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Papers by raj put verma
Periodontal diseases are complex, multifactorial, polymicrobial immunoinflammatory infections. A ... more Periodontal diseases are complex, multifactorial, polymicrobial immunoinflammatory infections. A prominent pathogenic consortium in subgingval biofilms in human periodontitis includes Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf). Objective: The study examined alveolar bone resorption induced by periodontal pathogens P. gingivalis, T. denticola, and T. forsythia in monomicrobial and mixed microbial periodontal disease in rats. Methods: Adult rats were infected with P. gingivalis and T. denticola as oral gavage. Oral infections were induced either as monobacterial (Pg, Td) or mixed microbial (Pg+Td). Rats were euthanized at 6 and 12 weeks following exposure to bacteria and subsequent induction of periodontal disease. The jaws were removed, autoclaved, defleshed, maxilla and mandibles separated, and alveolar bone loss was evaluated using radiography. Digital radiographs were acquired with orthogonal projection geometry using an exposure time of...
India Quarterly: A Journal of International Affairs, 2015
Jha, Prashant, Battles of the New Republic: A Contemporary History of Nepal (New Delhi: Aleph Boo... more Jha, Prashant, Battles of the New Republic: A Contemporary History of Nepal (New Delhi: Aleph Book Publication, 2014). Pp. 358, Price ₹ 395.
PLoS ONE, 2014
Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Tr... more Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virusderived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE 2/2 mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P,0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P,0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE 2/2 mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine proteases significantly reduced arterial plaque growth, suggesting a central role for chemokine-mediated inflammation after BA in P. gingivalis infected mice.
Scientific Reports, 2014
a1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this biological function was partl... more a1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this biological function was partly attributed a1(IV)NC1 binding to a1b1-integrin. However, its potent antiangiogenic activity and the molecular targets of a1(IV)NC1 has not been investigated. In the present study, the regulation of MMP-2 activation by a1(IV)NC1 was evaluated. a1b1-integrin which is required for inhibition of angiogenesis is not playing a role in cellular invasion and inhibition of MMP-2 activation by a1(IV)NC1. We found that a1(IV)NC1 binds the CBD of MMP-2 and forming a stable complex that prevents activation of MMP-2. The antiangiogenic activity of a1(IV)NC1 is mediated, in part, by this binding activity. In addition, up-regulation of TIMP-2 by a1(IV)NC1 led to saturation of MT1-MMP binding sites, which in turn led to inhibition of MMP-2 activation. In-vivo studies using a1-integrin null-mice treated with higher doses of a1(IV)NC1 showed integrin independent inhibition of tumor growth and active-MMP-2, without affecting MMP-9, MMP-7 and angiostatin. D uring vascular basement membranes (VBM) remodeling, crucial circulating angiogenic and antiangiogenic molecules are liberated that controls formation of new capillaries 1,2. Remodeling of basement membrane and de-novo expression of provisional matrix proteins promote cell adhesion, migration and differentiation that play important roles in angiogenesis 1,2. Angiogenesis is one of the most consistent host responses associated with cancer tumor angiogenesis which is partly regulated by endogenous angiogenesis inhibitors that are released from VBM upon proteolysis 3-9. The endogenous angiogenesis inhibitors released from VBM includes some of the type IV collagen derived non-collagenous domains (NC1) that are liberated from extracellular matrix (ECM) by matrix metalloproteinases (MMPs) 5,7,10-13. ECM degradation by MMPs is prerequisite during tumor growth and metastasis 14-18. MMPs exist as both soluble and membrane-anchored types (MT-MMPs) 19. Soluble MMPs are responsible for ECM degradation, whereas MT-MMPs participate in pericellular VBM degradation 20. The cell surface activation of proMMP-2 by MT1-MMP is pivotal in tumor invasion following degradation of VBM by MMP-2 21. The major component of vascular basement membrane (VBM) is type IV collagen. Type IV collagen have a1-a6 chains and have important roles in the assembly of BM 22,23. Remodeling of VBM can provide crucial angiogenic and anti-angiogenic molecules to control the formation of new capillaries 1,24,25. Such anti-angiogenic molecules of VBM include NC1 domain of a1-chains of type IV collagen 10,21,26-28. The C-terminal non-collagenous domain from a1-chain of type IV collagen, a1(IV)NC1 (arresten) is a 26-kDa protein induced by p53 that binds to a1b1-integrin and mediates its antiangiogenic actions and suppresses invasion of squamous cell carcinoma 10,21,26,29-31. a1(IV)NC1 and its N-and C-terminal domains are promoting apoptosis 27,32. In addition we also showed that a1(IV)NC1 inhibits MMP-2 activation without affecting expression 28. Despite its potent in-vitro and in-vivo antiangiogenic activity, the molecular targets of a1(IV)NC1 are yet to be identified. In the present study, we reported that a1(IV)NC1 inhibits invasion and MMP-2 activation by forming a complex with collagen binding domain (CBD) of MMP-2. These findings demonstrate that a1(IV)NC1 regulates MMP2 activation without affecting circulating MMP-9, 27 and angiostatin activation in-vitro and in-vivo. This regulation of MMP-2 activation contributes a1(IV)NC1 mediated regression of tumor angiogenesis in mice. These findings indicate that a novel MMP-2 regulatory mechanism of a1(IV)NC1 that partly regulate its anti-angiogenic and anti-tumorogenic activity.
