Publications by authors named "Pallavi Gaikwad"

7 Publications

  • Page 1 of 1

The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India.

Front Immunol 2021 5;12:612583. Epub 2021 Mar 5.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in , and genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in , and genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.
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http://dx.doi.org/10.3389/fimmu.2021.612583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973116PMC
March 2021

Clinical and Genetic Spectrum of a Large Cohort of Patients With Leukocyte Adhesion Deficiency Type 1 and 3: A Multicentric Study From India.

Front Immunol 2020 16;11:612703. Epub 2020 Dec 16.

Department of pediatric, Indira Gandhi Institute of Child Health, Bangalore, India.

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 gene. LAD type 2 (LAD2) is caused by mutations in the 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 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 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 gene, and 4 novel mutations were detected in the 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.
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http://dx.doi.org/10.3389/fimmu.2020.612703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772426PMC
December 2020

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

Biochem Biophys Res Commun 2016 Aug 26;476(4):371-378. Epub 2016 May 26.

Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007, India. Electronic address:

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study.
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http://dx.doi.org/10.1016/j.bbrc.2016.05.129DOI Listing
August 2016

Unfolding and inactivation of proteins by counterions in protein-nanoparticles interaction.

Colloids Surf B Biointerfaces 2016 Sep 2;145:194-200. Epub 2016 May 2.

Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai 400085, India. Electronic address:

In this work, the structure and activity of proteins; such as, hen egg lysozyme (HEWL) and calf intestine alkaline phosphatase (CIAP); have been investigated after incubation with surface coated iron oxide nanoparticles (IONPs) in water. IONPs were coated with counterions bound charge-ligands and were named as the charge-ligand counterions iron oxide nanoparticles (CLC-IONPs). The coating was done with tri-lithium citrate (TLC) and tri-potassium citrate (TKC) to have negative surface charge of CLC-IONPs and Li(+) and K(+), respectively, as counterions. To have positive surface charge, IONPs were coated with cetylpyridinium chloride (CPC) and cetylpyridinium iodide (CPI) having Cl(-) and I(-), respectively, as counterions. The secondary structure of proteins was measured using far ultraviolet circular dichroism (CD) spectroscopy which showed that both proteins were irreversibly unfolded after incubation with CLC-IONPs. The unfolded proteins were seen to be functionally inactive, as confirmed through their activity assays, i.e., HEWL with Escherichia coli (E. coli) and CIAP with para-nitrophenyl phosphate (pNPP). Additionally, we have observed that monomeric hemoglobin (Hb) from radio-resistant insect Chironomus ramosus (ChHb) was also partially unfolded upon interaction with CLC-IONPs. This work clearly shows the role of counterions in protein inactivation via protein-nanoparticles interaction and, therefore, CLC-IONPs could be used for therapeutic purpose.
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http://dx.doi.org/10.1016/j.colsurfb.2016.04.053DOI Listing
September 2016

The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.

J Hazard Mater 2016 Apr 29;307:281-93. Epub 2015 Dec 29.

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity.
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http://dx.doi.org/10.1016/j.jhazmat.2015.12.029DOI Listing
April 2016

Chironomus ramosus larvae exhibit DNA damage control in response to gamma radiation.

Int J Radiat Biol 2015 16;91(9):742-8. Epub 2015 Sep 16.

a Department of Zoology , Savitribai Phule Pune University , Pune , India.

Purpose: Chironomus ramosus is one of the recently reported radiotolerant insects. Salivary gland cells of fourth instar larvae respond to ionizing radiations with increases in the levels of antioxidant enzymes and chaperone proteins. Here we made an attempt to study the state of nuclear DNA after exposure of larvae to a lethal dose for 20% of the population (LD(20)) of gamma radiation (2200 Gy, at a dose rate 5.5 Gy/min).

Materials And Methods: Genomic DNA preparations were subjected to competitive ELISA (Enzyme linked immunosorbent assay) for detection of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and dynamic light scattering (DLS) to monitor any radiation-induced damage. Single salivary gland cells were subjected to alkaline single cell gel electrophoresis (ASCGE), comet assay and pulsed field gel electrophoresis (PFGE) to check for DNA double-strand breaks.

Results: Results from all four experimental procedures confirmed damage of nucleobases and fragmentation of nuclear DNA immediately after radiation. Some 48 h after radiation exposure, modified 8-oxodG residues returned to basal level, homodispersity of genomic DNA reappeared, the length of comet tail regressed significantly (ASCGE) and PFGE pattern matched with that of high molecular weight unirradiated DNA.

Conclusion: Chironomus ramosus larvae showed control of DNA damage as observed over 48 h in post irradiation recovery which could be attributed to their ability to tolerate gamma radiation stress.
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http://dx.doi.org/10.3109/09553002.2015.1062572DOI Listing
April 2016

The direct way of indirect bonding--the combined effect.

Int J Orthod Milwaukee 2013 ;24(3):15-7

ACPM Dental College, Dhule Maharashtra, India.

The placement of orthodontic bonded brackets may be accomplished by either a direct or indirect technique. Most orthodontists will agree that brackets can be positioned more accurately on study casts than directly on teeth in the mouth. And, also direct bonding is more demanding to the orthodontist. Yet, very few orthodontists routinely use an indirect bonding technique. The reasons commonly given for not using the indirect method are difficulty in achieving consistent and predictable adhesion to the teeth, excess of composite around the bracket margins, failure to get all the brackets to adhere to the teeth e the expense of the materials. These disadvantages can be overcome by a new simplified method of bonding outlined in this article; additionally it has advantages of direct bonding also.
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February 2014