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Nirmal Kumar

Publications and source records attributed to Nirmal Kumar.

16 recordsLinked to original sources
PubMed2025

Monitoring Influenza A Virus Entry Using Quantitative Fluorescence Microscopy.

Influenza A virus (IAV) is a major threat to global human health and is a topic of intense research. With the continuous problem of seasonal influenza and the threat of potential pandemics due to frequent emergence of new viral strains, development of new, broad-spectrum antivirals is an urgent priority. In antiviral development against influenza, the process of host cell entry of IAV is of particular interest as inhibiting the virus at the entry step should stop infection early on, blocking the downstream infection processes including viral replication and transcription. Therefore, a detailed understanding of the IAV entry processes is essential to illuminate virus-assisting host factors that can serve as potentially valuable targets for therapeutic interventions. To accelerate the identification of novel antivirals or host-directed targets that play essential role in IAV entry, quantitative assays that can be used to monitor the virus at sequential entry steps would be important for performing high-content genetic or inhibitor screens. In this chapter, we describe how IAV entry can be monitored at the sequential entry steps, spanning from the initial attachment of the virus particle to the cell surface to the transmission of the viral genome to the nucleus, by fluorescence microscopy. Further, we provide the methods to quantify the images acquired with high-content microscope for each of the major IAV entry steps. The fluorescence microscopy-based IAV entry assays and the image quantification methods described here can be used to boost our understanding of the virus-host cell interactions and can lead to the discovery of novel host-directed prophylactic or therapeutic interventions.

Humans↗
PubMed2006

Lectindb: a plant lectin database.

Lectins, a class of carbohydrate-binding proteins, are now widely recognized to play a range of crucial roles in many cell-cell recognition events triggering several important cellular processes. They encompass different members that are diverse in their sequences, structures, binding site architectures, quaternary structures, carbohydrate affinities, and specificities as well as their larger biological roles and potential applications. It is not surprising, therefore, that the vast amount of experimental data on lectins available in the literature is so diverse, that it becomes difficult and time consuming, if not impossible to comprehend the advances in various areas and obtain the maximum benefit. To achieve an effective use of all the data toward understanding the function and their possible applications, an organization of these seemingly independent data into a common framework is essential. An integrated knowledge base ( Lectindb, http://nscdb.bic.physics.iisc.ernet.in ) together with appropriate analytical tools has therefore been developed initially for plant lectins by collating and integrating diverse data. The database has been implemented using MySQL on a Linux platform and web-enabled using PERL-CGI and Java tools. Data for each lectin pertain to taxonomic, biochemical, domain architecture, molecular sequence, and structural details as well as carbohydrate and hence blood group specificities. Extensive links have also been provided for relevant bioinformatics resources and analytical tools. Availability of diverse data integrated into a common framework is expected to be of high value not only for basic studies in lectin biology but also for basic studies in pursuing several applications in biotechnology, immunology, and clinical practice, using these molecules.

Algorithms↗
PubMed2006

Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli global regulation.

The role of nonlinear DNA in replication, recombination, and transcription has become evident in recent years. Although several studies have predicted and characterized regulatory elements at the sequence level, very few have investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4 DNA motifs as a model, we have researched the role of DNA structure in transcription on a genome-wide scale. Analyses of >61,000 open reading frames (ORFs) across 18 prokaryotes show enrichment of G4 motifs in regulatory regions and indicate its predominance within promoters of genes pertaining to transcription, secondary metabolite biosynthesis, and signal transduction. Based on this, we predict that G4 DNA may present regulatory signals. This is supported by conserved G4 motifs in promoters of orthologous genes across phylogenetically distant organisms. We hypothesized a regulatory role of G4 DNA during supercoiling stress, when duplex destabilization may result in G4 formation. This is in line with our observations from target site analysis for 55 DNA-binding proteins in Escherichia coli, which reveals significant (P<0.001) association of G4 motifs with target sites of global regulators FIS and Lrp and the sigma factor RpoD (sigma70). These factors together control >1000 genes in the early growth phase and are believed to be induced by supercoiled DNA. We also predict G4 motif-induced supercoiling sensitivity for >30 operons in E. coli, and our findings implicate G4 DNA in DNA-topology-mediated global gene regulation in E. coli.

