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S Selvaraj

Publications and source records attributed to S Selvaraj.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: application of long-range order to folding rate prediction.

The contact order is believed to be an important factor for understanding protein folding mechanisms. In our earlier work, we have shown that the long-range interactions play a vital role in protein folding. In this work, we analyzed the contribution of long-range contacts to determine the folding rate of two-state proteins. We found that the residues that are close in space and are separated by at least ten to 15 residues in sequence are important determinants of folding rates, suggesting the presence of a folding nucleus at an interval of approximately 25 residues. A novel parameter "long-range order" has been proposed to predict protein folding rates. This parameter shows as good a relationship with the folding rate of two-state proteins as contact order. Further, we examined the minimum limit of residue separation to determine the long-range contacts for different structural classes. We observed an excellent correlation between long-range order and folding rate for all classes of globular proteins. We suggest that in mixed-class proteins, a larger number of residues can serve as folding nuclei compared to all-alpha and all-beta proteins. A simple statistical method has been developed to predict the folding rates of two-state proteins using the long-range order that produces an agreement with experimental results that is better or comparable to other methods in the literature.

Binding Sites↗
PubMed2001

Clusters in alpha/beta barrel proteins: implications for protein structure, function, and folding: a graph theoretical approach.

The alpha/beta barrel fold is adopted by most enzymes performing a variety of catalytic reactions, but with very low sequence similarity. In order to understand the stabilizing interactions important in maintaining the alpha/beta barrel fold, we have identified residue clusters in a dataset of 36 alpha/beta barrel proteins that have less than 10% sequence identity within themselves. A graph theoretical algorithm is used to identify backbone clusters. This approach uses the global information of the nonbonded interaction in the alpha/beta barrel fold for the clustering procedure. The nonbonded interactions are represented mathematically in the form of an adjacency matrix. On diagonalizing the adjacency matrix, clusters and cluster centers are obtained from the highest eigenvalue and its corresponding vector components. Residue clusters are identified in the strand regions forming the beta barrel and are topologically conserved in all 36 proteins studied. The residues forming the cluster in each of the alpha/beta protein are also conserved among the sequences belonging to the same family. The cluster centers are found to occur in the middle of the strands or in the C-terminal of the strands. In most cases, the residues forming the clusters are part of the active site or are located close to the active site. The folding nucleus of the alpha/beta fold is predicted based on hydrophobicity index evaluation of residues and identification of cluster centers. The predicted nucleation sites are found to occur mostly in the middle of the strands. Proteins 2001;43:103-112.

Algorithms↗
PubMed2001

Thermodynamic database for protein-nucleic acid interactions (ProNIT).

MOTIVATION: Protein-nucleic acid interactions are fundamental to the regulation of gene expression. In order to elucidate the molecular mechanism of protein-nucleic acid recognition and analyze the gene regulation network, not only structural data but also quantitative binding data are necessary. Although there are structural databases for proteins and nucleic acids, there exists no database for their experimental binding data. Thus, we have developed a Thermodynamic Database for Protein-Nucleic Acid Interactions (ProNIT). RESULTS: We have collected experimentally observed binding data from the literature. ProNIT contains several important thermodynamic data for protein-nucleic acid binding, such as dissociation constant (K(d)), association constant (K(a)), Gibbs free energy change (DeltaG), enthalpy change (DeltaH), heat capacity change (DeltaC(p)), experimental conditions, structural information of proteins, nucleic acids and the complex, and literature information. These data are integrated into a relational database system together with structural and functional information to provide flexible searching facilities by using combinations of various terms and parameters. A www interface allows users to search for data based on various conditions, with different display and sorting options, and to visualize molecular structures and their interactions. AVAILABILITY: ProNIT is freely accessible at the URL http://www.rtc.riken.go.jp/jouhou/pronit/pronit.html.

Amino Acid Sequence↗
PubMed2001

Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis.

