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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 55 records · Page 3Linked to original sources

fMRI Measures of perceptual filling-in in the human visual cortex.

Filling-in refers to the tendency of stabilized retinal stimuli to fade and become replaced by their background. This phenomenon is a good example of central brain mechanisms that can selectively add or delete information to/from the retinal input. Importantly, such cortical mechanisms may overlap with those that are used more generally in visual perception. In order to identify cortical areas that contribute to perceptual filling-in, we used functional magnetic resonance imaging to image activity in the visual cortex while subjects experienced filling-in. Nine subjects viewed an achromatic disc with slightly higher luminance than the background and indicated the presence or absence of filling-in by a keypress. The disc was placed in either the upper or lower left quadrant. Similar high-contrast stimuli were used to map out the retinotopic representation of the disc. Unexpectedly, the lower-field high-contrast stimulus produced more parietal cortex activation than the upper-field condition, indicating preferential representation of the lower field by attentional control mechanisms. During perceptual filling-in, we observed significant contralateral reductions in activation in lower-tier retinotopic areas V1 and V2. In contrast, increased activation was consistently observed in visual areas V3A and V4v, higher-level cortex in the intraparietal sulcus, posterior superior temporal sulcus, and the ventral occipital-temporal region, as well as the pulvinar. The filling-in activation pattern was remarkably similar for both the upper- and lower-field conditions. Behaviorally, filling-in was reported to be easier for the lower visual field, and filling-in periods were longer for the lower than the upper quadrant. We suggest this behavioral asymmetry may be partially due to the preferential parietal representation of the lower field. The results lead us to propose that perceptual filling-in recruits high-level control mechanisms to reconcile competing percepts, and alters the normal image-related signals at the first stages of cortical processing. Moreover, the overall pattern of activation during filling-in resembles that seen in other studies of perceptually bistable stimuli, including binocular rivalry, indicating common control mechanisms.

Adult↗

Cricothyroidotomy: a short-term measure for elective ventilation in a patient with challenging neck anatomy.

Cricothyroidotomy is a well established technique of airway management in emergency situations where translaryngeal intubation cannot be achieved. This case report describes a case where cricothyroidotomy was used for elective ventilation for short period of 48 hours in a patient who had a vocal cord palsy, supraglottic oedema and inflammation. Surgical tracheostomy was considered the preferred option, but this was deemed impossible due to the challenging neck anatomy in this case.

Aged↗

Registry of shoulder arthroplasty - the Scottish experience.

INTRODUCTION: Recognising that timely dissemination of information in the orthopaedic community was important and in the absence of any national guidelines for shoulder arthroplasty, the Scottish shoulder arthroplasty registry, a voluntary registry, was started in 1996. The goals of the registry were to assess contemporary practice, provide a benchmark against which surgeons could compare their practice, identify risk factors for a poor outcome, and to improve outcomes through continuous feedback to the participating surgeons. PATIENTS AND METHODS: A standardised proforma was used to collect information on the diagnostic and demographic data, type of procedure performed, type of implant used, any associated procedures performed in conjunction with the arthroplasty, and peri-operative complications. Postoperative pain, activity and patient satisfaction were assessed annually using another standardised proforma. RESULTS: Twenty surgeons have contributed to the register and 451 shoulder arthroplasties were registered over a 5-year period. Of patients, 23.2% were male and 76.8% female. The mean age was 65 years (range, 37-90 years). Shoulder arthroplasty was commonly performed for rheumatoid arthritis followed by trauma, osteoarthritis and avascular necrosis of the humeral head. Overall, 397 (88%) patients had a hemi-arthroplasty and 54 (12%) had a total shoulder replacement. Of the 54 cases that had a glenoid replacement, 28 were performed for inflammatory arthritis, 21 for osteoarthritis and 5 were for revisions. The humeral component was cemented in 204 (45%) cases, 160 of whom had a shoulder replacement for trauma. The glenoid component was cemented in 48 (89%) cases. Cross referencing our data with the figures of the actual number of shoulder arthroplasties performed, however, indicated that our registry at best collected only 53% of all the shoulder arthroplasties performed in Scotland annually. CONCLUSIONS: The value of a joint registry is dependent on the accuracy and completeness of the data entered. Our registry, therefore, fails as an implant registry. We believe that compliance for data registration can only be ensured if dedicated data collection staff are employed to co-ordinate the data collection and collation process.