PLoS ONE, 2013
Object: Antiangiogenic treatments are beginning to give promising outcomes in many vascular disea... more Object: Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and pro-apoptotic actions of a1(IV)NC1 and its N-and C-peptides a1S1(IV)NC1, a1S2(IV)NC1 were investigated in-vitro and in-vivo. Study Method: Endothelial cells (ECs) were treated with a1(IV)NC1, a1S1(IV)NC1, a1S2(IV)NC1 and in-vitro proliferation, migration, tube formation and apoptotic assays were executed. FasL, Fas, Caspase-8,-3 and PARP activations were studied using immunoblotting analysis using specific antibodies. Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using a1(IV)NC1 in a mice model. Results: Like a1(IV)NC1, its N-and C-terminal a1S2(IV)NC1 and a1S1(IV)NC1 domains posses anti-proliferative, proapoptotic activity and inhibit ECs migration and tube formation in-vitro. Both a1S1(IV)NC1 and a1S2(IV)NC1 domains promote apoptosis by activating FasL and down stream apoptotic events including activation of caspase-8,-3 and PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed apoptotic TUNEL positive microvasculature upon a1(IV)NC1 treatment, indicating inhibition of tumor angiogenesis and tumor growth. Further, the antitumor activity of a1(IV)NC1 was abrogated when caspase-3 inhibitor was used. These results conform additional properties of a1(IV)NC1 as an endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by activating FasL mediated caspase-3. Significance: a1(IV)NC1 and its N-and C-terminal a1S1(IV)NC1 and a1S2(IV)NC1 domains also posses pro-apoptotic and angioinhibitory activity in-vitro and in-vivo. a1(IV)NC1 regulates tumor angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These results demonstrate that a1(IV)NC1 and its peptides inhibit neo-vascular diseases.
The Indian journal of medical research, 2003
As isolation of Mycobacterium tuberculosis in culture requires a long time, there is a need for s... more As isolation of Mycobacterium tuberculosis in culture requires a long time, there is a need for simple rapid method for direct detection of M. tuberculosis from clinical specimens. Amplified nucleic acid hybridization assays such as polymerase chain reaction (PCR) have shown promising results. In the present study, the sensitivity of PCR assay was assessed over smear microscopy for rapid diagnosis of tuberculosis in pulmonary and extra-pulmonary samples from patients suspected to have tuberculosis. A total of 37 clinical samples from patients with pulmonary tuberculosis and 133 from patients with extra-pulmonary tuberculosis were subjected to Ziehl-Neelsen staining for smear preparation and PCR for detection of mycobacterial DNA. It was observed that 100 per cent of acid fast bacilli (AFB) positive and 35.7 per cent of AFB negative pulmonary samples and 82.76 per cent of AFB positive and 56.73 per cent of AFB negative extra-pulmonary samples were positive for mycobacterial DNA detec...
The Indian journal of medical research, 2011
Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are m... more Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are major cause of morbidity and mortality. The present study was carried out to assess the frequency of staphylococcal IVD associated infections in a paediatric ward of a tertiary case hospital. Prevalence of resistance to commonly used antimicrobials in hospital acquired staphylococcal isolates was also tested. Children admitted in paediatric wards with IVD for more than 48 h were enrolled. Blood, IVD tip at the time of removal, skin swab at the site of insertion of IVD and nasal swab were collected and cultured by standard protocol. All staphylococcal isolates from any source were analyzed for antimicrobial susceptibility by disk diffusion method. Genotyping matching of those staphylococcal isolates was done which were isolated from different sites of the same patient, but were phonotypically similar. Genotype of blood isolate was compared with genotype of isolate from nose/IVD/skin. Staph...
Protein Expression and Purification, 2014
Collagen constitutes one of the vital components of the basement membrane scaffolds. Noncollageno... more Collagen constitutes one of the vital components of the basement membrane scaffolds. Noncollagenous domains (NC1) derived from collagens exhibit potent anti-angiogenic properties, thus attaining significance in regulation of angiogenesis promoted diseases. Individual NC1 domains essential for anti-angiogenic evaluations are generally obtained through purification of individual non-collagenous domains, which have undergone steady developments for enhancing the yields, purpose of biological evaluations and solubility based on the nature of different NC1 domains. This review focuses on the method developments in obtaining biologically active NC1 domains and for specific evaluations in different scenarios.
Protein & Peptide Letters, 2012
Oral Diseases, 2010
This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia an... more This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis are synergistic in terms of virulence potential using a model of mixed-microbial infection in rats. Three groups of rats were infected orally with either T. forsythia or P. gingivalis in mono-bacterial infections or as mixed-microbial infections for 12 weeks and a sham-infected group were used as a control. This study examined bacterial infection, inflammation, immunity, and alveolar bone loss changes with disease progression. Tannerella forsythia and P. gingivalis genomic DNA was detected in microbial samples from infected rats by PCR indicating their colonization in the rat oral cavity. Primary infection induced significantly high IgG, IgG2b, IgG1, and IgG2a antibody levels indicating activation of mixed Th1 and Th2 immune responses. Rats infected with the mixed-microbial consortium exhibited significantly increased palatal horizontal and interproximal alveolar bone loss. Histological examinations indicated significant hyperplasia of the gingival epithelium with moderate inflammatory infiltration and apical migration of junctional epithelium. The results observed differ compared to uninfected controls. Our results indicated that T. forsythia and P. gingivalis exhibit virulence, but not virulence synergy, resulting in the immuno-inflammatory responses and lack of humoral immune protection during periodontitis in rats.
