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  • 1
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    Online Resource
    Table_2.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-12-16)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-12-16)
    Abstract: Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in the ITGβ2 gene. LAD type 2 (LAD2) is caused by mutations in the SLC35C1 gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in the FERMT3 gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in the FERMT3 gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1 + ) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in the ITGβ2 gene, and 4 novel mutations were detected in the FERMT3 gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.612703
    DOI: 10.3389/fimmu.2020.612703.s001
    DOI: 10.3389/fimmu.2020.612703.s002
    DOI: 10.3389/fimmu.2020.612703.s003
    DOI: 10.3389/fimmu.2020.612703.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 11 ( 2021-1-15)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2021-1-15)
    Abstract: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India. Methods Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria. Results We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae , Staphylococcus aureus and Klebsiella pneumoniae . Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients. Conclusion There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.612323
    DOI: 10.3389/fimmu.2020.612323.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Influence of cation–π interactions to the structural stability of prokaryotic and eukaryotic translation elongation factors
    Springer Science and Business Media LLC ; 2009
    In:  Protoplasma Vol. 238, No. 1-4 ( 2009-12), p. 11-20
    Details
    In: Protoplasma, Springer Science and Business Media LLC, Vol. 238, No. 1-4 ( 2009-12), p. 11-20
    Type of Medium: Online Resource
    ISSN: 0033-183X , 1615-6102
    URL: Article
    DOI: 10.1007/s00709-009-0066-3
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 1463033-3
    SSG: 12
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  • 4
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    A Versatile Reporter System To Monitor Virus-Infected Cells and Its Application to Dengue Virus and SARS-CoV-2
    American Society for Microbiology ; 2021
    In:  Journal of Virology Vol. 95, No. 4 ( 2021-01-28)
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    In: Journal of Virology, American Society for Microbiology, Vol. 95, No. 4 ( 2021-01-28)
    Abstract: Positive-strand RNA viruses have been the etiological agents in several major disease outbreaks over the last few decades. Examples of this include flaviviruses, such as dengue virus and Zika virus, which cause millions of yearly infections around the globe, and coronaviruses, such as SARS-CoV-2, the source of the current pandemic. The severity of outbreaks caused by these viruses stresses the importance of research aimed at determining methods to limit virus spread and to curb disease severity. Such studies require molecular tools to decipher virus-host interactions and to develop effective treatments. Here, we describe the generation and characterization of a reporter system that can be used to visualize and identify cells infected with dengue virus or SARS-CoV-2. This system is based on viral protease activity that mediates cleavage and nuclear translocation of an engineered fluorescent protein stably expressed in cells. We show the suitability of this system for live cell imaging, for visualization of single infected cells, and for screening and testing of antiviral compounds. With the integrated modular building blocks, this system is easy to manipulate and can be adapted to any virus encoding a protease, thus offering a high degree of flexibility. IMPORTANCE Reporter systems are useful tools for fast and quantitative visualization of virus-infected cells within a host cell population. Here, we describe a reporter system that takes advantage of virus-encoded proteases expressed in infected cells to cleave an ER-anchored fluorescent protein fused to a nuclear localization sequence. Upon cleavage, the GFP moiety translocates to the nucleus, allowing for rapid detection of the infected cells. Using this system, we demonstrate reliable reporting activity for two major human pathogens from the Flaviviridae and the Coronaviridae families: dengue virus and SARS-CoV-2. We apply this reporter system to live cell imaging and use it for proof-of-concept to validate antiviral activity of a nucleoside analogue. This reporter system is not only an invaluable tool for the characterization of viral replication, but also for the discovery and development of antivirals that are urgently needed to halt the spread of these viruses.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01715-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1495529-5
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  • 5
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    Chemical Induction of Unfolded Protein Response Enhances Cancer Cell Killing through Lytic Virus Infection
    American Society for Microbiology ; 2014
    In:  Journal of Virology Vol. 88, No. 22 ( 2014-11-15), p. 13086-13098
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 88, No. 22 ( 2014-11-15), p. 13086-13098