Adult↗

Setting up chronic disease programs: perspectives from Aboriginal Australia.

OBJECTIVE: To share some perspectives on setting up programs to improve management of hypertension, renal disease, and diabetes in high-risk populations, derived from experience in remote Australian Aboriginal settings. PRINCIPLES: Regular integrated checks for chronic disease and their risk factors and appropriate treatment are essential elements of regular adult health care. Programs should be run by local health workers, following algorithms for testing and treatment, with back up from nurses. Constant evaluation is essential. COMPONENTS: Theses include testing, treatment, education for individuals and communities, skills and career development for staff, ongoing evaluation, program modification, and advocacy. Target groups, elements, and frequency of testing, as well as the reagents and treatment modalities must be designed for local circumstances, which include disease burden and impact, competing priorities, and available resources. Pilot surveys or record reviews can define target groups and conditions. Opportunistic testing will suffice if people are seen with some regularity for other conditions; otherwise, systematic screening is needed, preferably embedded in primary care streams. The chief goal of treatment is to lower blood pressure, and if the patient is diabetic, to control hyperglycemia. Many people will need multiple drugs for many years. CHALLENGES: Challenges include lack of resources, competing demands of acute care, the burden of treatment when disease rates are high, problems with information systems, and in our setting, health worker absenteeism. FUNDING: Businesses, altruistic organizations, and pharmaceutical and biotechnology companies might fund feasibility studies. Where governments or insurance companies already support health services, they must ultimately commit to chronic disease services over the long- term. Effective advocacy requires the presentation of an integrated view of chronic disease and a single cross-disciplinary program for its containment. Arguments based on preserving the economic base of societies by preventing or delaying premature death will carry most weight, as will the costs of dialysis avoided in countries that already support open-access programs.

Adult↗

A DNA vaccine that encodes rabies virus glycoprotein lacking transmembrane domain enhances antibody response but not protection.

Rabies virus (RV) glycoprotein (gp) consists of three domains: cytoplasmic, transmembrane and ectodomain. It occurs in a complete, membrane-bound form within the infected cell, but it is released from them in a deleted, secreted form lacking the transmembrane domain. This study was performed to test the importance of the transmembrane domain for the capability of the RV gp gene, introduced into mice via a recombinant plasmid (DNA vaccine), to induce immune response and protection against challenge. Although the antibody response to the secreted form of gp was higher than that to complete gp, the protective efficacy of the respective DNA vaccine against challenge was not better than that of the DNA vaccine inducing complete gp. This indicates that the transmembrane domain of RV gp is important for generating protection against rabies and should be present in RV DNA vaccines.

Animals↗

Permeation enhancers in the transmucosal delivery of macromolecules.

The present article presents a compilation of information regarding various chemical permeation enhancers useful for transmucosal delivery of macromolecules. In the recent past, biotechnology has provided a great number of macromolecules for treatment of various disorders. With the rise in importance of macromolecules, especially proteins and peptides, an enormous volume of research on various novel routes of drug delivery has been carried out. Inspite of its giving the highest and fastest bioavailability, the parenteral route is not a preferred option, due to its inconvenience and the noncompliance of patients. Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Transmucosal drug delivery with various bioavailability enhancers is receiving increasing attention as a possible alternative to parenteral delivery of macromolecules. Among the various bioavailability enhancers, chemical permeation enhancers have been most studied. Permeation enhancers reversibly modulate the permeability of the barrier layer in favor of drug absorption. Newer permeation enhancers like zonula occludin toxin, poly-L-arginine, chitosan derivatives etc have shown a significant increase in drug absorption through transmucosal routes without serious damage to the barrier layer. In particular delivery of macromolecules via the nasal and pulmonary routesusing newer permeation enhancers has emerged as a possible alternative to the parenteral delivery ofmacromolecules.