Molecular Oral Microbiology, 2010
Introduction-Porphyromonas gingivalis has been associated with subgingival biofilms in adult peri... more Introduction-Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. The objectives of this investigation were to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. Methods-P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip® arrays to provide a molecular profile of the events that occur following infection of these tissues. Results-After P. gingivalis infection, 5517 and 1900 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P ≤ 0.05) and up-regulated. Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B cell receptor signaling, TGF-β cytokine family receptor signaling, and MHC class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T cell stimulation, and down regulation of antiviral and T cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption.
Journal of the American College of Cardiology, 2010
Background: Prior studies have detected periodontal bacterial genomic DNA, including Porphyromona... more Background: Prior studies have detected periodontal bacterial genomic DNA, including Porphyromonas gingivalis (Pg), in atherosclerotic lesions. Two potent viral anti-inflammatory proteins (VPs), Serp-1 (protease inhibitor) and M-T7 (chemokine binding protein) inhibit vascular inflammation and plaque growth in animal models and in a pilot clinical study in acute coronary syndromes (Serp-1). Methods: We have examined the effects of the VPs in ApoEnull mice with P. gingivalis infection with and without angioplasty injury. methods. ApoEnull mice had balloon angioplasty (BA) injury followed by Serp-1, MT-7, or control saline i.v. infusion. Subsequently, mice were infected with P. gingivalis strain 381 as oral gavage over 20 weeks with assessment of periodontal disease and atherosclerosis. Oral bacterial samples were collected and colonization/infection assessed by PCR. Mice were euthanized at 20 weeks after infection. Serum IgG antibody, alveolar bone resorption (ABR), atherosclerotic plaque growth, inflammatory mononuclear cell, and bacterial genomic DNA responses to P. gingivalis infections are being evaluated by ELISA, morphometry, histomorphometry and PCR, respectively. Results: PCR detected P. gingivalis in nearly all mice throughout the experimental interval. All mice infected with P. gingivalis demonstrated elevated IgG antibody compared to control mice. P. gingivalis induced greater maxillary and mandibular (buccal and palatal) horizontal ABR than control mice. P. gingivalis increased mononuclear cell invasion and intimal plaque to medal ratios in the abdominal aorta of non injured ApoEnull mice (P < 0.017) but not in mice with angioplasty injury (P = 0.17) when compared to uninfected control mice. Serp-1 and MT-7 inhibited intimal plaque and inflammatory mononuclear cell invasion in mice after angioplasty injury (P < 0.04). Conclusions: This is the first study demonstrating virus derived anti-inflammatory protein (VP) modulation of plaque growth after angioplasty injury during active P. gingivalis periodontal infection in ApoEnull mice. VP treatment has the capacity to reduce monocye invasion and plaque growth even during active oral bacterial infection. CORE Metadata, citation and similar papers at core.ac.uk
Journal of the American College of Cardiology, 2006
We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous... more We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous emergency treatment of pulmonary embolism. BACKGROUND If thrombolysis is contraindicated or recanalization by thrombolysis delayed in patients with severe pulmonary embolism who are threatened by acute circulatory failure, percutaneous temporary pulmonary stent placement may represent an additional option before surgical embolectomy is considered. METHODS The newly designed temporary pulmonary stent is made from woven Nitinol and has a distal blunt end and a proximal crimped end, which is firmly fixed to a 0.035-inch guidewire. It is delivered through a 9.5-F polytetrafluoroethylene sheath using a pusher tube. Stent placement and removal were examined in 9 anesthetized sheep with experimentally induced pulmonary embolism. Hemodynamic parameters were recorded in 7 animals. RESULTS Delivery and removal of the stent was uneventful and rapidly accomplished. Stent placement was associated with a significant decrease in Miller angiographic index (from 11.2 Ϯ 3.1 to 3.8 Ϯ 1.9; p ϭ 0.0001), heart rate (from 139 Ϯ 35 beats/min to 92 Ϯ 11 beats/min; p ϭ 0.0129), and mean pulmonary artery pressure (from 32 Ϯ 14 mm Hg to 21 Ϯ 14 mm Hg; p ϭ 0.0029) and a significant increase in mean aortic pressure (from 48 Ϯ 14 mm Hg to 61 Ϯ 8 mm Hg; p ϭ 0.0080). Autopsy revealed neither wall damage nor parenchymal hemorrhage. CONCLUSIONS Our preliminary study proves the technical feasibility of temporary placement and removal of a newly designed dedicated pulmonary stent to recanalize centrally located embolic occlusions in severe pulmonary embolism. Animal experimental evaluation revealed rapid and significant circulatory improvement after stent placement.
Journal of Microbiological Methods, 2003
A sandwich dot enzyme-linked immunosorbent assay (ELISA) was standardized to detect mycobacterial... more A sandwich dot enzyme-linked immunosorbent assay (ELISA) was standardized to detect mycobacterial antigen in fine needle aspirates of patients with tubercular lymphadenitis (TBLN). The assay was performed on nitrocellulose paper by using antibodies raised in mice and rabbits against crude soluble protein (CSP) of Mycobacterium tuberculosis. The test was able to detect as low as 5 ng protein/ml. A total of 225 suspected cases of tubercular lymphadenopathy were screened, out of which 96 were cytomorphologically confirmed as cases of tubercular lymphadenitis (50 acid-fast bacilli (AFB)-positive and 46 AFBnegative). These were considered as positive controls. Only 28 cases were proven to be of nontubercular etiology and were considered as negative controls. In the remaining 101 (39 scanty) aspirates, tubercular etiology could neither be ruled out nor confirmed. Out of 50 AFB-positive confirmed cases of tubercular lymphadenitis, 46 were ELISA-positive. Out of 46 AFBnegative but cytomorphologically confirmed aspirates, antigen could be demonstrated in only 42 aspirates. Four samples from patients with nontubercular etiology were also found to be ELISA-positive. Antigen was picked up in a total of 90.3% of aspirates with suspicion of tuberculosis and 79.5% of scanty aspirates. The assay was found to be 91.6% sensitive and 85.7% specific. The assay was found to be simple and rapid, and hence, could be performed in areas where health facilities are rudimentary.
