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Articles by A Sharma
Total Records ( 8 ) for A Sharma
  J Jeffery , A Sharma and R. M Ayling
  Background

In vitro haemolysis is a common occurrence in clinical laboratories and causes a spurious increase in potassium. In the past, haemolysis was sought by visual inspection but is now commonly detected by automated measurement of the haemolytic index (HI). This study compared detection of haemolysis in adult and neonatal samples by inspection and measurement of HI and verified that a single equation is appropriate to correct for the increase in potassium in both haemolysed samples.

Methods

Laboratory staff inspected samples for haemolysis and their observations were compared with the measured HI. The potassium concentrations and haemolytic indices of 613 adult and 523 neonatal samples were correlated to derive equations to compensate for the increase in potassium with increase in HI. These were found not to differ significantly and a single equation for use in both populations was derived.

Results

The presence of icterus was found to decrease ability to detect haemolysis on inspection. The mean (95% confidence limits) potassium increase per unit HI was 0.0094 mmol/L (0.0078–0.0103 mmol/L) for adults and 0.0108 mmol/L (0.0094–0.0121 mmol/L) for neonates. The equation developed to compensate for potassium release in haemolysed samples was: adjusted potassium = measured potassium – (HI in µmol/L x 0.01).

Conclusion

The use of HI rather than visual inspection is particularly recommended in neonates whose serum tends to be icteric. It can be used in the same correction equation as in adults to compensate for potassium released due to haemolysis and facilitate reporting a qualitative comment to assist in immediate clinical management.

  B Lu , N Congdon , X Liu , K Choi , D. S. C Lam , M Zhang , M Zheng , Z Zhou , L Li , A Sharma and Y. Song
 

Objective  To study the associations between near work, outdoor activity, and myopia among children attending secondary school in rural China.

Methods  Among a random cluster sample of 1892 children in Xichang, China, subjects with an uncorrected acuity of 6/12 or less in either eye (n = 984) and a 25% sample of children with normal vision (n = 248) underwent measurement of refractive error. Subjects were administered a questionnaire on parental education, time spent outdoors, and weekly time spent engaged in and preferred working distance for a variety of near-work activities.

Results  Among 1232 children with refraction data, 998 (81.0%) completed the near-work survey. Their mean age was 14.6 years (SD, 0.8 years), 55.6% were girls, and 83.1% had myopia of –0.5 diopters or less (more myopia) in both eyes. Time and diopter-hours spent on near activities did not differ between children with and without myopia. In regression models, time spent on near activities and time outdoors were unassociated with myopia, adjusting for age, sex, and parental education.

Conclusions  These and other recent results raise some doubts about the association between near work and myopia. Additional efforts to identify other environmental factors associated with myopia risk and that may be amenable to intervention are warranted.

  M Zhang , N Congdon , L Li , Y Song , K Choi , Y Wang , Z Zhou , X Liu , A Sharma , W Chen and D. S. C. Lam
 

Objective  To study the effect of myopia and spectacle wear on bicycle-related injuries in rural Chinese students. Myopia is common among Chinese students but few studies have examined its effect on daily activities.

Methods  Data on visual acuity, refractive error, current spectacle wear, and history of bicycle use and accidents during the past 3 years were sought from 1891 students undergoing eye examinations in rural Guangdong province.

Results  Refractive and accident data were available for 1539 participants (81.3%), among whom the mean age was 14.6 years, 52.5% were girls, 26.8% wore glasses, and 12.9% had myopia of less than –4 diopters in both eyes. More than 90% relied on bicycles to get to school daily. A total of 2931 accidents were reported by 423 participants, with 68 requiring medical attention. Male sex (odds ratio, 1.55; P < .001) and spectacle wear (odds ratio, 1.38; P = .04) were associated with a higher risk of accident, but habitual visual acuity and myopia were unassociated with the crash risk, after adjusting for age, sex, time spent riding, and risky riding behaviors.

Conclusion  These results may be consistent with data on motor vehicle accidents implicating peripheral vision (potentially compromised by spectacle wear) more strongly than central visual acuity in mediating crash risk.