Animals↗

Detailed biochemical characterization of human placental cystatin (HPC).

A low molecular weight thiol protease inhibitor (12,500) purified from human placenta has been characterized in detail. Human placental cystatin (HPC) was found to be stable in the pH range 3.0-9.0 and temperature stability was between 40 and 100 degrees C. It does not have any disulphide groups and carbohydrate content. There was no cross-reaction between anti-HPC serum and other purified cystatins like HMW kininogens isolated from sheep plasma and phytocystatins isolated from Phaseolus mungo. The kinetics of inhibition of HPC was studied with ficin and bromelain and the comparison was made with our already reported results with papain. The respective K(i) values obtained for ficin and bromelain are 8.4 x 10(-8) M and 9.5 x 10(-8) M, respectively, whereas the value for papain was 5.5 x 10(-8) M. The values of association constants (K(ass)) for ficin and bromelain were 2.9 x 10(3) and 8.6 x 10(2) M(-1) s(-1), respectively, however, the value for papain was 3.4 x 10(4) M(-1) s(-1), the respective dissociation constant values for ficin and bromelain were 2.6 x 10(-5) and 2.1 x 10(-5) s(-1), respectively, and the value obtained for papain was 2.3 x 10(-5) s(-1). These kinetic parameters taken together along with t(1/2) values and IC(50) values imply that HPC binds more effectively to papain, then ficin and least with bromelain. Far-UV-CD analysis shows that HPC has 21.08% alpha-helical structure and significant amount of beta structure. Near-UV-CD spectra of HPC show positive peak at 280 nm indicating significant amount of tertiary interactions. The partial amino acid sequence analysis shows that HPC has highest sequence homology with chicken cystatin and Gly residue is present at position 11 rather than at conserved position 9, which has also been reported for human stefin A structure. The hydropathy plot of 1-30 amino acid residues shows that most amino acids of this stretch are present in the hydrophobic core of the protein. Owing to low molecular weight, absence of disulphide bonds and carbohydrate content HPC can be placed in type I cystatin family with some resemblance to chicken cystatin as shown by CD studies and amino acid sequence analysis.

Amino Acid Sequence↗

Distribution and fate of persistent organochlorine pesticides in coastal marine environment of Mumbai.

Multi-compartment monitoring of residue levels of OCPs in coastal marine environment of Mumbai has been studied. The concentration of total HCHs in seawater varied from 0.16 to 15.92 ng/L and concentrations of total DDT varied from 3.01 to 33.21 ng/L. The total HCH concentration in the sediment samples was in the range of 3.8 to 16.2 ng/g. Gamma-HCH contributed almost 55% to the total HCH. In sediment samples the DDT has higher mean concentration in comparison to its metabolite DDE and DDD. The concentration of total HCHs in different marine species varied from 0.87 to 33.73 ng/g and concentrations of total DDT varied from 0.38 to 34.1 ng/g. The variation in the beta-HCH in different compartments is not significant and this could be due to the high persistence and metabolically inactive nature of this isomer. The alpha-HCH is found to be more dominant in fish samples whereas the gamma-HCH is major contributor in the sediment samples.

Animals↗

All-electron exact exchange treatment of semiconductors: effect of core-valence interaction on band-gap and d-band position.