Conserved Sequence↗
PubMed2005

Tracheal agenesis: two case reports.

Tracheal agenesis is a rare and uniformly lethal congenital malformation. It presents with severe respiratory distress at birth. In this anomaly there is a congenital absence of the trachea and the bronchus communicates with the esophagus. The diagnosis should be suspected in newborn infant with respiratory distress whose intubation is impossible. This report describes our experience in two such cases.

Fatal Outcome↗
PubMed2005

Prone versus supine position in mechanically ventilated children: a pilot study.

BACKGROUND: It is known that mechanically ventilated patients in the prone position have improved oxygenation compared with those supine. We did a prospective, randomized, controlled trial to evaluate the effect of prone position during mechanical ventilation, on survival in critically ill children. MATERIAL/METHODS: Forty-two children needing mechanical ventilation for various illnesses were randomized to receive initial ventilation for four hours prone or supine by drawing lots. Initial severity of illness and blood gases in all children were noted. In a crossover design, after the initial four hours the children were turned over and ventilated in the alternate posture for an hour. Oxygenation parameters and mean airway pressures were noted at one hour, four hours, and five hours. Mortality, duration of ventilation, and the above parameters were compared in the two groups. RESULTS: Initial PRISM scores were similar in the two groups. Mortality in the prone group was less than in the supine group. The odds ratio of mortality was 0.20 (95% CI 0.05-0.75). Duration of ventilation was similar in the two groups. The oxygenation index was significantly lower in the prone group at one, four, and five hours after onset of ventilation. CONCLUSIONS: Prone position in the first few hours of ventilation significantly improves gas exchange and oxygenation, reduces the mean airway pressures required to ventilate children, and may cause significant improvement in survival. Our study protocol allowed ventilator settings to be changed as needed during ventilation.

Child, Preschool↗
PubMed2005

p53 gene mutation and human papillomavirus (HPV) infection in esophageal carcinoma from three different endemic geographic regions of India.

Infection of high-risk human papillomaviruses (HPVs), particularly the HPV types 16 and 18 and mutation or aberrant expression of the p53 tumour suppressor gene, has strongly been implicated in human esophageal carcinoma, which shows a great variation in geographic distribution. Neither the reason(s) for such a variation nor the etiopathogenesis of the disease is clearly understood. The present study has been carried out to determine prevalence of high-risk HPV types 16 and 18 and the p53 gene mutation in patients from three distinctly different endemic geographic regions of India, viz. Kashmir, Dibrugarh, and New Delhi where esophageal cancer is most prevalent. The people from each of these regions differ considerably in their food, drinking, smoking and chewing habits (tobacco and betel nut) and ethnic background. While PCR was employed to detect high-risk HPV types 16 and 18 DNA sequences, PCR-SSCP and direct nucleotide sequencing was used for analysis of p53 mutation. Out of a total of 101 biopsy specimens of carcinoma esophagus analysed, the frequency of HPV was found to be the highest 14/32 (44%) in Dibrugarh followed by 33% (11/33) in Kashmir, but, interestingly, no high-risk HPV could be detected in New Delhi patients who showed the highest frequency (30.6%) of p53 mutation as against only 12.5% in Dibrugarh and 6.1% in Kashmir. The difference in the frequency of p53 mutation between the three regions was statistically highly significant (0.018). Out of a total of 21 nucleotide alterations observed, 12 missense, five frameshift and four were silent changes. The p53 exon 7 appears to be the 'hot-spot' for esophageal cancer as it alone was responsible for more than 76% (13/17) of mutations and more than 95% (20/21) of the patients with p53 mutation were smokers. The results demonstrate differential distribution of HPV infection and p53 mutation in esophageal cancer from different geographic regions of India and this could be due to variation in diet, drinking, and tobacco habit, including ethnic, socio-cultural and genetic variation.