Journal of Medical Microbiology, 2008
Staphylococci are the main causative agents of nosocomial diseases. Over the last few years, the ... more Staphylococci are the main causative agents of nosocomial diseases. Over the last few years, the increase in the number of meticillin-resistant (MR) staphylococci has become a major clinical problem. Accuracy and promptness in the detection of meticillin resistance are of key importance in ensuring the correct antibiotic treatment in infected patients and control of MR staphylococci in the hospital environment. This study evaluated the accuracy of a cefoxitin disc diffusion (DD) test for the detection of meticillin resistance in staphylococci. A total of 144 clinical isolates [97 Staphylococcus aureus and 47 coagulase-negative staphylococci (CoNS)] were tested using a mecA gene PCR, a DD test (oxacillin, 1 mg disc; cefoxitin, 30 mg disc), determination of oxacillin MIC by agar dilution (AD), and an oxacillin screen agar test at oxacillin concentrations of 4 and 6 mg ml "1. Of the 97 S. aureus and 47 CoNS isolates, 73 (75.26 %) and 30 (63.83 %), respectively, were mecA-positive. The sensitivity and specificity of the cefoxitin DD test were 94.44 and 95.83 %, respectively, for S. aureus and 80 and 100 %, respectively, for CoNS. The oxacillin DD method was 100 % sensitive and 58.33 % specific for S. aureus, and 86.67 % sensitive and 70.59 % specific for CoNS. The AD test was highly sensitive (98.63 %) and specific (98.53 %) for S. aureus and CoNS (83.33 % sensitive and 94.12 % specific). The cefoxitin DD test for meticillin-resistance detection was more specific but less sensitive than the oxacillin DD test. Use of DD tests for both cefoxitin and oxacillin can help in more accurate prediction of meticillin resistance. Centres that are not equipped to carry out PCR can use AD methods for confirmation of meticillin resistance, especially in oxacillin-resistant and cefoxitin-sensitive cases.
Journal of Experimental Medicine, 2010
CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan para... more CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course ...
Journal of Biological Chemistry, 2013
Background: Jak3 is a tyrosine kinase, and its role in mucosal differentiation is not known. Resu... more Background: Jak3 is a tyrosine kinase, and its role in mucosal differentiation is not known. Results: Jak3, expressed in colonic mucosa, was essential for differentiation, goblet cell surface localization, muc2 expression, and epithelial barrier functions. Conclusion: Jak3 plays a protective role against predisposition to colitis by promoting mucosal differentiation. Significance: Understanding mucosal functions of Jak3 has important implications for patients with inflammatory bowel disease.
Investigative Radiology, 2006
Objective: The authors studied the development of a thrombectomy device that is adequately steera... more Objective: The authors studied the development of a thrombectomy device that is adequately steerable and quickly placeable in case of extensive pulmonary embolism. Materials and Methods: The device consists of a self-expandable nitinol basket mounted at a catheter-tip, which allows suction and extraction of thrombus material. Five in vitro tests were performed followed by tests in 6 sheep. In vivo thrombus material was introduced through a jugular vein to produce pulmonary embolism. After catheter insertion over the right femoral vein, the basket was placed adjacent to the pulmonary embolus and the extraction procedure was performed. Results: In in vitro tests, the extracted thrombus amount varied between 60% and 95%. In animal experiments, the extracted amount varied between 30% and 95% as determined angiographically. Limiting factors were steerability and optimal positioning of the basket in relation to the embolus. Conclusions: Extraction of pulmonary embolism with the selfexpanding suction basket is feasible. However, successful recanalization is limited by catheter maneuverability in the pulmonary arterial system.
Investigative Opthalmology & Visual Science, 2013
Inhibition of elastin peptidemediated angiogenic signaling mechanism(s) in choroidal endothelial ... more Inhibition of elastin peptidemediated angiogenic signaling mechanism(s) in choroidal endothelial cells by the a6(IV)NC1 collagen fragment.
Infection and Immunity, 2010
Porphyromonas gingivalis secretes a serine phosphatase enzyme, SerB, upon contact with gingival e... more Porphyromonas gingivalis secretes a serine phosphatase enzyme, SerB, upon contact with gingival epithelial cells in vitro . The SerB protein plays a critical role in internalization and survival of the organism in epithelial cells. SerB is also responsible for the inhibition of interleukin-8 (IL-8) secretion from gingival epithelial cells infected with P. gingivalis . This study examined the ability of a P. gingivalis SerB mutant to colonize the oral cavity and induce gingival inflammation, immune responses, and alveolar bone resorption in a rat model of periodontal disease. Both P. gingivalis ATCC 33277 and an isogenic ΔSerB mutant colonized the oral cavities of rats during the 12-week experimental period. Both of the strains induced significant ( P < 0.05) systemic levels of immunoglobulin G (IgG) and isotypes IgG1, IgG2a, and IgG2b, indicating the involvement of both T helper type 1 (Th1) and Th2 responses to infection. Both strains induced significantly ( P < 0.05) higher ...
