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Biomedical subjects

K Ramnarayan

Publications and source records attributed to K Ramnarayan.

At least 19 recordsLinked to original sources
PubMed2005

Anatomy that must be taught to a medical undergraduate: an interview-based survey in an Indian medical school.

Confusion still exists about the anatomy to be taught to the medical undergraduate. We did an interview-based survey at the Melaka Manipal Medical College in Manipal, India, to try to evaluate the quantum of anatomy that should be taught to the medical undergraduate. The results suggest that excluding trivia and making anatomy more clinically oriented would be advantageous. A hybrid approach to anatomy including both problem-based learning and discipline-based curricula would be a better option than the regional or systemic approaches.

Anatomy↗
PubMed2005

Self-directed learning.

Explore the source record for details and available documents.

Education, Medical, Undergraduate↗
PubMed2005

Student perspectives of assessment by TEMM model in physiology.

Assessment is the process by which the teacher and the student gain knowledge about student progress. Assessment systems should aim at evaluating the desired learning outcomes. In Melaka Manipal Medical College, (Manipal Campus), Manipal, India, the TEMM model (consisting of 4 assessment methods: Triple Jump Test, essay incorporating critical thinking questions, Multistation Integrated Practical Examination, and multiple choice questions) was introduced to 30 refresher students in the fourth block of the academic year. At the end of the block, a questionnaire was distributed to ask the students to rank the different assessments in the order of their preference with respect to seven items. Analysis of the results showed that not a single type of assessment was ranked highest for all the seven items, proving the earlier observation that a single assessment does not fulfill all aspects of assessment and that there is a need for an evaluating system with multiple ways of assessment.

Education, Medical, Undergraduate↗
PubMed2004

Clinically oriented physiology teaching: strategy for developing critical-thinking skills in undergraduate medical students.

Medicine is an applied science, interpreting evidence and applying it to real life by using clinical reasoning skills and experience. COPT (clinically oriented physiology teaching) was incorporated in physiology instruction aiming to relate the study of physiology to real-life problems, to generate enthusiasm and motivation for learning, and to demonstrate the vocational relevance of physiology among students by integrating clinical experience with teaching. COPT consisted of two elements: 1) critical-thinking questions (CTQ) and 2) clinical case studies. After a few topics were taught, CTQ and case studies were given as an assignment. Answers were discussed in the next class. Two exams, each of which contained CTQ and recall questions, were conducted, one before (exam 1) and one after (exam 2) the implementation of COPT. Analysis of student performance in the examinations revealed that the students did better in exam 2 (P < 0.0001). Feedback from students indicated that this method was useful and challenging.

Education, Medical, Undergraduate↗
PubMed2002

Learning approaches and learning difficulties: a comparison of Indian and Nepali dental science students.

This study explored the difference in learning approaches and difficulties of Nepali and Indian undergraduate students of dental science. A locally developed inventory was used to measure learning approach and learning difficulties. Data collected from 166 Indians and 69 Nepalis were compared. The scores on various scales of the inventory indicate that Nepalis are more fearful and less confident regarding examination and course completion and have significantly less positive perception about academic capability. Indian students scored significantly higher on motivation, interest, and deep processing. The language problem was significantly greater for Nepali students. Higher percentages of Nepalis experienced various academic and nonacademic problems. The study highlights the need to consider difference in learning approach among the students of health science courses that admit students from different academic, nonacademic, and cultural backgrounds.

Analysis of Variance↗
PubMed2001

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

Antigens, CD↗
PubMed2001

Recent developments in computational proteomics.

The mapping of the human genome was completed earlier this year and efforts are underway to understand the role of gene products (i.e. proteins) in biological pathways and human disease and to exploit their functional roles to derive protein therapeutics and protein-based drugs. A key component to the next revolution in the 'post-genomic' era will be the increasingly widespread use of protein structure in rational experimental design. Improvements in quality, availability and utility of large-scale three- and four-dimensional protein structural information are enabling a revolution in rational design, having particular impact on drug discovery and optimization. New computational methodologies now yield modeled structures that are, in many cases, quantitatively comparable with crystal structures, at a fraction of the cost.

Journal Article↗
PubMed2001

Recent developments in computational proteomics.

The mapping of the human genome was completed earlier this year and efforts are underway to understand the role of gene products (i.e. proteins) in biological pathways and human disease and to exploit their functional roles to derive protein therapeutics and protein-based drugs. A key component to the next revolution in the 'post-genomic' era will be the increasingly widespread use of protein structure in rational experimental design. Improvements in quality, availability and utility of large-scale 3D and 4D protein structural information are enabling a revolution in rational design, having particular impact on drug discovery and optimization. New computational methodologies now yield modeled structures that are, in many cases, quantitatively comparable with crystal structures, at a fraction of the cost.