Adult↗
PubMed2003

Long QT syndrome manifesting as pulseless epilepsy.

A-10-year-old child admitted with repeated seizures due to the long QT syndrome is described. The cardiac origin of the epilepsy was suggested by the fact that during the episode of convulsions his peripheral pulses were not palpable.

Adrenergic beta-Antagonists↗
PubMed2002

The clinical risk index of babies (CRIB) score in India.

OBJECTIVE: To assess the usefulness of clinical risk index of babies (CRIB score) in predicting neonatal mortality in extremely preterm neonates, compared to birth weight and gestation. METHODS: 97 preterm neonates with gestational age less than 31 weeks or birth weight less than or equal to 1500 g were enrolled for the prospective longitudinal study. Relevant neonatal data was recorded. Blood gas analysis results and the maximum and the minimum FiO2 required by babies in first 12 hours of life were noted. Mortality was taken as death while the baby was in nursery. The prediction of mortality by birth weight, gestational age and CRIB score was done using the Logistic model, and expressed as area under the ROC curve. RESULTS: The area under the ROC curve for birth weight, gestational age and CRIB score was almost the same, the areas being 0.829, 0.819 and 0.823 respectively. Hence CRIB score did not fare better than birth weight and gestational age in predicting neonatal mortality. CONCLUSION: The CRIB score did not improve on the ability of birth weight and gestational age to predict neonatal mortality in the study.

Gestational Age↗
PubMedDate not supplied

Surgical management of obstructive gastroduodenal tuberculosis.

BACKGROUND: Gastroduodenal tuberculosis is a rare but potentially curable condition. The aim of the present study was to evaluate the clinical presentation, pre-operative status, management and outcome in patients with histologically proven diagnosis of gastroduodenal obstruction due to tuberculosis. METHODS: We retrospectively reviewed the records of 17 patients managed surgically for gastroduodenal obstruction due to tuberculosis. RESULTS: The site of obstruction was the pyloroduodenal canal in 53% of patients, second part of the duodenum in 24%, third part of the duodenum in 12% and duodenjojejunal flexure in 12%. The obstruction was caused by fibrotic stricture formation in 59% of patients and extrinsic compression by a lymph nodal mass in 41%. Endoscopic biopsy was diagnostic in only 29% of the patients in whom it was performed. Overall, a pre-operative diagnosis of gastroduodenal tuberculosis was suspected in only 35% of patients. All the patients underwent surgical drainage procedures and the diagnosis was confirmed by histopathological examination of biopsies taken at the time of laparotomy. CONCLUSIONS: In view of its rarity and non-specific findings on clinical, radiological and endoscopic evaluation, tuberculosis as a cause of gastroduodenal obstruction is seldom diagnosed pre-operatively. Hence, a high index of suspicion is required in young patients residing in endemic areas. Surgical intervention helps not only in relieving obstruction but also in confirming the diagnosis.

Adolescent↗
PubMedDate not supplied

Isolated tuberculosis of the pancreas: a report of two cases and review of the literature.

We report two cases of pancreatic tuberculosis. The first patent (who tested positive for HIV) presented with abdominal pain, fever, weight loss, anorexia and tender epigastric lump. The CT scan revealed multiple small abscesses in the pancreas. The second patients, who had no evidence of immunodeficiency, presented with constitutional symptoms and obstructive jaundice. The CT scan revealed a mass in the pancreatic head with peripancreatic lymph nodes and dilatation of the intrahepatic and extrahepatic biliary tree. None of the patients had Mycobacterium tuberculosis infection of the lung or any other organ. Fine-needle aspiration biopsy clinched the diagnosis in both the patients, with caseation necrosis and plenty of acid-fast bacilli in the first patient, and characteristic granulomatous inflammation of the pancreas in the other. The first patient died during the index hospitalization, while the other responded well to antitubercular treatment with improvement in symptoms and radiological clearance of the initial lesions.