Periodontal diseases are complex, multifactorial, polymicrobial immunoinflammatory infections. A ... more Periodontal diseases are complex, multifactorial, polymicrobial immunoinflammatory infections. A prominent pathogenic consortium in subgingval biofilms in human periodontitis includes Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf). Objective: The study examined alveolar bone resorption induced by periodontal pathogens P. gingivalis, T. denticola, and T. forsythia in monomicrobial and mixed microbial periodontal disease in rats. Methods: Adult rats were infected with P. gingivalis and T. denticola as oral gavage. Oral infections were induced either as monobacterial (Pg, Td) or mixed microbial (Pg+Td). Rats were euthanized at 6 and 12 weeks following exposure to bacteria and subsequent induction of periodontal disease. The jaws were removed, autoclaved, defleshed, maxilla and mandibles separated, and alveolar bone loss was evaluated using radiography. Digital radiographs were acquired with orthogonal projection geometry using an exposure time of...
India Quarterly: A Journal of International Affairs, 2015
Jha, Prashant, Battles of the New Republic: A Contemporary History of Nepal (New Delhi: Aleph Boo... more Jha, Prashant, Battles of the New Republic: A Contemporary History of Nepal (New Delhi: Aleph Book Publication, 2014). Pp. 358, Price ₹ 395.
PLoS ONE, 2014
Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Tr... more Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virusderived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE 2/2 mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P,0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P,0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE 2/2 mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine proteases significantly reduced arterial plaque growth, suggesting a central role for chemokine-mediated inflammation after BA in P. gingivalis infected mice.
Scientific Reports, 2014
a1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this biological function was partl... more a1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this biological function was partly attributed a1(IV)NC1 binding to a1b1-integrin. However, its potent antiangiogenic activity and the molecular targets of a1(IV)NC1 has not been investigated. In the present study, the regulation of MMP-2 activation by a1(IV)NC1 was evaluated. a1b1-integrin which is required for inhibition of angiogenesis is not playing a role in cellular invasion and inhibition of MMP-2 activation by a1(IV)NC1. We found that a1(IV)NC1 binds the CBD of MMP-2 and forming a stable complex that prevents activation of MMP-2. The antiangiogenic activity of a1(IV)NC1 is mediated, in part, by this binding activity. In addition, up-regulation of TIMP-2 by a1(IV)NC1 led to saturation of MT1-MMP binding sites, which in turn led to inhibition of MMP-2 activation. In-vivo studies using a1-integrin null-mice treated with higher doses of a1(IV)NC1 showed integrin independent inhibition of tumor growth and active-MMP-2, without affecting MMP-9, MMP-7 and angiostatin. D uring vascular basement membranes (VBM) remodeling, crucial circulating angiogenic and antiangiogenic molecules are liberated that controls formation of new capillaries 1,2. Remodeling of basement membrane and de-novo expression of provisional matrix proteins promote cell adhesion, migration and differentiation that play important roles in angiogenesis 1,2. Angiogenesis is one of the most consistent host responses associated with cancer tumor angiogenesis which is partly regulated by endogenous angiogenesis inhibitors that are released from VBM upon proteolysis 3-9. The endogenous angiogenesis inhibitors released from VBM includes some of the type IV collagen derived non-collagenous domains (NC1) that are liberated from extracellular matrix (ECM) by matrix metalloproteinases (MMPs) 5,7,10-13. ECM degradation by MMPs is prerequisite during tumor growth and metastasis 14-18. MMPs exist as both soluble and membrane-anchored types (MT-MMPs) 19. Soluble MMPs are responsible for ECM degradation, whereas MT-MMPs participate in pericellular VBM degradation 20. The cell surface activation of proMMP-2 by MT1-MMP is pivotal in tumor invasion following degradation of VBM by MMP-2 21. The major component of vascular basement membrane (VBM) is type IV collagen. Type IV collagen have a1-a6 chains and have important roles in the assembly of BM 22,23. Remodeling of VBM can provide crucial angiogenic and anti-angiogenic molecules to control the formation of new capillaries 1,24,25. Such anti-angiogenic molecules of VBM include NC1 domain of a1-chains of type IV collagen 10,21,26-28. The C-terminal non-collagenous domain from a1-chain of type IV collagen, a1(IV)NC1 (arresten) is a 26-kDa protein induced by p53 that binds to a1b1-integrin and mediates its antiangiogenic actions and suppresses invasion of squamous cell carcinoma 10,21,26,29-31. a1(IV)NC1 and its N-and C-terminal domains are promoting apoptosis 27,32. In addition we also showed that a1(IV)NC1 inhibits MMP-2 activation without affecting expression 28. Despite its potent in-vitro and in-vivo antiangiogenic activity, the molecular targets of a1(IV)NC1 are yet to be identified. In the present study, we reported that a1(IV)NC1 inhibits invasion and MMP-2 activation by forming a complex with collagen binding domain (CBD) of MMP-2. These findings demonstrate that a1(IV)NC1 regulates MMP2 activation without affecting circulating MMP-9, 27 and angiostatin activation in-vitro and in-vivo. This regulation of MMP-2 activation contributes a1(IV)NC1 mediated regression of tumor angiogenesis in mice. These findings indicate that a novel MMP-2 regulatory mechanism of a1(IV)NC1 that partly regulate its anti-angiogenic and anti-tumorogenic activity.