We present the first all-electron full-potential exact exchange (EXX) Kohn-Sham density functional calculations on a range of semiconductors and insulators (Ge, GaAs, CdS, Si, ZnS, C, BN, Ne, Ar, Kr, and Xe). We remove one of the main computational obstacles of such calculations by the use of a highly efficient basis for inversion of the response function. We find that the band gaps are not as close to experiment as those obtained from previous pseudopotential EXX calculations. The locations of d bands, determined using the full-potential EXX method, are in excellent agreement with experiment, irrespective of whether these are core, semicore, or valence states. We conclude that the inclusion of the core-valence interaction is necessary for accurate determination of EXX Kohn-Sham band structures and that EXX alone is not a complete answer to the band-gap problem in semiconductors.

Journal Article↗

Characterization of bacterial community structure in rhizosphere soil of grain legumes.

Molecular techniques were used to characterize bacterial community structure, diversity (16S rDNA), and activity (16S rRNA) in rhizospheres of three grain legumes: faba beans (Vicia faba L., cv. Scirocco), peas (Pisum sativum L., cv. Duel) and white lupin (Lupinus albus L., cv. Amiga). All plants were grown in the same soil under controlled conditions in a greenhouse and sampled after fruiting. Amplified 16S rDNA and rRNA products (using universal bacterial primers) were resolved by denaturing gradient gel electrophoresis (DGGE). Distinct profiles were observed for the three legumes with most of the bands derived from RNA being a subset of those derived from DNA. Comparing the total bacterial profiles with actinomycete-specific ones (using actinomycete-specific primers) highlighted the dominance of this group in the three rhizospheres. 16S PCR and RT-PCR products were cloned to construct libraries and 100 clones from each library were sequenced. Actinomycetes and proteobacteria dominated the clone libraries with differences in the groups of proteobacteria. Absence of beta-subdivision members in pea and gamma-subdivision members of proteobacteria in faba bean rhizosphere was observed. Plant-dependent rhizosphere effects were evident from significant differences in the bacterial community structure of the legume rhizospheres under study. The study gives a detailed picture of both residing and "active" bacterial community in the three rhizospheres. The high abundance of actinomycetes in the rhizospheres of mature legumes indicates their possible role in soil enrichment after the legumes are plowed into the soil as biofertilizers.

DNA, Bacterial↗

Carotid intima-medial thickness as a marker of disease activity in Takayasu's arteritis.

BACKGROUND: Assessment of disease activity in patients with Takayasu's arteritis (TA) is difficult due to absence of definitive tests. Presence of carotid intima-medial thickening has been suggested as a possible marker of inflammation and disease activity. METHODS: We evaluated common carotid artery carotid intima-medial thickness (CCA-IMT) in 56 common carotid arteries (CCAs) in 28 healthy controls and 74 CCAs in 37 patients of TA. We correlated these findings with the presence of activity as assessed by the National Institutes of Health (NIH) criteria. RESULTS: CCA-IMT was increased (>0.8 mm) in 59% of the patients with TA. In patients with disease activity, the CCA-IMT was more than in those without activity (1.5+/-0.16 vs. 0.9+/-0.2 mm, P<0.005). This is presumably because of ongoing inflammation causing abnormal thickening. Even among patients without active disease, CCA-IMT was more than in controls (0.9+/-0.2 vs. 0.6+/-0.1 mm, P<0.05) possibly due to a milder degree of inflammation or healing with fibrosis. All patients with angiographic carotid obstruction had increased CCA-IMT irrespective of whether they were active or not. However, in patients with angiographically normal carotid arteries, CCA-IMT was increased only among the patients who were active (1.4+/-0.2 vs. 0.7+/-0.04, P<0.05). Abnormal CCA-IMT as marker of disease activity had a sensitivity of 82% and specificity of 60%. On excluding patients with increased CCA-IMT who had angiographic carotid stenosis (because the increase in CCA-IMT cannot be attributed entirely to activity alone in these patients), the specificity increased to 70%. CONCLUSION: Increased CCA-IMT is a reliable marker of active disease, especially in the absence of angiographically visible carotid disease.

Adolescent↗

Crystal structure of a calcium-induced dimer of two isoforms of cobra phospholipase A2 at 1.6 A resolution.