Adult↗
PubMedDate not supplied

Colour Doppler flow imaging findings in portal biliopathy.

Biliary abnormalities in extrahepatic portal vein obstruction (EHPVO) have been described in detail on endoscopic retrograde cholangiopancreaticography (ERCP), but have never before been reported on colour Doppler flow imaging (CDFI). These changes occur either due to extrinsic compression of the bile ducts or due to ischaemic biliary stenosis. The aim of this study was to evaluate the role of CDFI in demonstrating the biliary changes in patients with EHPVO. Three out of 46 patients with EHPVO (7%), who presented clinically with obstructive jaundice, were subjected to a detailed CDFI study of the abdomen, followed by ERCP and splenoportovenography (SPV). One of the patients also underwent a repeat CDFI examination at 8 weeks following a lienorenal shunt. In all 3 cases, CDFI easily distinguished the anechoeic structures seen on ultrasound at the porta hepatis as periportal collaterals, the hepatic artery and dilated bile ducts. It revealed the actual indentation made on the common bile duct (CBD) by the collaterals besides showing the presence of biliary calculi. Gallbladder varices were also well demonstrated in all the cases. ERCP confirmed the presence of portal biliopathy besides showing other changes, such as angulation, displacement and stricture of the CBD. SPV confirmed the presence of EHPVO. One patient who underwent shunt surgery showed persistent dilatation of the CBD with calculi. CDFI is a rapid, non-invasive and widely available modality which can be used to demonstrate the biliary changes in patients with EHPVO with obstructive jaundice. It may thus help screen patients who require a further by ERCP examination for the planning of treatment.

Bile Duct Diseases↗
PubMedDate not supplied

Vascular tethering of the megaoesophagus by the azygos arch masquerading as a malignancy.

We report the case of a 50-year-old male, a known case of achalasia cardia for 15 years, who after being successfully treated earlier by pneumatic dilatation, presented with recurrent dysphagia due to vascular tethering of the megaoesophagus by the azygos arch simulating a malignant oesophageal stricture. The patient underwent oesophagectomy because of our inability to rule out the possibility of a malignancy developing in the mid-portion of the long-standing megaoesophagus. We wish to highlight the existence of this new clinical entity and the diagnostic as well as therapeutic dilemmas posed by it.

Azygos Vein↗
PubMedDate not supplied

Superimposed acute hepatitis E infection in patients with chronic liver disease.

BACKGROUND: The natural history of infection with hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is not well described. Our study aims to document the presentation, course and outcome of HEV superinfection in patients with CLD. METHODS: Over an 18-month period, ten patients with CLD were diagnosed to have HEV superinfection by detection of anti-HEV IgM antibodies in a setting of acute worsening. These patients were tested for HBsAg, IgM anti-HBc, anti-hepatitis C virus antibodies and IgM anti-hepatitis A virus antibodies, and were followed-up. RESULTS: The etiology of underlying CLD in the 10 patients (9 men; mean [SD] age 42.4 [10.3] years) was alcohol in five patients, hepatitis B in two, hepatitis C in one and cryptogenic in two. Seven patients presented for the first time with recent-onset liver decompensation (median duration 27 days, range 7-45). All 10 had ascites and 7 had hepatic encephalopathy. Four patients developed renal failure during the course of illness. The median (range) bilirubin, ALT and albumin levels at presentation were 18.6 (4.9-32.6) mg/dL, 105 (28-6610) IU/L and 32 (29-41) g/L, respectively. At 8 weeks, only one patient had normalization of serum bilirubin or ALT levels. Three patients (30%) died, including two of renal failure and one of massive upper GI bleed. CONCLUSIONS: Superinfection with HEV in patients with CLD causes severe liver decompensation, which is frequently complicated with hepatic encephalopathy and renal failure. Acute hepatitis E in these patients has a protracted course with high morbidity and mortality.

Adult↗