PURPOSE: To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive bacterial keratitis. METHODS: Patients with a microbiologic diagnosis of bacterial keratitis were included in this double-masked, parallel-group study and were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3% ophthalmic solution. One drop of the study medication was instilled during the daytime according to the following schedule: every half-hour on study day 1, every hour on days 2 through 4, and every 2 hours on days 5 through 21. Healing, the primary outcome measure, was defined as complete reepithelialization, accompanied by nonprogression of stromal infiltrate for 2 days. Secondary outcome measures included signs and symptoms of infection. Patients were monitored throughout the study period for any adverse events. RESULTS: A total of 217 patients completed the study: 112 were treated with ofloxacin and 105 were treated with ciprofloxacin. Streptococcus pneumoniae was the most commonly encountered pathogen in all patients. Complete corneal reepithelialization occurred in 85% of those treated with ofloxacin and in 77% of those treated with ciprofloxacin (p = 0.32). The average time to corneal ulcer healing was 13.7 days in those treated with ofloxacin and 14.4 days in those treated with ciprofloxacin. Both treatments were well tolerated with no patient discontinuing the study because of side effects. CONCLUSION: Ofloxacin 0.3% and ciprofloxacin 0.3% ophthalmic solutions are effective and safe in the treatment of patients with culture-positive bacterial keratitis.

Adult↗
PubMed2000

The madurai intraocular lens study IV: posterior capsule opacification.

PURPOSE: To estimate the cumulative incidence of posterior capsule opacification 4 years after surgery in patients who participated in the Madurai Intraocular Lens Study and had extracapsular cataract extraction with posterior chamber intraocular lens implantation. METHODS: In the Madurai Intraocular Lens Study, 1,700 patients with best-corrected visual acuity 20/120 or worse in the better eye had extracapsular cataract extraction with posterior chamber intraocular lens implantation, and 1,474 (86.7%) of these completed the 1-year follow-up examination. From this group of 1,474 pseudophakic patients, 400 were randomly selected for reexamination 4 years after the original surgery. The eye that was operated on was examined by an ophthalmologist who was involved in the 1-year follow-up examinations and posterior capsule opacification grading. A grading of I to III was used to reflect the degree of opacification. With grades II and III, posterior capsule opacification detectable with an undilated pupil was present in the central axis. RESULTS: Three hundred twenty-seven (81.8%) of the selected population were examined between October 1997 and December 1998. Thirty-four (8.5%) were confirmed as being deceased, and 39 (9.8%) were unavailable for follow-up. The median age was 60 years, and 57.2% were women. The 4-year incidence of grade II or III posterior capsule opacification, including eyes already treated with laser capsulotomy, was 13.1% (95% confidence interval [CI], 9.7% to 17.3%). Each year of increased age was associated with a decreased risk of posterior capsule opacification (odds ratio, 0.96; 95% CI, 0.92 to 1.00). Based on best-corrected visual acuity of 20/40 or worse without co-existing pathology, the 4-year incidence of posterior capsule opacification was 13.5%. CONCLUSION: Because patients with relatively mature cataracts routinely receive extracapsular cataract extraction with posterior chamber intraocular lens implantation instead of the traditional intracapsular extraction, the subsequent need for laser capsulotomy may be less than that anticipated, based on previous reports.

Adult↗
PubMed2000

Differential modulation of xenobiotic metabolizing enzymes by vanadium during diethylnitrosamine-induced hepatocarcinogenesis in Sprague-Dawley rats.

Effect of vanadium on hepatic xenobiotic biotransformation in rats exposed to diethylnitrosamine (DENA, 200 mg/kg body weight, intraperitoneally) was investigated to elucidate a possible mechanism of vanadium mediated prevention of chemical carcinogenesis. Vanadium supplementation (0.5 ppm ad libitum with drinking water), at different phases before and after DENA treatment, significantly modulated the decrease in contents of total cytochrome P-450, cytochrome b5, activity of nicotinamide adenine dinucleotide phosphate (NADPH), (reduced form) cytochrome reductase, and uridine diphospho-glucuronyl transferase (UDPGT) in microsomal fractions of whole liver, hyperplastic nodules (HNs) and non nodular surrounding parenchyma (NNSP) as induced by DENA, 20 weeks following its administration. Supplementary vanadium had also substantial influence on the activities of cytosolic enzymes, like, uridine diphospho (UDP)-glucose dehydrogenase and NAD(P)H: quinone oxidoreductase (DT-diaphorase) in the concerned tissue which were observed to be remarkably decreased as a result of DENA treatment in comparison to that of the control counterparts. However, vanadium was found to have little or no effect on the lowering ofaryl hydrocarbon hydroxylase (AHH) activity by DENA administration. On the basis of significant modulation of DENA induced alterations in cytosolic and microsomal enzyme activity it can be presumed that the chemoprotective effect of vanadium might be mediated through elevation of phase II conjugating enzymes which in turn, lead to a move and shift of metabolic profile that reduces the intracellular concentration of carcinogen derived reactive intermediates.