PLoS ONE, 2013
Object: Antiangiogenic treatments are beginning to give promising outcomes in many vascular disea... more Object: Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and pro-apoptotic actions of a1(IV)NC1 and its N-and C-peptides a1S1(IV)NC1, a1S2(IV)NC1 were investigated in-vitro and in-vivo. Study Method: Endothelial cells (ECs) were treated with a1(IV)NC1, a1S1(IV)NC1, a1S2(IV)NC1 and in-vitro proliferation, migration, tube formation and apoptotic assays were executed. FasL, Fas, Caspase-8,-3 and PARP activations were studied using immunoblotting analysis using specific antibodies. Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using a1(IV)NC1 in a mice model. Results: Like a1(IV)NC1, its N-and C-terminal a1S2(IV)NC1 and a1S1(IV)NC1 domains posses anti-proliferative, proapoptotic activity and inhibit ECs migration and tube formation in-vitro. Both a1S1(IV)NC1 and a1S2(IV)NC1 domains promote apoptosis by activating FasL and down stream apoptotic events including activation of caspase-8,-3 and PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed apoptotic TUNEL positive microvasculature upon a1(IV)NC1 treatment, indicating inhibition of tumor angiogenesis and tumor growth. Further, the antitumor activity of a1(IV)NC1 was abrogated when caspase-3 inhibitor was used. These results conform additional properties of a1(IV)NC1 as an endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by activating FasL mediated caspase-3. Significance: a1(IV)NC1 and its N-and C-terminal a1S1(IV)NC1 and a1S2(IV)NC1 domains also posses pro-apoptotic and angioinhibitory activity in-vitro and in-vivo. a1(IV)NC1 regulates tumor angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These results demonstrate that a1(IV)NC1 and its peptides inhibit neo-vascular diseases.
The Indian journal of medical research, 2003
As isolation of Mycobacterium tuberculosis in culture requires a long time, there is a need for s... more As isolation of Mycobacterium tuberculosis in culture requires a long time, there is a need for simple rapid method for direct detection of M. tuberculosis from clinical specimens. Amplified nucleic acid hybridization assays such as polymerase chain reaction (PCR) have shown promising results. In the present study, the sensitivity of PCR assay was assessed over smear microscopy for rapid diagnosis of tuberculosis in pulmonary and extra-pulmonary samples from patients suspected to have tuberculosis. A total of 37 clinical samples from patients with pulmonary tuberculosis and 133 from patients with extra-pulmonary tuberculosis were subjected to Ziehl-Neelsen staining for smear preparation and PCR for detection of mycobacterial DNA. It was observed that 100 per cent of acid fast bacilli (AFB) positive and 35.7 per cent of AFB negative pulmonary samples and 82.76 per cent of AFB positive and 56.73 per cent of AFB negative extra-pulmonary samples were positive for mycobacterial DNA detec...
The Indian journal of medical research, 2011
Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are m... more Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are major cause of morbidity and mortality. The present study was carried out to assess the frequency of staphylococcal IVD associated infections in a paediatric ward of a tertiary case hospital. Prevalence of resistance to commonly used antimicrobials in hospital acquired staphylococcal isolates was also tested. Children admitted in paediatric wards with IVD for more than 48 h were enrolled. Blood, IVD tip at the time of removal, skin swab at the site of insertion of IVD and nasal swab were collected and cultured by standard protocol. All staphylococcal isolates from any source were analyzed for antimicrobial susceptibility by disk diffusion method. Genotyping matching of those staphylococcal isolates was done which were isolated from different sites of the same patient, but were phonotypically similar. Genotype of blood isolate was compared with genotype of isolate from nose/IVD/skin. Staph...
Protein Expression and Purification, 2014
Collagen constitutes one of the vital components of the basement membrane scaffolds. Noncollageno... more Collagen constitutes one of the vital components of the basement membrane scaffolds. Noncollagenous domains (NC1) derived from collagens exhibit potent anti-angiogenic properties, thus attaining significance in regulation of angiogenesis promoted diseases. Individual NC1 domains essential for anti-angiogenic evaluations are generally obtained through purification of individual non-collagenous domains, which have undergone steady developments for enhancing the yields, purpose of biological evaluations and solubility based on the nature of different NC1 domains. This review focuses on the method developments in obtaining biologically active NC1 domains and for specific evaluations in different scenarios.
Protein & Peptide Letters, 2012
Oral Diseases, 2010
This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia an... more This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis are synergistic in terms of virulence potential using a model of mixed-microbial infection in rats. Three groups of rats were infected orally with either T. forsythia or P. gingivalis in mono-bacterial infections or as mixed-microbial infections for 12 weeks and a sham-infected group were used as a control. This study examined bacterial infection, inflammation, immunity, and alveolar bone loss changes with disease progression. Tannerella forsythia and P. gingivalis genomic DNA was detected in microbial samples from infected rats by PCR indicating their colonization in the rat oral cavity. Primary infection induced significantly high IgG, IgG2b, IgG1, and IgG2a antibody levels indicating activation of mixed Th1 and Th2 immune responses. Rats infected with the mixed-microbial consortium exhibited significantly increased palatal horizontal and interproximal alveolar bone loss. Histological examinations indicated significant hyperplasia of the gingival epithelium with moderate inflammatory infiltration and apical migration of junctional epithelium. The results observed differ compared to uninfected controls. Our results indicated that T. forsythia and P. gingivalis exhibit virulence, but not virulence synergy, resulting in the immuno-inflammatory responses and lack of humoral immune protection during periodontitis in rats.