The calcium-induced formation of a complex between two isoforms of cobra venom phospholipase A2 reveals a novel interplay between the monomer-dimer and activity-inactivity transitions. The monodispersed isoforms lack activity in the absence of calcium ions while both molecules gain activity in the presence of calcium ions. At concentrations higher than 10 mg/ml, in the presence of calcium ions, they dimerize and lose activity again. The present study reports the crystal structure of a calcium-induced dimer between two isoforms of cobra phospholipase A2. In the complex, one molecule contains a calcium ion in the calcium binding loop while the second molecule does not possess an intramolecular calcium ion. However, there are two calcium ions per dimer in the structure. The second calcium ion is present at an intermolecular site and that is presumably responsible for the dimerization. The calcium binding loops of the two molecules adopt strikingly different conformations. The so-called calcium binding loop in the calcium-containing molecule adopts a normal conformation as generally observed in other calcium containing phospholipase A(2) enzymes while the conformation of the corresponding loop in the calcium free monomer deviates considerably with the formation of a unique intraloop Gly33 (N)-Cys27 (O) = 2.74 A backbone hydrogen bond. The interactions of Arg31 (B) with Asp49 (A) and absence of calcium ion are responsible for the loss of catalytic activity in molecule A while interactions of Arg2 (B) with Tyr52 (B) inactivate molecule B.

Animals↗

Attainment of peak bone mass and bone turnover rate in relation to estrous cycle, pregnancy and lactation in colony-bred Sprague-Dawley rats: suitability for studies on pathophysiology of bone and therapeutic measures for its management.

Alteration in biochemical markers of bone turnover and bone mineral density (BMD) of whole body and isolated femur and tibia in relation to age, estrous cycle, pregnancy and lactation and suitability of use of rat as model for studies on pathophysiology of bone and therapeutic measures for its management were investigated. Immature rats (1, 1.5 and 2 month of age; weighing, respectively, 39.3+/-1.0, 67.8+/-2.4 and 87.2+/-5.2 g) exhibited high rate of bone turnover, as evidenced by high serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. However, their BMD (whole body or of isolated long bones) was below measurable levels. Marked increase in body weight at 3 months (185.5+/-5.2 g) was associated with low serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. Biochemical markers and BMD attained at puberty at 3 months were maintained until 36 month of age. No significant change in serum calcium was observed with increasing age or on any of the biomarkers during estrous cycle, and BMD of femur and tibia isolated during proestrus and diestrus stages was almost similar. Onset of pregnancy was associated with significant increase in serum total alkaline phosphatase and osteocalcin levels, but serum calcium, urine calcium/creatinine ratio or BMD of whole body or isolated long bones were not significantly different from that at proestrus stage. No marked change, except increase in body weight (P<0.05), was also evident in these parameters between days 5 and 19 of pregnancy, irrespective of number of implantations in the uterus. A significant decrease in BMD of isolated femur (neck and mid-shaft regions) was observed on days 5 and 21 of lactation as compared to that during pregnancy or diestrus/proestrus stages of estrous cycle; the decrease being almost similar in females lactating two or six young ones. BMD of isolated tibia (global and region proximal to tibio-fibular separation point), though generally lower than that during cycle and pregnancy, was statistically non-significant. However, clear evidence of occurrence of osteoporosis during lactation, with decrease in BMD of >2.5 x S.D. in isolated femur (global, neck and mid-shaft) as well as tibia (global) was observed only when BMD data was analysed on T-/Z-score basis. Serum biochemical markers of bone turnover, too, were significantly increased in comparison to cyclic rats. Findings demonstrate marked increase in body weight and bone turnover during first 3 months of age, direct correlation between peak bone mass and onset of puberty at 3 months of age and increase in bone resorption rate during lactation. Finding of the study while might suggests possible use of rat as useful model for studies on bone turnover rate during lactation and post-weaning periods and extrapolation of the result to the human situation, but not in relation to ageing.

Age Factors↗