Chandigarh, India
Chandigarh, India
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OBJECTIVE: To study the role of mid-induction (day 15) peripheral blood minimal residual disease (PB-MRD) detection in pediatric B- lineage acute lymphoblastic leukemia (B-ALL).DESIGN: Prospective.SETTING: Tertiary-care center.PATIENTS: 40 consecutively-diagnosed treatment-naive, pediatric B-ALL patients.INTERVENTION: National Cancer Institute (NCI) standard risk patients were given three drug induction regimen comprising vincristine, L-asparginase and prednisolone; NCI high-risk patients were supplemented with daunorubicin.MAIN OUTCOME MEASURE: Day 15 PB-MRD and bone marrow MRD (BM-MRD) analyzed by six color flow cytometry.RESULTS: The sensitivity of day 15 PB-MRD to identify concurrent day 15 BM-MRD positivity was 64%, with 100% specificity. The positive and negative predictive values were 100% and 62.5%, respectively. PB-MRD was positive in 67% of relapsed patients.CONCLUSION: BM-MRD is a well-established prognostic factor in B-ALL. We suggest, day 15 PB-MRD could be considered as an early, minimally invasive and easily accessible MRD screening option.

Copper (Cu) has been the subject of intensive research over several decades as numerous evidence robustly support the involvement of excess Cu induced neurotoxicity in hepatocerebral (Wilson's disease) and neurodegenerative disorders (especially Alzheimer's disease and Parkinson's disease); notwithstanding, the ideal Cu neurotoxicity biomarker/s for early prognosis remains elusive. Non-ceruloplasmin bound Cu is a biological marker of Wilson's disease and recent studies have shown that its levels are also increased in Alzheimer's disease. Copper chaperone for superoxide dismutase seems to be the other most promising biomarker of Cu toxicity (subject to its validation). Serum/plasma Cu, urine Cu and ceruloplasmin concentrations, most widely used laboratory indicators to diagnose Wilson's disease, are not specific for Cu excess milieu as these are also influenced by age, sex, inflammation and hormonal status. High inter-individual variability, nonexistence of standardized assays and non-specificity limit the use of other cuproenzymes as biomarkers of Cu neurotoxicity. The majority of Cu neurotoxicity biomarker research has focused in plasma/serum where other factors including inflammation, oxidative stress, dietary and environmental factors influence the Cu condition being studied. Proteomics study of cerebrospinal fluid, due to its high specificity and sensitivity represents an alternative approach to study early peripheral Cu neurotoxicity biomarker/s in experimental animals. In addition, network biology, transcriptomics in conjunction with novel in vivo Cu imaging techniques allow us to explore other potential candidates and propose new targets to be studied for chronic Cu neurotoxicity biomarker/s, and for possible therapeutic interventions. © 2013 Elsevier Inc.

Rastogi P.,PGIMER
Indian pediatrics | Year: 2017

Blood sampling in children is a challenging task, and to extract maximum possible information from these 'precious' samples, the modern-day automated hematology analyzers have been aided with much technological advancement. Various novel blood cell parameters are now available to narrow down the differential diagnoses. However, only few of these are available for routine clinical reporting. Knowledge about their interpretation and reference ranges can prove useful in challenging situations.

Abnormalities in the p53 gene are the most common genetic alterations seen in laryngeal carcinoma. No data exist regarding the association between laryngeal carcinoma and a distinct codon 72 variant and its expression. We conducted a prospective study (1) to analyze the p53 codon 72 polymorphic variants in patients with laryngeal carcinoma, (2) to analyze the expression of p53 mRNA in tissues of patients with laryngeal carcinoma using the reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and (3) to detect p53 antibodies in the plasma of patients with laryngeal carcinoma before and after treatment. Tissue and blood samples were taken from 40 patients with laryngeal carcinoma-36 men and 4 women, aged 40 to 65 years (mean: 56)-and 20 age-matched controls with laryngeal conditions other than carcinoma. RT-PCR was used to measure p53 mRNA expression, and PCR-restriction fragment length polymorphism was used to determine p53 polymorphism. In addition, p53 antibodies were detected in plasma by Western blot testing. The 40 patients were treated with either surgery (total laryngectomy or conservation surgery) or radiotherapy. Tissue and blood samples were analyzed before treatment and 4 weeks after treatment. The findings were compared with those of the 20 controls. The results revealed that (1) homozygosity of the Pro72 variant of p53 was present in 26 laryngeal carcinoma patients (65%), (2) heterozygosity for the Pro/Arg genotype was present in 13 patients (32.5%), and (3) the Arg72 variant of the p53 allele was present in 1 patient (2.5%) before treatment. Overexpression of p53 mRNA was found in all patients with laryngeal carcinoma and in none of the controls before treatment; the difference was approximately 3.3 folds higher in the carcinoma group. However, p53 expression was not related to the biologic aggressiveness of these tumors. It is interesting that 4 weeks after definitive therapy, the expression levels of p53 mRNA in the 40 patients were comparable to those of the controls. The p53 antibodies were detected in the plasma of all patients with laryngeal carcinoma prior to definitive therapy and in none of them afterward, indicating that these antibodies represent a prognostic marker in laryngeal carcinoma. Our findings suggest that there is a correlation between p53 overexpression and the development of laryngeal carcinoma. Anti-p53 antibodies can be used as a prognostic marker in laryngeal carcinoma, and they can be exploited in the future to control the response to therapy and to monitor for certain early recurrences before they become clinically detectable.