Molecular Oral Microbiology, 2010
Introduction-Porphyromonas gingivalis has been associated with subgingival biofilms in adult peri... more Introduction-Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. The objectives of this investigation were to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. Methods-P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip® arrays to provide a molecular profile of the events that occur following infection of these tissues. Results-After P. gingivalis infection, 5517 and 1900 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P ≤ 0.05) and up-regulated. Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B cell receptor signaling, TGF-β cytokine family receptor signaling, and MHC class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T cell stimulation, and down regulation of antiviral and T cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption.
Journal of the American College of Cardiology, 2010
Background: Prior studies have detected periodontal bacterial genomic DNA, including Porphyromona... more Background: Prior studies have detected periodontal bacterial genomic DNA, including Porphyromonas gingivalis (Pg), in atherosclerotic lesions. Two potent viral anti-inflammatory proteins (VPs), Serp-1 (protease inhibitor) and M-T7 (chemokine binding protein) inhibit vascular inflammation and plaque growth in animal models and in a pilot clinical study in acute coronary syndromes (Serp-1). Methods: We have examined the effects of the VPs in ApoEnull mice with P. gingivalis infection with and without angioplasty injury. methods. ApoEnull mice had balloon angioplasty (BA) injury followed by Serp-1, MT-7, or control saline i.v. infusion. Subsequently, mice were infected with P. gingivalis strain 381 as oral gavage over 20 weeks with assessment of periodontal disease and atherosclerosis. Oral bacterial samples were collected and colonization/infection assessed by PCR. Mice were euthanized at 20 weeks after infection. Serum IgG antibody, alveolar bone resorption (ABR), atherosclerotic plaque growth, inflammatory mononuclear cell, and bacterial genomic DNA responses to P. gingivalis infections are being evaluated by ELISA, morphometry, histomorphometry and PCR, respectively. Results: PCR detected P. gingivalis in nearly all mice throughout the experimental interval. All mice infected with P. gingivalis demonstrated elevated IgG antibody compared to control mice. P. gingivalis induced greater maxillary and mandibular (buccal and palatal) horizontal ABR than control mice. P. gingivalis increased mononuclear cell invasion and intimal plaque to medal ratios in the abdominal aorta of non injured ApoEnull mice (P < 0.017) but not in mice with angioplasty injury (P = 0.17) when compared to uninfected control mice. Serp-1 and MT-7 inhibited intimal plaque and inflammatory mononuclear cell invasion in mice after angioplasty injury (P < 0.04). Conclusions: This is the first study demonstrating virus derived anti-inflammatory protein (VP) modulation of plaque growth after angioplasty injury during active P. gingivalis periodontal infection in ApoEnull mice. VP treatment has the capacity to reduce monocye invasion and plaque growth even during active oral bacterial infection. CORE Metadata, citation and similar papers at core.ac.uk
Journal of the American College of Cardiology, 2006
We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous... more We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous emergency treatment of pulmonary embolism. BACKGROUND If thrombolysis is contraindicated or recanalization by thrombolysis delayed in patients with severe pulmonary embolism who are threatened by acute circulatory failure, percutaneous temporary pulmonary stent placement may represent an additional option before surgical embolectomy is considered. METHODS The newly designed temporary pulmonary stent is made from woven Nitinol and has a distal blunt end and a proximal crimped end, which is firmly fixed to a 0.035-inch guidewire. It is delivered through a 9.5-F polytetrafluoroethylene sheath using a pusher tube. Stent placement and removal were examined in 9 anesthetized sheep with experimentally induced pulmonary embolism. Hemodynamic parameters were recorded in 7 animals. RESULTS Delivery and removal of the stent was uneventful and rapidly accomplished. Stent placement was associated with a significant decrease in Miller angiographic index (from 11.2 Ϯ 3.1 to 3.8 Ϯ 1.9; p ϭ 0.0001), heart rate (from 139 Ϯ 35 beats/min to 92 Ϯ 11 beats/min; p ϭ 0.0129), and mean pulmonary artery pressure (from 32 Ϯ 14 mm Hg to 21 Ϯ 14 mm Hg; p ϭ 0.0029) and a significant increase in mean aortic pressure (from 48 Ϯ 14 mm Hg to 61 Ϯ 8 mm Hg; p ϭ 0.0080). Autopsy revealed neither wall damage nor parenchymal hemorrhage. CONCLUSIONS Our preliminary study proves the technical feasibility of temporary placement and removal of a newly designed dedicated pulmonary stent to recanalize centrally located embolic occlusions in severe pulmonary embolism. Animal experimental evaluation revealed rapid and significant circulatory improvement after stent placement.
Journal of Microbiological Methods, 2003
A sandwich dot enzyme-linked immunosorbent assay (ELISA) was standardized to detect mycobacterial... more A sandwich dot enzyme-linked immunosorbent assay (ELISA) was standardized to detect mycobacterial antigen in fine needle aspirates of patients with tubercular lymphadenitis (TBLN). The assay was performed on nitrocellulose paper by using antibodies raised in mice and rabbits against crude soluble protein (CSP) of Mycobacterium tuberculosis. The test was able to detect as low as 5 ng protein/ml. A total of 225 suspected cases of tubercular lymphadenopathy were screened, out of which 96 were cytomorphologically confirmed as cases of tubercular lymphadenitis (50 acid-fast bacilli (AFB)-positive and 46 AFBnegative). These were considered as positive controls. Only 28 cases were proven to be of nontubercular etiology and were considered as negative controls. In the remaining 101 (39 scanty) aspirates, tubercular etiology could neither be ruled out nor confirmed. Out of 50 AFB-positive confirmed cases of tubercular lymphadenitis, 46 were ELISA-positive. Out of 46 AFBnegative but cytomorphologically confirmed aspirates, antigen could be demonstrated in only 42 aspirates. Four samples from patients with nontubercular etiology were also found to be ELISA-positive. Antigen was picked up in a total of 90.3% of aspirates with suspicion of tuberculosis and 79.5% of scanty aspirates. The assay was found to be 91.6% sensitive and 85.7% specific. The assay was found to be simple and rapid, and hence, could be performed in areas where health facilities are rudimentary.
