate multivariable linear regressions were performed to assess the association between the 15 barriers and the summary score and PA adjusting for age, sex, and PAH etiology. Of the participants, 85% (34/40) had valid step counts and were included. Of these 34, 85% (n = 29) were female and 91% (n = 31) had PAH. The median (interquartile range [IQR]) number of daily steps was 3913 (2309-6313). The barriers endorsed most strongly were lack of self-discipline, lack of energy, and lack of interest. In the multivariable analysis, a 1-unit increase in perceived lack of interest, lack of enjoyment, and lack of skills was associated with a significant decrease in step counts of -1414 steps (95% confidence interval [CI] = (-2580 - -248), -1458 steps (-2404 - -511), and -1533 steps (-2910 - -156), respectively. Counseling and interventions aimed at increasing PA in patients with PAH should address interest, enjoyment, and skill development.
    Language English
    Publishing date 2018-11-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2638089-4
    ISSN 2045-8940 ; 2045-8932
    ISSN (online) 2045-8940
    ISSN 2045-8932
    DOI 10.1177/2045894019847895
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast like Synoviocytes.

    Morgan, Rachel L / Behbahani-Nejad, Nilofar / Endres, Judith / Amin, M Asif / Lepore, Nick J / Du, Yuxuan / Urquhart, Andrew / Chung, Kevin C / Fox, David A

    PloS one

    2016  Volume 11, Issue 9, Page(s) e0162008

    Abstract: Aminopeptidase N/CD13 is highly expressed by fibroblast like synoviocytes (FLS) and may play a role in rheumatoid arthritis (RA). CD13 was previously detected in human synovial fluid where it was significantly increased in RA compared to osteoarthritis. ... ...

    Abstract Aminopeptidase N/CD13 is highly expressed by fibroblast like synoviocytes (FLS) and may play a role in rheumatoid arthritis (RA). CD13 was previously detected in human synovial fluid where it was significantly increased in RA compared to osteoarthritis. In this study we found that CD13 in biological fluids (plasma, synovial fluid, FLS culture supernatant) is present as both a soluble molecule and on extracellular vesicles, including exosomes, as assessed by differential ultracentrifugation and density gradient separation. Having determined CD13 could be released as a soluble molecule from FLS, we examined potential mechanisms by which CD13 might be shed from the FLS membrane. The use of protease inhibitors revealed that CD13 is cleaved from the FLS surface by metalloproteinases. siRNA treatment of FLS revealed one of those proteases to be MMP14. We determined that pro-inflammatory cytokines (TNFα, IFNγ, IL-17) upregulated CD13 mRNA in FLS, which may contribute to the increased CD13 in RA synovium and synovial fluid. Inhibition of CD13 function by either inhibitors of enzymatic activity or anti-CD13 antibodies resulted in decreased growth and diminished migration of FLS. This suggests that CD13 may be involved in the pathogenic hyperplasia of RA FLS. This data expands potential roles for CD13 in the pathogenesis of RA.
    Language English
    Publishing date 2016-09-22
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0162008
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  4. Article ; Online: Fresh versus frozen engineered bone-ligament-bone grafts for sheep anterior cruciate ligament repair.

    Mahalingam, Vasudevan D / Behbahani-Nejad, Nilofar / Ronan, Elizabeth A / Olsen, Tyler J / Smietana, Michael J / Wojtys, Edward M / Wellik, Deneen M / Arruda, Ellen M / Larkin, Lisa M

    Tissue engineering. Part C, Methods

    2015  Volume 21, Issue 6, Page(s) 548–556

    Abstract: Surgical intervention is often required to restore knee instability in patients with anterior cruciate ligament (ACL) injury. The most commonly used grafts for ACL reconstruction are tendon autografts or allografts. These current options, however, have ... ...

    Abstract Surgical intervention is often required to restore knee instability in patients with anterior cruciate ligament (ACL) injury. The most commonly used grafts for ACL reconstruction are tendon autografts or allografts. These current options, however, have shown failure rates requiring revision and continued instability in the long term. The mismatched biomechanical properties of the current tendon grafts compared with native ACL tissue are thought to contribute to these poor outcomes and potential risk of early onset osteoarthritis. As a possible solution to these issues, our laboratory has fabricated tissue-engineered ligament constructs that exhibit structural and functional properties similar to those of native ACL tissue after 6 months implantation. In addition, these tissue-engineered grafts achieve vascular and neural development that exceeds those of patellar tendon grafts. However, the utility of our tissue-engineered grafts is limited by the labor-intensive method required to produce the constructs and the need to use the constructs fresh, directly from the cell culturing system. Ideally, these constructs would be fabricated and stored until needed. Thus, in this study, we investigated the efficacy of freezing our tissue-engineered constructs as a method of preservation before use for ACL reconstruction. We hypothesized that frozen constructs would have similar histological and biomechanical outcomes compared with our fresh model. Our results showed that 6 months postimplantation as an ACL replacement graft, both our tissue-engineered fresh and frozen grafts demonstrated similar mechanical and histological outcomes, indicating that freezing is a suitable method for preserving and storing our graft before ACL reconstruction. The ability to use frozen constructs significantly increases the versatility of our graft technology expanding the clinical utility of our graft.
    MeSH term(s) Animals ; Anterior Cruciate Ligament/metabolism ; Anterior Cruciate Ligament/transplantation ; Bone Transplantation ; Freezing ; Graft Survival ; Preservation, Biological/methods ; Sheep ; Time Factors ; Tissue Engineering/methods
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420585-0
    ISSN 1937-3392 ; 1937-3384
    ISSN (online) 1937-3392
    ISSN 1937-3384
    DOI 10.1089/ten.TEC.2014.0542
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  5. Article ; Online: Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