Animals↗
PubMed1999

Importance of long-range interactions in protein folding.

Long-range interactions play an active role in the stability of protein molecules. In this work, we have analyzed the importance of long-range interactions in different structural classes of globular proteins in terms of residue distances. We found that 85% of residues are involved in long-range contacts. The residues occurring in the range of 4-10 residues apart contribute more towards long-range contacts in all-alpha proteins while the range is 11-20 in all-beta proteins. The hydrophobic residues Cys, Ile and Val prefer the 11-20 range and all other residues prefer the 4-10 range. The residues in all-beta proteins have an average of 3-8 long-range contacts whereas the residues in other classes have 1-4 long-range contracts. Furthermore, the preference of residue pairs to the folding and stability will be discussed.

Amino Acids↗
PubMed1999

Studies on the genotoxicity of endosulfan in bacterial systems.

Endosulfan, an organochlorine pesticide, was subjected to the differential sensitivity assay in repair-deficient and repair-proficient strains of Escherichia coli K12, prophage lambda induction assay in WP2s (lambda) and mutation induction in E. coli K12. The induction of umu gene expression with endosulfan was studied also in Salmonella typhimurium TA1535/pSK1002 cells. The differential sensitivity assay revealed that the recA 13 strain was the most sensitive. Endosulfan induced prophage lambda in E. coli and umu gene expression in S. typhimurium cells; however, the extent of the effects were low. Endosulfan also induced a dose-dependent increase in forward mutations in E. coli K12 cells from ampicillin sensitivity to ampicillin resistance. Our studies indicate the genotoxic potential of endosulfan and the role of the recA gene in the repair of endosulfan-induced DNA damage.

Ampicillin↗
PubMed1999

Influence of medium and long range interactions in protein folding.

Protein structures are stabilized by both local and long range interactions. In this work, we analyze the residue-residue contacts and the role of medium- and long-range interactions in globular proteins belonging to different structural classes. The results show that while medium range interactions predominate in all-alpha class proteins, long-range interactions predominate in all-beta class. Based on this, we analyze the performance of several structure prediction methods in different structural classes of globular proteins and found that all the methods predict the secondary structures of all-alpha proteins more accurately than other classes. Also, we observed that the residues occurring in the range of 21-30 residues apart contributes more towards long-range contacts and about 85% of residues are involved in long-range contacts. Further, the preference of residue pairs to the folding and stability of globular proteins is discussed.

Amino Acids↗
PubMed1998

Importance of long-range interactions in (alpha/beta)8 barrel fold.

Protein structures are stabilized by both local and long-range interactions. In this work, we analyzed the importance of long-range interactions in (alpha/beta)8 barrel proteins in terms of residue distances. We found that the residues occurring in the range of 21-30 residues apart contribute more toward long-range contacts. Indeed, about 50% of successive strands in these proteins are found to occur at a sequential distance of 21-30 residues. The aromatic amino acid residues Phe, Trp, and Tyr prefer the 4-10 range and all other residues prefer the 21-30 range. Hydrophobic-hydrophobic residue pairs are the most preferred ones for long-range interactions and they may play a key role in the folding and stabilization of (alpha/beta)8 barrel proteins.

Amino Acids↗
PubMed1998

The Madurai Intraocular Lens Study. III: Visual functioning and quality of life outcomes.