Journal of Medical Microbiology, 2008
Staphylococci are the main causative agents of nosocomial diseases. Over the last few years, the ... more Staphylococci are the main causative agents of nosocomial diseases. Over the last few years, the increase in the number of meticillin-resistant (MR) staphylococci has become a major clinical problem. Accuracy and promptness in the detection of meticillin resistance are of key importance in ensuring the correct antibiotic treatment in infected patients and control of MR staphylococci in the hospital environment. This study evaluated the accuracy of a cefoxitin disc diffusion (DD) test for the detection of meticillin resistance in staphylococci. A total of 144 clinical isolates [97 Staphylococcus aureus and 47 coagulase-negative staphylococci (CoNS)] were tested using a mecA gene PCR, a DD test (oxacillin, 1 mg disc; cefoxitin, 30 mg disc), determination of oxacillin MIC by agar dilution (AD), and an oxacillin screen agar test at oxacillin concentrations of 4 and 6 mg ml "1. Of the 97 S. aureus and 47 CoNS isolates, 73 (75.26 %) and 30 (63.83 %), respectively, were mecA-positive. The sensitivity and specificity of the cefoxitin DD test were 94.44 and 95.83 %, respectively, for S. aureus and 80 and 100 %, respectively, for CoNS. The oxacillin DD method was 100 % sensitive and 58.33 % specific for S. aureus, and 86.67 % sensitive and 70.59 % specific for CoNS. The AD test was highly sensitive (98.63 %) and specific (98.53 %) for S. aureus and CoNS (83.33 % sensitive and 94.12 % specific). The cefoxitin DD test for meticillin-resistance detection was more specific but less sensitive than the oxacillin DD test. Use of DD tests for both cefoxitin and oxacillin can help in more accurate prediction of meticillin resistance. Centres that are not equipped to carry out PCR can use AD methods for confirmation of meticillin resistance, especially in oxacillin-resistant and cefoxitin-sensitive cases.
Journal of Experimental Medicine, 2010
CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan para... more CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course ...
Journal of Biological Chemistry, 2013
Background: Jak3 is a tyrosine kinase, and its role in mucosal differentiation is not known. Resu... more Background: Jak3 is a tyrosine kinase, and its role in mucosal differentiation is not known. Results: Jak3, expressed in colonic mucosa, was essential for differentiation, goblet cell surface localization, muc2 expression, and epithelial barrier functions. Conclusion: Jak3 plays a protective role against predisposition to colitis by promoting mucosal differentiation. Significance: Understanding mucosal functions of Jak3 has important implications for patients with inflammatory bowel disease.
Investigative Radiology, 2006
Objective: The authors studied the development of a thrombectomy device that is adequately steera... more Objective: The authors studied the development of a thrombectomy device that is adequately steerable and quickly placeable in case of extensive pulmonary embolism. Materials and Methods: The device consists of a self-expandable nitinol basket mounted at a catheter-tip, which allows suction and extraction of thrombus material. Five in vitro tests were performed followed by tests in 6 sheep. In vivo thrombus material was introduced through a jugular vein to produce pulmonary embolism. After catheter insertion over the right femoral vein, the basket was placed adjacent to the pulmonary embolus and the extraction procedure was performed. Results: In in vitro tests, the extracted thrombus amount varied between 60% and 95%. In animal experiments, the extracted amount varied between 30% and 95% as determined angiographically. Limiting factors were steerability and optimal positioning of the basket in relation to the embolus. Conclusions: Extraction of pulmonary embolism with the selfexpanding suction basket is feasible. However, successful recanalization is limited by catheter maneuverability in the pulmonary arterial system.
Investigative Opthalmology & Visual Science, 2013
Inhibition of elastin peptidemediated angiogenic signaling mechanism(s) in choroidal endothelial ... more Inhibition of elastin peptidemediated angiogenic signaling mechanism(s) in choroidal endothelial cells by the a6(IV)NC1 collagen fragment.
Infection and Immunity, 2010
Porphyromonas gingivalis secretes a serine phosphatase enzyme, SerB, upon contact with gingival e... more Porphyromonas gingivalis secretes a serine phosphatase enzyme, SerB, upon contact with gingival epithelial cells in vitro . The SerB protein plays a critical role in internalization and survival of the organism in epithelial cells. SerB is also responsible for the inhibition of interleukin-8 (IL-8) secretion from gingival epithelial cells infected with P. gingivalis . This study examined the ability of a P. gingivalis SerB mutant to colonize the oral cavity and induce gingival inflammation, immune responses, and alveolar bone resorption in a rat model of periodontal disease. Both P. gingivalis ATCC 33277 and an isogenic ΔSerB mutant colonized the oral cavities of rats during the 12-week experimental period. Both of the strains induced significant ( P < 0.05) systemic levels of immunoglobulin G (IgG) and isotypes IgG1, IgG2a, and IgG2b, indicating the involvement of both T helper type 1 (Th1) and Th2 responses to infection. Both strains induced significantly ( P < 0.05) higher ...