L. Puttagunta | University of Alberta (original) (raw)

Papers by L. Puttagunta

AJP Lung Cellular and Molecular Physiology

ABSTRACT

Laboratory Investigation, 1992

The Journal of Heart and Lung Transplantation

The Journal of Heart and Lung Transplantation, 2010

Canadian Association of Radiologists Journal, 1999

Allergy

Proteinase‐Activated Receptor‐2 (PAR2) is a G protein‐coupled receptor activated by serine protei... more Proteinase‐Activated Receptor‐2 (PAR2) is a G protein‐coupled receptor activated by serine proteinases. We have shown that PAR2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesized that functional inhibition of PAR2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models.

Clinical & Experimental Allergy, 2015

Proteinase-Activated Receptor 2 (PAR2 ) is a G protein-coupled receptor activated by trypsin-like... more Proteinase-Activated Receptor 2 (PAR2 ) is a G protein-coupled receptor activated by trypsin-like serine proteinases. PAR2 activation has been associated with inflammation including allergic airway inflammation. We have also shown that PAR2 activation in the airways leads to allergic sensitization. The exact contribution of PAR2 in the development of eosinophilic inflammation and airway hyperresponsiveness (AHR) in sensitized individuals is not clear. To investigate whether functional inhibition of PAR2 during allergen challenge of allergic mice would inhibit allergen-induced AHR and inflammation in mouse models of asthma. Mice were sensitized and challenged with ovalbumin (OVA) or cockroach extract (CE). To investigate the role of PAR2 in the development of AHR and airway inflammation we administered blocking anti-PAR2 antibodies, or a cell permeable peptide inhibitor of PAR2 signaling, pepducin, i.n. before allergen challenges and then assessed AHR and airway inflammation. Administration of anti-PAR2 antibodies significantly inhibited OVA- and CE-induced AHR and airway inflammation. In particular two anti-PAR2 antibodies, the monoclonal SAM-11 and polyclonal B5, inhibited AHR, airway eosinophilia, the increase of cytokines in the lung tissue and antigen-specific T cell proliferation, but had no effect on antigen-specific IgG and IgE levels. Pepducin was also effective in inhibiting AHR and airway inflammation in an OVA model of allergic airway inflammation. Functional blockade of PAR2 in the airways during allergen challenge improves allergen-induced AHR and inflammation in mice. Therefore, topical PAR2 blockade in the airways, through anti- PAR2 antibodies or molecules that interrupt PAR2 signaling, has the potential to be used as a therapeutic option in allergic asthma. This article is protected by copyright. All rights reserved.

The International Journal of Tuberculosis and Lung Disease, 2010

Bronchial anthracofibrosis is a condition of proximal airway narrowing or obliteration and hyperp... more Bronchial anthracofibrosis is a condition of proximal airway narrowing or obliteration and hyperpigmentation in persons with or without a history of occupational dust exposure. It is a bronchoscopic finding that is not uncommonly associated with pulmonary tuberculosis (PTB) in residents of South Korea, Iran and India. It is largely unrecognized in the Western world. We report the frequency of anthracofibrosis in foreign-born PTB patients who underwent bronchoscopy in two cities of Canada. We describe the composition of the pigment in the lungs of patients and speculate on the pathogenesis of anthracofibrosis-associated PTB. Anthracofibrosis was present in 10/60 (16.7%) foreign-born patients who underwent bronchoscopy and had PTB between 2002 and 2006. Compared to patients from other Asian countries, patients from the Indian subcontinent were more likely to have anthracofibrosis (9/18, 50.0% vs. 1/26, 3.7%, P < 0.001). Carbonaceous particles, silica and silicates predominated in t...

Advances in Experimental Medicine and Biology, 2001

ABSTRACT Chronic Hypoxic Pulmonary Hypertension (CH-PHT) is characterized by pulmonary artery (PA... more ABSTRACT Chronic Hypoxic Pulmonary Hypertension (CH-PHT) is characterized by pulmonary artery (PA) vasoconstriction and cell proliferation/hypertrophy. PA smooth muscle cell (PASMC) contractility and proliferation are controlled by cytosolic Ca++ levels, which are largely determined by membrane potential (E(M)). E(M) is depolarized in CH-PHT due to decreased expression and functional inhibition of several redox-regulated, 4-aminopyridine (4-AP) sensitive, voltage-gated K+ channels (Kv1.5 and Kv2.1). Humans with Pulmonary Arterial Hypertension (PAH) also have decreased PASMC expression of Kv1.5 and Kv2.1. We speculate this "K+-channelopathy" contributes to PASMC depolarization and Ca++ overload thus promoting vasoconstriction and PASMC proliferation. We hypothesized that restoration of Kv channel expression in PHT and might eventually be beneficial. Two strategies were used to increase Kv channel expression in PASMCs: oral administration of a metabolic modulator drug (Dichloroacetate, DCA) and direct Kv gene transfer using an adenovirus (Ad5-Kv2.1). DCA a pyruvate dehydrogenase kinase inhibitor, promotes a more oxidized redox state mimicking normoxia and previously has been noted to increase K+ current in myocytes. Rats were given DCA in the drinking water after the development of CH-PHT and hemodynamics were measured approximately 5 days later. We also tested the ability of Ad5-Kv2.1 to increase Kv2.1 channel expression and function in human PAs ex vivo. The DCA-treated rats had decreased PVR, RVH and PA remodeling compared to the control CH-PHT rats (n=5/group, p<0.05). DCA restored Kv2.1 expression and PASMC Kv current density to near normoxic levels. Adenoviral gene transfer increased expression of Kv2.1 channels and enhanced 4-AP constriction in human PAs. Increasing Kv channel function in PAs is feasible and might be beneficial.