Animals↗
PubMed2000

Sequencing and model structure of a Naja naja atra protein fragment.

We report the amino acid sequence of a basic protein isolated from the snake venom of Naja naja atra. An automated Edman sequencer was used to determine the 65-residue sequence, aided by electrospray ionization/mass spectrometry. Online reduction and pyridylethylation of the peptide was performed to identify the cysteine residues. Trypsin, chymotrypsin and aspartic digestions were carried out to derive peptide fragments for further sequencing. Fragmented peptides were overlapped to obtain the complete sequence. Molecular mass measurements of the whole protein and its fragments were used as a countercheck for sequence assignment. Further confirmation of the sequence was indicated by sequence homology to other snake venom neurotoxins. A molecular model of the tertiary structure was constructed based on sequence homology, and was refined by global minimization and extensive quality control algorithms. Electrostatic and hydrophobic surface calculations and molecular dynamics simulations were carried out to determine the functional properties of the molecule.

Amino Acid Sequence↗
PubMed2000

The bone marrow in Hodgkin's disease--a two year study.

A total of forty bone marrow trephine biopsies and aspirates were studied from thirty five patients suffering from Hodgkin's disease during the two year period 1994 and 1995. Of these twenty five were at the time of diagnosis of the disease and fifteen after treatment. The biopsies were studied for incidence of involvement as well as associated findings in both the positive and negative biopsies. A comparison of the trephine biopsy with marrow aspirate with respect to yield of positivity was made. Five patients (20%) at the time of diagnosis and two (13.33%) after treatment showed involvement of the marrow. None of the seven corresponding aspirates were positive for involvement showing that biopsies were superior to aspirates in detecting marrow infiltration in Hodgkin's disease. Suppression of the marrow, fibrosis and lymphocytic aggregates were the other findings in positive biopsies. Eosinophilia and myelosuppression were notable changes in the negative biopsies. One biopsy also showed granulomas. The probable significance of these findings are also discussed.

Adult↗
PubMed1998

Identification of two new hydrophobic residues on basic fibroblast growth factor important for fibroblast growth factor receptor binding.

Basic fibroblast growth factor (bFGF) is implicated in the pathogenesis of several types of vascular and connective diseases. A key step in the discovery of bFGF receptor antagonists to mitigate these actions is to define the functional epitopes required for receptor binding of the growth factor. Using structure-based site-directed mutagenesis, two critical areas on the bFGF surface for the high affinity receptor binding have already been identified [Springer, B.A., Pantoliano, M.W., Barberal, F.A., Gunyuzlu, P.L., Thompson, L.D., Herblin, W.F., Rosenfeld, S.A. and Book, G.W. (1994) J. Biol. Chem., 269, 26879-26884; Zhu, H.Y., Ramnarayan, K., Anchin, J., Miao, Y., Sereno, A., Millman, L., Zheng, J., Balaji, V.N. and Wolff, M.E. (1995) J. Biol. Chem., 270, 21869-21874; Zhu, H.Y., Anchin, J., Ramnarayan, K., Zheng, J., Kawai, T., Mong, S. and Wolff, M.E. (1997) Protein Engng, 10, 417-421]. According to these studies, one receptor binding site includes two polar residues Glu96 and Asn104 on bFGF whereas the other includes four hydrophobic residues Tyr24, Tyr103, Leu140 and Met142. Using a protein modelling technique, we report here the identification of a new hydrophobic patch on bFGF which includes residues Tyr73, Val88 and Phe93. The role of this area on receptor binding affinity was evaluated by mutating each of these residues individually and determining the mutated protein's (mutein's) receptor binding affinity. In addition, we examined the role of two other hydrophobic residues, Phe30 and Leu138, on bFGF for high-affinity receptor binding. These two residues are the neighbors of the hydrophobic residues Tyr24 and Tyr103, respectively. Replacement of Val88 and Phe93 with alanine reduced the receptor binding affinity about 10- and 80-fold, respectively, compared with wild-type bFGF. In contrast, substitution of Phe30 and Leu138 with alanine has no effect on the receptor binding affinities. We conclude that the newly identified hydrophobic residues, Val88 and Phe93, are crucial for the receptor binding. The present data, together with the previous identification of four hydrophobic residues (Tyr24, Tyr103, Leu140 and Met142), suggests that there are two hydrophobic receptor binding sites on the bFGF surface. Our findings can be employed in the discovery and design of potent bFGF antagonists using computational methods.

