Biomedical subjects

Anita Pandit

Publications and source records attributed to Anita Pandit.

4 recordsLinked to original sources

PubMed2023

The phenotype-genotype reference map: Improving biobank data science through replication.

Population-scale biobanks linked to electronic health record data provide vast opportunities to extend our knowledge of human genetics and discover new phenotype-genotype associations. Given their dense phenotype data, biobanks can also facilitate replication studies on a phenome-wide scale. Here, we introduce the phenotype-genotype reference map (PGRM), a set of 5,879 genetic associations from 523 GWAS publications that can be used for high-throughput replication experiments. PGRM phenotypes are standardized as phecodes, ensuring interoperability between biobanks. We applied the PGRM to five ancestry-specific cohorts from four independent biobanks and found evidence of robust replications across a wide array of phenotypes. We show how the PGRM can be used to detect data corruption and to empirically assess parameters for phenome-wide studies. Finally, we use the PGRM to explore factors associated with replicability of GWAS results.

Humans↗

PubMed2005

Is there a difference between chronic airway inflammation in chronic severe asthma and chronic obstructive pulmonary disease?

PURPOSE OF REVIEW: The lack of a universally accepted definition of chronic severe asthma and the continuous changes in the classification of the severity of stable chronic obstructive pulmonary disease in the last 10 years make it difficult to compare the many studies available. The aim of the review is to compare studies on chronic severe asthma that have a control group of patients with mild to moderate persistent asthma and studies on stable chronic obstructive pulmonary disease that have an age-matched control group of smokers with normal lung function (with or without chronic bronchitis). RECENT FINDINGS: Our review of the recent literature in this field seems to indicate that chronic airway inflammation in chronic severe asthma is characterized in most cases, both in central and peripheral airways, by the same pathological features of mild-moderate persistent asthma with an increased number of activated T lymphocytes, particularly CD4 Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate disease is the increased number of neutrophils. Chronic airway inflammation in stable chronic obstructive pulmonary disease is characterized, both in central and peripheral airways, by an increased number of T lymphocytes, particularly CD8+, macrophages and neutrophils. Macrophage and neutrophil counts increase with the progression of the severity of the disease. SUMMARY: These differences in chronic airway inflammation support the consensus that asthma and chronic obstructive pulmonary disease are different diseases along all their stages of severity.

Asthma↗

PubMed2004

Characterization of ciliated bronchial epithelium 1, a ciliated cell-associated gene induced during mucociliary differentiation.

Lung epithelial structure is altered in asthma; however, the precise mechanisms underlying epithelial repair, including differentiation from basal to columnar epithelial cells, are not well defined. In the course of random sequencing of a cDNA library from human lung biopsies, we have identified a novel gene, ciliated bronchial epithelium 1 (CBE1). Expression of CBE1 was induced during in vitro differentiation of bronchial epithelial cells. Synchronous expression with tektin and hepatocyte nuclear factor 3/forkhead homologue 4, down-regulation by interleukin-13, and its tissue distribution strongly suggested that CBE1 is associated with ciliated cells. Two isoforms of the 0.7-kb full-length cDNA were identified, resulting in open reading frames with different carboxyl termini, with no homology to known proteins. Expression of CBE1 in ciliated epithelial cells was confirmed by immunohistochemistry. Quantitative reverse transcription-polymerase chain reaction analysis using bronchial biopsies showed no difference of expression of CBE1 between normal subjects and subjects with asthma. Expression studies showed that CBE1 is nuclear- or perinuclear-localized, depending on cell type. Regulated expression during differentiation and the subcellular localization of CBE1 suggest that it may play an important role in the differentiation and/or function of ciliated cells in human airways.

Amino Acid Sequence↗

PubMed2002

Analysis of novel disease-related genes in bronchial asthma.

Bronchial asthma is a complex disease characterized by airway inflammation involving interleukin (IL)-4 and IL-13. We have applied microarray analyses to human bronchial epithelial cultures to probe for genes regulated by these cytokines and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, showed the highest expression by IL-4 and IL-13, and particularly, SCCA1 was significantly increased in the asthmatic cDNA library. STAT6 was shown to be involved in expression of SCCA1 and SCCA2 in vitro. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchia asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation.

Adolescent↗