PURPOSE: To compare the effects of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) vs intracapsular cataract extraction with aphakic glasses (ICCE-AG) on everyday visual functioning and quality of life. METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilateral vision-impaired patients, aged 40 to 75 years, with operable cataract were randomly assigned to receive one of the two treatment options. One half in each group were randomly selected for interviewer administration of visual functioning and quality of life questionnaires before surgery and at 6 and 12 months after surgery. RESULTS: Both ICCE-AG and ECCE/PC-IOL produced dramatic improvements in visual functioning and quality of life scores. Patients receiving ECCE/PC-IOL reported larger beneficial changes than did those receiving ICCE-AG, compatible with additional beneficial effects of a moderate magnitude for visual functioning and of a smaller beneficial magnitude for quality of life. All between-group differences were highly statistically significant (P < .00001). The additional benefits of ECCE/PC-IOL are not explained by visual acuity differences. A higher proportion of patients in the ICCE-AG group reported problems on a vision problem checklist at 6 months (more than 50%) than did patients in the ECCE/PC-IOL group (approximately 30%). CONCLUSIONS: In this developing-country setting, ICCE-AG and ECCE/PC-IOL were associated with substantial benefits in improved everyday vision function and vision-related quality of life. Patients who received ECCE/PC-IOL reported greater benefits and fewer problems with vision than did patients who received ICCE-AG.

Adult↗
PubMed1998

An analysis of the amino acid clustering pattern in (alpha/beta)8 barrel proteins.

The (alpha/beta)8 barrel proteins, in spite of having a common fold, do not show any sequence similarity. In order to understand the factors which are responsible for maintaining the common fold, the three-dimensional structures of 36 (alpha/beta)8 barrel proteins are analyzed for the presence of identical amino acid clusters or physicochemically similar clusters. The results reveal 14 identical amino acid clusters and a large number of physicochemically similar clusters. Further analysis of the similar clusters points to the conservation of secondary structures, the presence of pairs of residues occupying topologically equivalent secondary structures, and the presence of certain key residues which may play a vital role in directing and stabilizing the (alpha/beta)8 barrel fold.

Amino Acids↗
PubMed1998

Protein secondary structure prediction in different structural classes.

Information about the secondary structure of a protein can be helpful in understanding its native folded state. In previous work, it was shown that the medium-range interactions predominate in all-alpha class and the long-range interactions predominate in all-beta class proteins. Based on this, in this work the performance of several structure prediction methods in different structural classes of globular proteins was analyzed. It was found that all the methods predict the secondary structures of all-alpha proteins more accurately than other classes.

Protein Structure, Secondary↗
PubMed1998

Visual functioning and quality of life outcomes among cataract operated and unoperated blind populations in Nepal.

BACKGROUND: Visual acuity and vision related quality of life outcomes in cataract surgery were evaluated in a population based survey in two geographic zones in Nepal. METHODS: Case finding was based on random sampling using a stratified cluster design with door to door enumeration of people aged > or = 45 years followed by eye examinations at village sites. All aphakics/pseudophakics, those with visual acuity less than 6/60 in either eye, and a sample of those with normal visual acuity were administered visual functioning (VF) and quality of life (QOL) questionnaires. RESULTS: 15% of the 159 cataract operated cases had presenting visual acuity > or = 6/18 in both eyes, 38% with best corrected visual acuity. 21% were still blind with presenting visual acuity < 6/60 in both eyes, 7% with best correction. On a 0-100 scale, mean VF and QOL scores were 87.2 and 93.9 respectively in normally sighted unoperated individuals, dropping to 15.6 and 29.5 for those severely blind (< 3/60). Among the cataract operated, mean VF and QOL scores were 47.5 and 55.4, respectively. VF and QOL scores correlated with vision status at statistically significant levels (p < 0.0001). CONCLUSION: Cataract surgery outcomes, whether measured by traditional visual acuity or by patient reported VF/QOL, are at levels many would consider unacceptably low. It is apparent that in the quest to reduce cataract blindness much more attention must be given to improving surgery outcomes.

Aged↗
PubMed1997

Measurements of vision function and quality of life in patients with cataracts in southern India. Report of instrument development.

