Biomedical subjects

Anu Sharma

Publications and source records attributed to Anu Sharma.

12 recordsLinked to original sources

PubMed2005

Assessing natural variations in gene expression in humans by comparing with monozygotic twins using microarrays.

Quantitative variation in gene expression in humans is the outcome of various factors, including differences in genetic background, gender, age, and environment. However, the extent of the influence of these factors on gene expression is not clear. We attempted to address this issue by carrying out gene expression profiling in blood leukocytes with 13 individuals (including 5 pairs of monozygotic twins) on 10,000 genes using HG-U95Av2 oligonucleotide microarrays. The proportion of differentially expressed genes between monozygotic twins was low (up to 1.76%). Most of the variations belonged to the least variable category. These genes, exhibiting "random variations," did not show clear preference to any functional class, although "signaling and communication" and "immune and related functions" generally topped the list. The extent of variation in gene expression increased in comparisons between unrelated individuals (up to 14.13%). Most of the genes (89%) exhibiting random variations in twins also varied in expression in unrelated individuals. As with twins, signaling and communication topped the list, and substantial variations were observed in all three categories: least variable, moderately variable, and most variable. An important outcome of this study was that the housekeeping genes were nearly insensitive to random variations but appeared to be more susceptible to genetic differences. However, the highly expressed housekeeping genes exhibited low variation and appeared to be insensitive to all known factors. Gene expression profiling in monozygotic twins can provide useful data for the assessment of natural variation in gene expression in humans.

Adult↗

PubMed2005

Developmental changes in refractoriness of the cortical auditory evoked potential.

OBJECTIVE: This study examined morphological changes in the cortical auditory evoked potential (CAEP) waveform as a function of varying stimulation rate. Stimuli were presented in a paradigm which indirectly assesses the refractory properties of the underlying neuronal generators. METHODS: CAEPs were recorded in 50 normal-hearing children (3-12 years) and 10 young adults (24-26 years). A speech sound was presented in a stimulus train with sequentially decreasing inter-stimulus intervals (ISIs) of 2000, 1000, 560, and 360ms. Latencies and amplitudes of the P1, N1, and P2 components at the Cz electrode were examined as a function of stimulus rate and age. RESULTS: Results revealed significant changes in the CAEP as a function of age and stimulation rate. At younger ages the N1-P2 component was elicited only at the slowest stimulation rates, and was more clearly apparent at successively faster stimulation rates as age increased. CONCLUSIONS: We have described a stimulus paradigm that allows examination of the development of refractoriness by highlighting the interaction between age and rate on CAEP morphology. SIGNIFICANCE: Complex maturational patterns of CAEP components are best understood when the effects of both age and stimulus rate on the CAEP waveform are considered.

Acoustic Stimulation↗

PubMed2005

The influence of a sensitive period on central auditory development in children with unilateral and bilateral cochlear implants.

We examined the longitudinal development of the cortical auditory evoked potential (CAEP) in 21 children who were fitted with unilateral cochlear implants and in two children who were fitted with bilateral cochlear implants either before age 3.5 years or after age 7 years. The age cut-offs (<3.5 years for early-implanted and >7 years for late-implanted) were based on the sensitive period for central auditory development described in [Ear Hear. 23 (6), 532.] Our results showed a fundamentally different pattern of development of CAEP morphology and P1 cortical response latency for early- and late-implanted children. Early-implanted children and one child who received bilateral implants by age 3.5 years showed rapid development in CAEP waveform morphology and P1 latency. Late-implanted children showed aberrant waveform morphology and significantly slower decreases in P1 latency postimplantation. In the case of a child who received his first implant by age 3.5 years and his second implant after age 7 years, CAEP responses elicited by the second implant were similar to late-implanted children. Our results are consistent with animal models of central auditory development after implantation and confirm the presence of a relatively brief sensitive period for central auditory development in young children.

Acoustic Stimulation↗

PubMed2004

ArrayD: a general purpose software for microarray design.

BACKGROUND: Microarray is a high-throughput technology to study expression of thousands of genes in parallel. A critical aspect of microarray production is the design aimed at space optimization while maximizing the number of gene probes and their replicates to be spotted. RESULTS: We have developed a software called 'ArrayD' that offers various alternative design solutions for an array given a set of user requirements. The user feeds the following inputs: type of source plates to be used, number of gene probes to be printed, number of replicates and number of pins to be used for printing. The solutions are stored in a text file. The choice of a design solution to be used will be governed by the spotting chemistry to be used and the accuracy of the robot. CONCLUSIONS: ArrayD is a software for standard cartesian robots. The software aids users in preparing a judicious and elegant design. ArrayD is universally applicable and is available at http://www.igib.res.in/scientists/arrayd/arrayd.html.