    Mahalingam, Vasudevan D / Behbahani-Nejad, Nilofar / Horine, Storm V / Olsen, Tyler J / Smietana, Michael J / Wojtys, Edward M / Wellik, Deneen M / Arruda, Ellen M / Larkin, Lisa M

    Tissue engineering. Part A

    2015  Volume 21, Issue 5-6, Page(s) 1047–1054

    Abstract: The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made ...

    Abstract The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.
    MeSH term(s) Animals ; Anterior Cruciate Ligament/surgery ; Anterior Cruciate Ligament Reconstruction ; Bone Transplantation ; Bone and Bones/blood supply ; Bone and Bones/innervation ; Collagen/metabolism ; Elastic Modulus ; Elastin/metabolism ; Joint Instability ; Knee Joint/pathology ; Knee Joint/physiopathology ; Ligaments/blood supply ; Ligaments/innervation ; Ligaments/transplantation ; Neovascularization, Physiologic ; Sheep ; Tissue Engineering/methods ; Transplantation, Autologous ; Transplantation, Homologous
    Chemical Substances Collagen (9007-34-5) ; Elastin (9007-58-3)
    Language English
    Publishing date 2015-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.TEA.2014.0422
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  6. Article ; Online: Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes in rheumatoid arthritis: role of CD13 in chemotaxis of cytokine-activated T cells independent of enzymatic activity.

    Morgan, Rachel / Endres, Judith / Behbahani-Nejad, Nilofar / Phillips, Kristine / Ruth, Jeffrey H / Friday, Sean C / Edhayan, Gautam / Lanigan, Thomas / Urquhart, Andrew / Chung, Kevin C / Fox, David A

    Arthritis & rheumatology (Hoboken, N.J.)

    2014  Volume 67, Issue 1, Page(s) 74–85

    Abstract: Objective: Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure ... ...

    Abstract Objective: Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure CD13 in vivo and in vitro in RA samples and to determine whether CD13 could play a role in the homing of T cells to the RA joint.
    Methods: Interleukin-17-treated FLS were used to immunize mice, from which a novel anti-human CD13 monoclonal antibody (mAb), 591.1D7.34, was developed. The mAb 591.1D7.34 and a second anti-CD13 mAb, WM15, were used to develop a novel enzyme-linked immunosorbent assay (ELISA) for CD13, and CD13 enzymatic activity was measured in parallel. Chemotaxis of cytokine-activated T cells was measured by a chemotaxis-under-agarose assay.
    Results: We detected substantial amounts of CD13 in synovial fluid (SF), sera, FLS lysates, and culture supernatants by ELISA, with a significant increase in CD13 in RA SF when compared to osteoarthritis SF. CD13 accounted for most but not all of the CD13-like enzymatic activity in SF. Recombinant human CD13 was chemotactic for cytokine-activated T cells through a G protein-coupled receptor and contributed to the chemotactic properties of SF independently of enzymatic activity.
    Conclusion: CD13 is released from FLS into culture supernatants and is found in SF. CD13 induces chemotaxis of cytokine-activated T cells, a T cell population similar to that found in RA synovium. These data suggest that CD13 could play an important role as a T cell chemoattractant, in a positive feedback loop that contributes to RA synovitis.
    MeSH term(s) Antibodies, Anti-Idiotypic/pharmacology ; Antibodies, Monoclonal/pharmacology ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/physiopathology ; CD13 Antigens/metabolism ; Cell Movement/drug effects ; Cell Movement/physiology ; Cells, Cultured ; Chemotaxis/drug effects ; Chemotaxis/physiology ; Cytokines/metabolism ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Humans ; Interleukin-17/pharmacology ; Osteoarthritis/metabolism ; Osteoarthritis/pathology ; Osteoarthritis/physiopathology ; Receptors, G-Protein-Coupled/metabolism ; Recombinant Proteins/pharmacology ; Synovial Membrane/drug effects ; Synovial Membrane/metabolism ; Synovial Membrane/pathology ; T-Lymphocytes/pathology
    Chemical Substances Antibodies, Anti-Idiotypic ; Antibodies, Monoclonal ; Cytokines ; Interleukin-17 ; Receptors, G-Protein-Coupled ; Recombinant Proteins ; CD13 Antigens (EC 3.4.11.2)
    Language English
    Publishing date 2014-09-11
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.38878
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