OBJECTIVE: To develop and validate vision function (VF) and quality of life (QOL) instruments in patients with cataracts in the context of large volume surgery in a developing country. MATERIALS AND METHODS: The instruments were developed using a consensus approach. One hundred patients who were undergoing cataract surgery at Aravind Eye Hospital, Madurai, India, were interviewed preoperatively and 3 and 12 months postoperatively. Standard clinical procedures were followed, including measurement of visual acuity. Between-interviewer reproducibility was measured by repeated administration of the preoperative questionnaire. Within-interviewer reproducibility was measured preoperatively in a separate study of 50 patients. RESULTS: Preoperative scores from the VF and QOL instruments were significantly associated with visual acuity (r = 0.4). Internal reliability (Cronbach alpha) was greater than .9. Both instruments showed large changes after surgery, with effect sizes of 3 or greater for most VF scales (range, 1.8-3.7) and 1 or greater for QOL scales (range, 1.0-2.2). Changes in visual acuity after surgery were correlated with changes in the VF (r = 0.44) and QOL (r = 0.41) scale scores. Between-interviewer reproducibility was acceptable (total VF scale, Spearman r = 0.7; total QOL scale; r = 0.74). The kappa values were lower for within-interviewer reproducibility. CONCLUSIONS: The study provided strong evidence for the validity, reproducibility, and responsiveness of the instruments, and for the feasibility of using them in the setting of a large volume of cataract surgery in a developing country.

Cataract↗
PubMed1997

A long-term dose-response study of mitomycin in glaucoma filtration surgery.

OBJECTIVE: To establish the long-term, dose-response relationship between the concentration of and duration of exposure to mitomycin to a decrease in intraocular pressure (IOP) and fewer complications. METHODS: We performed a prospective double-masked, placebo-controlled, 1-year study evaluating the decrease in IOP and fewer complications of fornix-based trabeculectomy surgery in 300 eyes equally divided among therapy with placebo; mitomycin, 0.2 mg/ mL, applied for 2 minutes; mitomycin, 0.4 mg/mL, applied for 4 minutes; or mitomycin, 0.4 mg/mL, applied for 2 minutes. All of the eyes had vertical and horizontal cup-disc ratios greater than 0.7. RESULTS: We observed significant treatment-related differences in IOP, with a decrease in IOP in all 3 mitomycin-treated groups for all of the times beyond 1 month. The number of eyes achieving strict IOP control and the development of cataract suggest a possible dose-response effect for concentration and time of exposure. Progressive lens opacification was the most frequent complication in 54 eyes (18.1%). The incidence of progressive lens changes markedly increased in subjects receiving 4 minutes of mitomycin therapy. Cataract formation was unrelated to IOP. Other complications were rare. Macular folds developed in 6 patients, with visual acuity returning to better than 20/40 in all but 1 patient. CONCLUSIONS: A possible dose-response relationship seemed to exist between the concentration of and duration of exposure to mitomycin. Length of exposure seems to be more important than concentration. The benefits of additional decreases in IOP must be weighed against the potential for increases in the risk of complications.

Antibiotics, Antineoplastic↗
PubMed1997

Uveitis associated with an epidemic outbreak of leptospirosis.

PURPOSE: To define uveitis associated with leptospirosis in a clinical setting. METHODS: We present the clinical features of 73 consecutive cases of uveitis linked clinically to an outbreak of systemic leptospirosis in patients with antibodies to Leptospira species who were examined from January to September 1994. RESULTS: In 73 patients, the pattern of ocular involvement was unilateral in 35 and bilateral in 38. Panuveitis was seen in 106 eyes (95.5%), retinal periphlebitis in 57 eyes (51.4%), and hypopyon in 14 eyes (12.6%). Anterior uveitis alone without hypopyon was observed in three eyes (2.7%), whereas vitreous inflammatory reaction alone was seen in two eyes (1.8%). Sixty of 73 patients (82.2%) or 91 of 111 eyes (82.0%) were followed up for 8 months. Final visual acuity was 6/6 (20/20) in 47 eyes (52%) and improved during treatment, although not up to 6/6, in 15 eyes (16%). Twenty-eight eyes (31%) maintained same vision, and one eye showed deterioration of vision. CONCLUSION: Uveitis associated with leptospirosis may manifest as unilateral or bilateral uveitis, anterior uveitis, or panuveitis. The prognosis is generally good in this entity, even when the inflammation is severe. Awareness of this disease in endemic areas is important in order to differentiate it from other uveitic entities, especially in young male patients in whom other immunologic uveitides are also common.

Adult↗