Computational Biology↗

PubMed2004

Central auditory maturation and babbling development in infants with cochlear implants.

OBJECTIVE: To examine the relationship between the maturation of central auditory pathways and the development of canonical (speechlike) babbling in infants with cochlear implants. DESIGN: Comparison of the latencies of the P1 cortical auditory evoked potential and vocalizations produced by subjects before they were fitted with a cochlear implant and at several time points within the first year after implantation. SUBJECTS: Two congenitally deaf children who were implanted with a multichannel cochlear implant at ages 13 and 14 months. INTERVENTIONS: P1 response latencies were recorded in response to a /ba/ stimulus before implantation and at several time points following implantation. Vocalizations produced by the subjects while interacting with their caregiver were audiorecorded twice before implantation and at monthly sessions following implantation. RESULTS: Subjects showed a rapid decrease in P1 latencies resulting in normal P1 latencies within about 3 months after implantation. Before implantation, the vocalizations were primarily of a precanonical nature. After 3 months' experience with the implants, the proportion of canonical vocalizations increased dramatically relative to the number of precanonical utterances. CONCLUSIONS: Results of this study suggest that the development of P1 response latencies and the development of early communicative behaviors may follow a similar developmental trajectory in children implanted early. Although preliminary, these findings indicate that the development of early communicative behaviors following implantation may be positively influenced by the rate of plastic changes in central auditory pathways.

Auditory Pathways↗

PubMed2004

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Breast Neoplasms↗

PubMed2003

(TG:CA)(n) repeats in human housekeeping genes.

The unravelling of human genome sequence gives a new opportunity to investigate the role of repetitive sequences in gene regulation. Among the various types of repetitive sequences, the dinucleotide (TG:CA)(n) repeats are one of the most abundant in human genome and exhibit polymorphism. Early on, it was observed that the (TG:CA)(n) repeats could modulate gene expression and has the propensity to undergo conformational transitions in in vivo conditions. Recent reports describe the role of polymorphic (TG:CA)(n) repeats in gene regulation in several genes. In this work, we have analysed the distribution of (TG:CA)(n) (n >or= 6) repeats in human 'housekeeping genes' on which recently released Gene Chip data is available. Our results indicate that (i). The number of short intragenic (TG:CA)(n) repeats is significantly higher than the number of long repeats (ii). the proportion of genes with (TG:CA)(n) repeats (n >or= 12 units) had lower mean expression levels compared to those without these repeats, (iii). the genes belonging to the functional class of 'signalling and communication' had a positive association with repeats in contrast to the genes belonging to the 'information' class that were negatively associated with repeats.

Base Composition↗

PubMed2002

Rapid development of cortical auditory evoked potentials after early cochlear implantation.

The aim of our research was to estimate the time course of development and plasticity of the human central auditory pathways following cochlear implantation. We recorded cortical auditory-evoked potentials in 3-year-old congenitally deaf children after they were fitted with cochlear implants. Immediately after implantation cortical response latencies resembled those of normal-hearing newborns. Over the next few months, the cortical evoked responses showed rapid changes in morphology and latency that resulted in age-appropriate latencies by 8 months after implantation. Overall, the development of cortical response latencies for the implanted children was more rapid than for their normal-hearing age-matched peers. Our results demonstrate a high degree of central auditory system plasticity during early human development.

Analysis of Variance↗

PubMed2002

Lead poisoning among pregnant women in New York City: risk factors and screening practices.