Amino Acid Substitution↗
PubMed1997

Analysis of high-affinity binding determinants in the receptor binding epitope of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is implicated in the pathogenesis of several vascular and connective diseases. A key step in the discovery of bFGF receptor antagonists to mitigate these actions is to define the functional epitope required for receptor binding of the growth factor. In previous studies, we identified Glu96 as an essential residue in this epitope using site-directed mutagenesis. Here we examined the role of solvent accessible neighboring residues of Glu96 of bFGF on receptor binding affinity. Wild-type bFGF and its muteins were cloned and expressed in Escherichia coli and evaluated for FGF receptor binding affinity. Replacement of Asn104 of bFGF by alanine reduced receptor binding affinity over 400-fold compared with wild-type bFGF. We next explored the effect of neighboring residues of Asn104 on receptor binding affinity-Muteins in which Arg97, Leu98, Glu99, Asn101, Asn102, Thr105 and Pro141 were individually replaced by alanine exhibited receptor binding similar to wild-type bFGF. By contrast, substitution of Tyr103 or Leu140 by alanine reduced receptor binding affinity about 400- and 150-fold, respectively, in accord with a previous report. We conclude that at least six solvent-accessible residues in bFGF are crucial for high-affinity receptor binding, as evidenced by at least a 10-fold diminution in the affinity of the corresponding alanine muteins. The polar residues Glu96 and Asn104 appear to form an area important for facilitating the initial contact between ligand and receptor, whereas Tyr24, Tyr103, Leu140 and Met142 form a hydrophobic patch that may stabilize the complex. The detailed structure of this functional epitope can be employed in the discovery and design of bFGF antagonists using computational methods.

Asparagine↗
PubMed1995

Glu-96 of basic fibroblast growth factor is essential for high affinity receptor binding. Identification by structure-based site-directed mutagenesis.

The importance of basic fibroblast growth factor (bFGF) in several pathophysiological processes has stimulated interest in the design of receptor antagonists to mitigate such effects. Of key importance in this connection is the characterization of the functional binding epitopes of the growth factor for its receptor. Based on peptide mapping and molecular dynamics calculations of the three-dimensional structure of basic fibroblast growth factor, we employed site-directed mutagenesis to investigate the effect of altering residues at positions 107, 109-114, and 96 on bFGF on receptor binding affinity. All muteins were cloned and expressed in Escherichia coli, purified to homogeneity employing heparin-Sepharose columns, and evaluated for receptor binding affinity. We found that replacement of residues at positions 107 and 109-114 by alanine or phenylalanine had little effect on receptor binding affinities compared with wild type bFGF, in agreement with previous evidence that bFGF residues 109-114 comprise a low affinity binding site. By contrast, substitution of Glu-96 with alanine yielded a molecule having about 0.1% of the affinity of the wild type bFGF. The affinity of the corresponding lysine and glutamine muteins was 0.3 and 10%, respectively, emphasizing the importance of a negative charge at this position. Our findings are consistent with the view that residues 106-115 on bFGF represent a low affinity binding site on bFGF. In addition, we identify Glu-96 as a crucial residue for binding to fibroblast growth factor receptor-1.

Amino Acid Sequence↗
PubMed1995

Conformational studies on model dipeptides of Gly, L-Ala and their C alpha-substituted analogs.

As a part of the development of conformational guidelines for the design of metabolically altered peptidomimetics, we present conformational energy calculations on model dipeptide compounds with glycine (Gly), L-alanine (Ala), alpha-aminoisobutyric acid (Aib), L-tert-butylglycine (Tle), L-phenylglycine (Phg), (alpha, alpha)-diphenylglycine (D phi g), L-2-aminobutyric acid (Abu), 2-amino-2-ethylbutyric acid (Deg), L-2-amino-2-vinylacetic acid (Ava) and (alpha, alpha)-divinylglycine (Dvg). The energy calculations have been made using molecular mechanics methods with a force field derived from MM2. The salient features are expressed in terms of conformational energy plots, drawn as a function of the backbone torsion angles phi(Ci'-1-Ni-Ci alpha i-Ci') and psi(Ni-Ci alpha -C'-N(i+1)). The low-energy structures of these compounds are qualitatively consistent with the X-ray crystal structure analyses of peptides and peptidomimetics. They are also in agreement with the results of the solution-phase studies carried out by NMR and IR techniques. The results obtained have important implications in the design of conformationally restricted peptidomimetics.

Alanine↗