Canadian Association of Radiologists Journal

AJP: Lung Cellular and Molecular Physiology, 2009

integrative aspects of normal and abnormal function of cells and components of the respiratory sy... more integrative aspects of normal and abnormal function of cells and components of the respiratory system. It is published 12 times a publishes original research covering the broad scope of molecular, cellular, and AJP -Lung Cellular and Molecular Physiology on Acute lung injury (ALI) is an inflammatory disorder associated with recruitment and activation of neutrophils in lungs. Rac2, a member of the Rho GTPase subfamily, is an essential regulator of neutrophil degranulation, superoxide release, and chemotaxis. Here, we hypothesized that Rac2 is important in mediating lung injury. Using a model of IgG immune complexmediated ALI, we showed that injury was attenuated in rac2 Ϫ/Ϫ mice compared with wild-type (WT) mice undergoing ALI, with significant decreases in alveolar leukocyte numbers, vascular leakage, and the inflammatory mediators, myeloperoxidase (MPO) and matrix metalloproteinases (MMPs). Reduced injury in rac2 Ϫ/Ϫ mice was not associated with diminished cytokine and chemokine production, since bronchoalveolar lavage (BAL) levels of IL-17, TNF, CCL3, CXCL1, and CXCL2 were similarly increased in WT and rac2 Ϫ/Ϫ mice with ALI compared with sham-treated mice (no ALI). BAL levels of MMP-2 and MMP-9 were significantly decreased in the airways of rac2 Ϫ/Ϫ mice with ALI. Immunohistochemical analysis revealed that MMP-2 and MMP-9 expression was evident in alveolar macrophages and interstitial neutrophils in WT ALI. In contrast, MMP-positive cells were less prominent in rac2 Ϫ/Ϫ mice with ALI. Chimeric mice showed that Rac2-mediated lung injury was dependent on hematopoietic cells derived from bone marrow. We propose that lung injury in response to immune complex deposition is dependent on Rac2 in alveolar macrophages and neutrophils.

C65. DIFFUSE PARENCHYMAL LUNG DISEASES: BASIC AND CLINICAL STUDIES

International Journal of Radiation Oncology*Biology*Physics

Background: Auramine-Rhodamine (AR) positive (+) staining of tissue samples can be very helpful f... more Background: Auramine-Rhodamine (AR) positive (+) staining of tissue samples can be very helpful for the diagnosis of tuberculosis (TB). However, with new liquid culture methods, the expectation is that a smear (+) specimen should grow a mycobacterium. The objective of this study was to compare the culture results and histology of AR (+) tissue specimens. Methods: Tissue samples collected from patients that were submitted for mycobacterial culture and had AR (+) staining were retrospectively analyzed with respect to mycobacterial culture result, histology and/or Ziehl-Neelsen (ZN) method. Results: Of 54 AR (+) specimens 17 samples revealed a (+) culture result for M. tuberculosis (MTB), 6 were (+) for M. avium complex (MAC), 2 were (+) for M.gordonae, 1 specimen was (+) for MTB and MAC, and 28 specimens were culture negative (-). Necrotizing granulomas were present in 38 of the samples (14 grew mycobacteria), 14 specimens contained non-necrotizing granulomas (1 grew mycobacteria) and...

The Journal of otolaryngology, 2001

Historically, squamous cells exfoliated from head and neck carcinoma resection have been implicat... more Historically, squamous cells exfoliated from head and neck carcinoma resection have been implicated in locoregional recurrence, but there have been few studies demonstrating the presence of these cells. This study was designed to evaluate the presence of exfoliated malignant cells in surgical irrigation fluid collected during head and neck cancer resection. Thirty patients undergoing surgery for biopsy-proven squamous cell carcinoma had their surgical sites irrigated with 1,000 cc of normal saline. Surgical gloves and instruments were also washed. These samples were prepared and stained using standard squamous cell cytologic stains. All cases were reviewed by one cytopathologist. Eighteen patients (60%) had positive or suspicious cytology detected in at least one of the surgical samples. In patients with T0 and T1 tumours, all surgical samples were negative. Positive or suspicious cytology was detected in the primary site and glove and instrument irrigation in 40% of patients with T...

Canadian respiratory journal : journal of the Canadian Thoracic Society

The role and timing of surgical decortication in the management of a primary tuberculous pleural ... more The role and timing of surgical decortication in the management of a primary tuberculous pleural peel remains controversial. The present report describes the case of a young man with an extensive primary tuberculous pleural peel that responded dramatically to medical therapy. A serious attempt at surgical decortication three weeks into antituberculous drug therapy may have removed some compressive aspects of the peel, facilitating lung expansion. However, it had almost no measurable impact on the size of peel and was technically very difficult. Response to treatment was measured anatomically (computed tomography scans) and physiologically (pulmonary function tests).

AJR. American journal of roentgenology, 2000

Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes, 1999