This article presents information on pregnant women with incident blood lead levels (BLLs) of 20 microg per deciliter or greater as reported to the New York City Department of Health between September 1996 and June 1999 (n = 33). Almost half of the women were diagnosed during their third trimester of pregnancy, often at their first prenatal visit. The median BLLs at incidence and at last report among women who were retested were 25 and 15 gamma/dL, respectively, a 40% decline. The median incident BLL among newborns (n = 25) was 12 microg/dL. The BLLs were inversely associated with maternal age and length of time in the United States and directly associated with gestational age and pica behavior. Cases were more than twice as likely to be foreign-born women than all women who gave birth in New York City. Prenatal care facilities employing a policy of universal blood lead testing of all pregnant women at the time of their first visit reported disproportionate numbers of cases, accounting for 77% of cases yet only 11% of all births citywide. The findings suggest that (1) the promulgation of recent rules and guidelines for lead risk assessment and screening among pregnant women appears to have been effective in identifying cases that might not have otherwise come to light; (2) case management and environmental interventions were initiated promptly; (3) cases experienced, on average, significant BLL reductions over time; and (4) there is a need for additional public health interventions for pregnant women in urban, multicultural centers. While the data suggest that universal screening may increase case finding among high-risk, immigrant populations, further studies and surveillance are needed to determine systematically the most effective approach.

Adult↗

PubMed2002

A sensitive period for the development of the central auditory system in children with cochlear implants: implications for age of implantation.

OBJECTIVE: The aim of the present experiment was to assess the consequences of cochlear implantation at different ages on the development of the human central auditory system. DESIGN: Our measure of the maturity of central auditory pathways was the latency of the P1 cortical auditory evoked potential. Because P1 latencies vary as a function of chronological age, they can be used to infer the maturational status of auditory pathways in congenitally deafened children who regain hearing after being fit with a cochlear implant. We examined the development of P1 response latencies in 104 congenitally deaf children who had been fit with cochlear implants at ages ranging from 1.3 yr to 17.5 yr and three congenitally deaf adults. The independent variable was the duration of deafness before cochlear implantation. The dependent variable was the latency of the P1 cortical auditory evoked potential. RESULTS: A comparison of P1 latencies in implanted children with those of age-matched normal-hearing peers revealed that implanted children with the longest period of auditory deprivation before implantation-7 or more yr-had abnormal cortical response latencies to speech. Implanted children with the shortest period of auditory deprivation-approximately 3.5 yr or less-evidenced age-appropriate latency responses within 6 mo after the onset of electrical stimulation. CONCLUSIONS: Our data suggest that in the absence of normal stimulation there is a sensitive period of about 3.5 yr during which the human central auditory system remains maximally plastic. Plasticity remains in some, but not all children until approximately age 7. After age 7, plasticity is greatly reduced. These data may be relevant to the issue of when best to place a cochlear implant in a congenitally deaf child.

Adolescent↗

PubMed2002

Early cochlear implantation in children allows normal development of central auditory pathways.

The goal of this study was to determine whether there is a sensitive period during early development when a cochlear implantation can occur into a minimally degenerate and/or highly plastic central auditory system. Our measure of central auditory deprivation was latency of the P1 auditory evoked potential, whose generators include auditory thalamocortical areas. Auditory evoked potentials were recorded in 18 congenitally deaf children who were fitted with cochlear implants by 3.5 years of age. The P1 latencies of the children with implants were compared with the P1 latencies of their age-matched peers with normal hearing. There was no significant difference between the P1 latencies of the children with implants and the children with normal hearing. The present results suggest that early implantation occurs in a central auditory system that is minimally degenerate and/or highly plastic. Studies are ongoing to assess the consequences to the developing central auditory system of initiating electrical stimulation at later ages.

Age Factors↗

PubMed2002

Molecular epidemiology of multidrug-resistant tuberculosis, New York City, 1995-1997.

From January 1, 1995, to December 31, 1997, we reviewed records of all New York City patients who had multidrug-resistant tuberculosis (MDRTB); we performed insertion sequence (IS) 6110-based DNA genotyping on the isolates. Secondary genotyping was performed for low IS6110 copy band strains. Patients with identical DNA pattern strains were considered clustered. From 1995 through 1997, MDRTB was diagnosed in 241 patients; 217 (90%) had no prior treatment history, and 166 (68.9%) were born in the United States or Puerto Rico. Compared with non-MDRTB patients, MDRTB patients were more likely to be born in the United States, have HIV infection, and work in health care. Genotyping results were available for 234 patients; 153 (65.4%) were clustered, 126 (82.3%) of them in eight clusters of >or=4 patients. Epidemiologic links were identified for 30 (12.8%) patients; most had been exposed to patients diagnosed before the study period. These strains were likely transmitted in the early 1990 s when MDRTB outbreaks and tuberculosis transmission were widespread in New York.

Adolescent↗