Neurology India | Year: 2010

Ophthalmoplegic migraine (OM) is a rare disorder characterized by childhood onset, ophthalmoplegia and migraine headaches. The 3rd cranial nerve is commonly involved in recurrent attacks. Involvement of the sixth and fourth nerves is uncommon. GdMRI discloses enhancement of the nerves. Adult cases are rare and confined to case reports. A viral pathogenesis is considered to be the cause of OM in view of nerve enhancement. We look at the various aspects of OM in children and adults.

Journal of Neuroimmune Pharmacology | Year: 2010

Hepatitis C virus (HCV) infection can have devastating long-term sequelae. It is very common in injecting drug users (IDU) worldwide. India has a huge number of substance abusers, with an estimated 1.1 million IDU. Research on HCV prevalence in IDU and especially other substance use is sparse. This review identified 15 such studies. Some of these also studied prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections and co-infection rates. The summary findings indicate that there are pockets of very high HCV seroprevalence (60-90%), otherwise the range is moderate (30-50%), though, in real terms, it still indicates the appreciable magnitude of the problem that may emerge as an epidemic if it goes unheeded. HCV infection seems to be more common in IDU than HBV and HIV infections, again pointing toward the urgent need to prioritise this area. Co-infection rates are low in most of the few studies available, but clearly more studies are needed. There is a glaring paucity of studies on risk behaviours that can be linked meaningfully to HCV infection and its consequences. The urgent future research needs in this important area are highlighted. © 2010 Springer Science+Business Media, LLC.

Bhatia A.,PGIMER | Kumar Y.,PGIMER
Expert Review of Clinical Immunology | Year: 2014

Immune escape is the final phase of cancer immunoediting process wherein cancer modulates our immune system to escape from being destroyed by it. Many cellular and molecular events govern the cancer's evasion of host immune response. The tumor undergoes continuous remodeling at the genetic, epigenetic and metabolic level to acquire resistance to apoptosis. At the same time, it effectively modifies all the components of the host's immunome so as to escape from its antitumor effects. Moreover, it induces accumulation of suppressive cells like Treg and myeloid derived suppressor cells and factors which also enable it to elude the immune system. Recent research in this area helps in defining the role of newer players like miRNAs and exosomes in immune escape. The immunotherapeutic approaches developed to target the escape phase appear quite promising; however, the quest for a perfect therapeutic agent that can achieve maximum cure with minimal toxicity continues. © 2014 Informa UK, Ltd.

Pal A.,P.G.I.M.E.R. | Prasad R.,P.G.I.M.E.R.
Neurotoxicity Research | Year: 2014

In the last two decades, there has been widespread acknowledgment of the pivotal role played by astrocytes in diverse aspects of central nervous system functioning. Astrocytes are crucial for the homeostasis of the copper in the central nervous system as evident by its proficiency in acquisition, trafficking, and export of copper. Moreover, the imbalance in copper homeostasis and impairment in astrocyte functioning are increasingly being recognized as an important contributing factor in the development of neurodegeneration and cognitive waning. In this review, we discuss the most recent advances in the field of copper homeostasis in astrocytes along with briefly outlining the copper dyshomeostasis associated hepatocerebral and neurodegenerative diseases. © 2013 Springer Science+Business Media.

Background: Rheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD. Methods: Endomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Results: Histomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens. Immunohistochemistry: Moderate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8 + cells in 77%, CD4 + in 23.1%, and CD3 + in 38.5% of total patients, which suggests chronicity. Conclusion: The nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself. © 2012 Elsevier Inc. All rights reserved.

Bhatia A.,PGIMER | Kumar Y.,PGIMER
APMIS | Year: 2013

Micronucleus (MN) is the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. Any form of genotoxic stress due to extraneous or internal factors leads to formation of a MN, which serves as an indicator of chromosomal instability. Chromosomal damage and formation of MN are believed to play a significant role in the pathogenesis of many malignancies. Studies have shown that MN assay can be used as a tool for risk prediction, screening, diagnosis, prognosis and as a treatment-response indicator in cancers. With the advancements in technology, greater details are becoming available regarding the molecular events in carcinogenesis. The micronuclei (MNi) in the cancer cells are now being used as tools to understand the pathogenetics of the malignancies. However, despite large number of studies on MNi in lymphocytes or exfoliated cells of cancer patients, the data regarding a cancer cell MN remain scarce. This review article tries to unleash some of the mysteries related to the formation of MN inside the cancer cell. Also, it discusses the possible effects and the events post MN formation in the cancer cell. © 2012 APMIS. Published by John Wiley & Sons Ltd.

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