    Abstract: Cancer cells are susceptible to oncolytic viruses, albeit variably. Human adenoviruses (HAdVs) are widely used oncolytic agents that have been engineered to produce progeny within the tumor and elicit bystander effects. We searched for host factors enhancing bystander effects and conducted a targeted RNA interference screen against guanine nucleotide exchange factors (GEFs) of small GTPases. We show that the unfolded protein response (UPR), which is readily inducible in aggressive tumor cells, enhances melanoma or epithelial cancer cell killing upon HAdV infection. UPR was triggered by knockdown of Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF-1) or the GBF-1 inhibitor golgicide A (GCA) and stimulated HAdV infection. GBF-1 is a GEF for ADP ribosylation factors (Arfs) regulating endoplasmic reticulum (ER)-to-Golgi apparatus and intra-Golgi apparatus membrane transport. Cells treated with GCA enhanced HAdV-induced cytopathic effects in epithelial and melanoma cancer cells but not normal cells, if the drug was applied several hours prior to HAdV inoculation. This was shown by real-time label-free impedance measurements using the xCELLigence system. GCA-treated cells contained fewer incoming HAdVs than control cells, but GCA treatment boosted HAdV titers and spreading in cancer cells. GCA enhanced viral gene expression or transgene expression from the cytomegalovirus promoter of B- or C-species HAdVs but did not enhance viral early region 1A (E1A) expression in uninfected cell lines or cells transfected with plasmid reporter DNA. The UPR-enhanced cell killing required the nuclease activity of the UPR sensor inositol-requiring enzyme 1 (IRE-1) and X box binding protein 1 (XBP-1), which alleviate ER stress. The collective results show that chemical UPR induction and viruses boost tumor cell killing by enhancing oncolytic viral efficacy. IMPORTANCE Cancer is difficult to combat. A wide range of oncolytic viruses show promise for killing cancer cells, yet the efficacy of oncolytic killing is low. We searched for host factors enhancing adenovirus cancer cell killing and found that the knockdown of Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF-1) or chemical inhibition of GBF-1 enhanced adenovirus infection by triggering the IRE-1/XBP-1 branch of the unfolded protein response (UPR). IRE-1/XBP-1 promote cell survival and enhanced the levels of the adenoviral immediate early gene product E1A, virus spreading, and killing of cancer cells. Aggressive tumor cells depend on a readily inducible UPR and, hence, present prime targets for a combined strategy involving adenoviruses and small chemicals inducing UPR.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.02156-14
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1495529-5
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  • 6
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    Online Resource
    Distinct role of non-covalent interactions to the function and structural stability of glutaredoxins: a multifunctional redox protein
    Inderscience Publishers ; 2010
    In:  International Journal of Bioinformatics Research and Applications Vol. 6, No. 3 ( 2010), p. 241-
    Details
    In: International Journal of Bioinformatics Research and Applications, Inderscience Publishers, Vol. 6, No. 3 ( 2010), p. 241-
    Type of Medium: Online Resource
    ISSN: 1744-5485 , 1744-5493
    URL: Article
    DOI: 10.1504/IJBRA.2010.034073
    Language: English
    Publisher: Inderscience Publishers
    Publication Date: 2010
    SSG: 12
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  • 7
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    Online Resource
    Modic changes - An evidence-based, narrative review on its patho-physiology, clinical significance and role in chronic low back pain
    Elsevier BV ; 2020
    In:  Journal of Clinical Orthopaedics and Trauma Vol. 11, No. 5 ( 2020-09), p. 761-769
    Details
    In: Journal of Clinical Orthopaedics and Trauma, Elsevier BV, Vol. 11, No. 5 ( 2020-09), p. 761-769
    Type of Medium: Online Resource
    ISSN: 0976-5662
    URL: Article
    DOI: 10.1016/j.jcot.2020.06.025
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2596956-0
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  • 8
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    Management of Soft-tissue Defects of Hand in a Conflict Combat Zone: A Case Series
    Indian Orthopaedic Research Group ; 2023
    In:  Journal of Orthopaedic Case Reports Vol. 13, No. 7 ( 2023), p. 134-139
    Details
    In: Journal of Orthopaedic Case Reports, Indian Orthopaedic Research Group, Vol. 13, No. 7 ( 2023), p. 134-139
    Abstract: Introduction: Managing soft-tissue defects of hand is a challenging problem for any surgical team, even more in a field hospital setting of a conflict combat zone, where resources are scarce and such cases due to blunt trauma, gunshot wound and deep tissue infections are common. Case Report: We present four different cases, all middle aged males, who sustained injuries due to crush, low velocity gun shot, and defects post-debridement of acute onset infections following abrasions. The first patient was managed with doubled pedicled abdominal flap, the second patient was managed with external fixation for fracture, and cross finger flap for the defect. The third and fourth patients had similar presentations of acute onset deep soft tissue and bony infection, out of which one was managed with full thickness skin graft from anterior abdominal wall and the other with bi-pedicled abdominal flap. All the patients had good functional outcomes with no functional restrictions at follow-up of 12 weeks. Conclusion: All the cases were performed in a challenging situation of a highly active combat field zone, with limited resources and lack of availability of a trained hand surgeon. An early soft-tissue coverage, as soon as possible, was crucial in saving the hand function and guaranteeing a speedy return to function in view of lack of a professional hand surgery team and specialized microsurgery equipment. Keywords: Hand defect, UN field hospital, combat zone.