  P Paliwal , J Gupta , R Tandon , A Sharma and R. B. Vajpayee
 

Objective  To report Avellino corneal dystrophy and underlying R124H mutation in 2 families of Indian origin.

Methods  Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected individuals. Amplification of transforming growth factor β-induced gene (TGFBI) using polymerase chain reaction followed by direct sequencing was carried out to determine the mutations underlying the disorder. A detailed clinical evaluation was undertaken to establish a genotype-phenotype correlation.

Results  R124H mutation resulting from a missense heterozygous substitution of G to A at nucleotide 418 of TGFBI was detected in all affected members of the 2 families. The affected individuals were clinically diagnosed as having granular corneal dystrophy. Histopathological examination was not done because no surgical intervention was undertaken.

Conclusions  To our knowledge, this is the first report of Avellino corneal dystrophy from India clinically diagnosed as granular corneal dystrophy, emphasizing that TGFBI screening is essential for the accurate diagnosis and classification of corneal dystrophies.

Clinical Relevance  Molecular genetics is a useful tool for accurate diagnosis and classification of corneal dystrophies. All autosomal dominant stromal dystrophies should be screened for underlying mutations in TGFBI because the clinical and phenotypic appearance is variable.

  O Zabirnyk , W Liu , S Khalil , A Sharma and J. M. Phang
 

Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.

  A Sharma and M. Vijayan
 

The three crystal structures reported here provide details of the interactions of mannose and the mannosyl--1,3-mannose component of a pentamannose with banana lectin and evidence for the binding of glucosyl--1,2-glucose to the lectin. The known structures involving the lectin include a complex with glucosyl-β-1,3-glucose. Modeling studies on the three disaccharide complexes with the reducing end and the nonreducing end at the primary binding site are also provided here. The results of the X-ray and modeling studies show that the disaccharides with an -1,3 linkage prefer to have the nonreducing end at the primary binding site, whereas the reducing end is preferred at the site when the linkage is β-1,3 in mannose/glucose-specific β-prism I fold lectins. In the corresponding galactose-specific lectins, however, -1,3-linked disaccharides cannot bind the lectin with the nonreducing end at the primary binding site on account of steric clashes with an aromatic residue that occurs only when the lectin is galactose-specific. Molecular dynamics simulations based on the known structures involving banana lectin enrich the information on lectin–carbohydrate interactions obtained from crystal structures. They demonstrate that conformational selection as well as induced fit operate when carbohydrates bind to banana lectin.

  T Aye , E Toschi , A Sharma , D Sgroi and S. Bonner Weir
 

Markers of β-cell maturity would be useful in staging the differentiation of stem/progenitor cells to β-cells whether in vivo or in vitro. We previously identified markers for newly formed β-cells in regenerating rat pancreases after 90% partial pancreatectomy. To test the generality of these markers of newly formed β-cells, we examined their expression during the perinatal period, a time of recognized β-cell immaturity. We show by semiquantitative RT-PCR and immunostaining over the time course from embryonic day 18/20 to birth, 1 day, 2 days, 3 days, 7 days, and adult that MMP-2, CK-19, and SPD are truly markers of new and immature β-cells and that their expression transiently peaks in the perinatal period and is not entirely synchronous. The shared expression of these markers among fetal, newborn, and newly regenerated β-cells, but not adult, strongly supports their use as potential markers for new β-cells in the assessment of both the maturity of stem cell–derived insulin-producing cells and the presence of newly formed islets (neogenesis) in the adult pancreas. (J Histochem Cytochem 58:369–376, 2010)

  C. S Rex , L. Y Chen , A Sharma , J Liu , A. H Babayan , C. M Gall and G. Lynch
 

The releasable factor adenosine blocks the formation of long-term potentiation (LTP). These experiments used this observation to uncover the synaptic processes that stabilize the potentiation effect. Brief adenosine infusion blocked stimulation-induced actin polymerization within dendritic spines along with LTP itself in control rat hippocampal slices but not in those pretreated with the actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase (PAK). A search for the upstream origins of these effects showed that adenosine suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase (ROCK) inhibitor reproduced adenosine's effects on cofilin phosphorylation, spine actin polymerization, and LTP, whereas a Rac inhibitor did not. However, inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments.

 
 
 
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