    Type of Medium: Online Resource
    ISSN: 2250-0685 , 2321-3817
    URL: Article
    DOI: 10.13107/jocr.2023.v13.i07.3784
    Language: Unknown
    Publisher: Indian Orthopaedic Research Group
    Publication Date: 2023
    detail.hit.zdb_id: 2658169-3
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  • 9
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    Online Resource
    Multifocal Pediatric Tumoral Calcinosis: a Diagnostic Conundrum in a 4-Year-Old Child
    Springer Science and Business Media LLC ; 2023
    In:  Indian Journal of Surgery
    Details
    In: Indian Journal of Surgery, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0972-2068 , 0973-9793
    URL: Article
    DOI: 10.1007/s12262-023-03829-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2109793-8
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  • 10
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    Online Resource
    Cervical spine TB – Current concepts in management
    SAGE Publications ; 2021
    In:  Journal of Orthopaedic Surgery Vol. 29, No. 1_suppl ( 2021-09-01), p. 230949902110069-
    Details
    In: Journal of Orthopaedic Surgery, SAGE Publications, Vol. 29, No. 1_suppl ( 2021-09-01), p. 230949902110069-
    Abstract: Cervical tubercular disease (CTB) is a rare pathology and constitutes 3–5% of all spinal TB. It includes atlantoaxial TB and sub-axial TB. As the literature evidence on this subject is scarce, majority of issues concerning CTB are still controversial. The current narrative review comprehensively discusses the various aspects related to CTB. Literature search: An elaborate search was made using keywords cervical tuberculosis, atlantoaxial tuberculosis, sub-axial tuberculosis, and cervico-thoracic tuberculosis, on pubmed and google ( scholar.google.com ) databases on 2 December 2020. We identified crucial questions regarding CTB and included relevant articles pertaining to them. Results: The initial search using keywords cervical tuberculosis, atlantoaxial tuberculosis, sub-axial tuberculosis, and cervico-thoracic tuberculosis yielded 4128, 76, 3 and 9 articles on ‘pubmed’ database, respectively. A similar search using the aforementioned keywords yielded 1,96,000, 2130, 117 and 728 articles on ‘google scholar’ database. The initial screening resulted in the identification of 178 articles. Full manuscripts were obtained for these articles and thoroughly scrutinised at the second stage. Review articles, randomised controlled trials and level 1 studies were given preference. Overall, 41 articles were included. Conclusion: AATB and SACTB constitute 0.3 to 1% and 3% of spinal TB, respectively. The incidence of neuro-deficit in CTB is significantly more than other spinal TB. The general principles of management of CTB are similar to spinal TB elsewhere and medical therapy remains the cornerstone. Surgery is advocated in specific scenarios involving gross neuro-deficit, later stages of disease with significant bony/ligamentous disruptions, altered sagittal balance, drug resistance, and poor response to medications. The surgical approaches for AATB include anterior-alone, posterior-alone and combined approaches, although posterior access is the most preferred. Most of the studies on SACTB have supported the role of anterior approach. Additionally, posterior stabilisation may be necessary in specific scenarios. The overall long-term outcome in CTB is favourable.
    Type of Medium: Online Resource
    ISSN: 2309-4990 , 2309-4990
    URL: Article
    DOI: 10.1177/23094990211006936
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2128854-9
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