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R Murali

Publications and source records attributed to R Murali.

78 records · Page 5Linked to original sources

Molecular recognition of a peptide mimic of the Lewis Y antigen by an anti-Lewis Y antibody.

Peptides as mimics of carbohydrates display a distinct advantage in vaccine design because of ease of synthesis and their inherent T cell-dependent nature as immunogens. While peptides that mimic carbohydrates have been described, it is not clear how they do so. To further our insight into structural relationships between peptide-mimics and carbohydrate structures, we have analyzed a potential recognition scheme between the murine monoclonal antibody, B3, directed against the tumor-associated antigen Lewis Y oligosaccharide and a peptide identified from phage display screening with B3. The Lewis Y core antigen is a difucosylated structure consisting of four hexose units. The B3 antibody binds to the peptide sequence APWLYGPA in which the putative sequence APWLY is critical for binding to the antibody. Not having experimental structural information for B3, the crystal structure of another anti-Lewis Y antibody, BR96, solved in complex with a nonoate methyl ester Lewis Y tetrasaccharide, provides a molecular basis for LeY antigen recognition and specificity, and how this binding relates to peptide binding. As a guide to place the APWLY motif in the B3 combining site, a fragment library was searched for analogous compounds that have the potential to bind to B3. Our modeling study shows that the B3-peptide complex shares similar recognition features for the difucosylated type 2 lactoseries' structure. This analysis provides a molecular perspective for peptide mimicry of a carbohydrate epitope.

Amino Acid Sequence↗

The hidden code in genomics: a tool for gene discovery.

Among new insights coming from the completion of sequencing of the human genome, reported in Nature and Science, are clues of how evolution has increased the complexity of species, and in particular how the genetic code has enabled this process. It is clear that life has not only evolved by increasing the number of genes, but also by ingeniously evolving an efficient code for expressing diversity in the building blocks (i.e. the amino acids). The rules of nucleic acid base pairing and the classification of amino acids according to hydrophobicity/hydrophilicity relationships define a binary DNA code, which determines the general biophysical characteristics of proteins. Sense and antisense strands can encode protein segments having inverted and complementary hydropathy. The underlying binary code controls association and dissociation of proteins and presumably represents a primordial code that might have emerged in the early stages of self-organizing biochemical cycles. It is the purpose of this communication to provide a perspective of the code in the context of a binary language from its primordial origin to its present day format and to propose to use this code as a genomic mining tool.

Expressed Sequence Tags↗

Dysphonia: a frequently encountered symptom in the evaluation of infants with unobstructed supracardiac total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection is a relatively uncommon congenital cardiac anomaly. When there is obstruction to pulmonary venous drainage or severe pulmonary hypertension due to increased pulmonary blood flow, the patient is usually critically ill and the diagnosis is unambiguous. However, in some patients the symptoms may be mild and often overlap with those of other noncardiac diseases. Tachypnea, failure to thrive, and mild cyanosis are the most frequently reported symptoms. In our patient population, we encountered a frequent observation by parents that the child had an alteration in voice which we elected to refer to as dysphonia for the purpose of this study. We retrospectively reviewed all patients with total anomalous pulmonary venous connection who were evaluated at our institution from January 1996 to January 1999 and found that 27% of patients had dysphonia as a presenting complaint to their primary care provider. We hypothesize that the etiology of this phenomenon lies in the possible compression of the left recurrent laryngeal nerve in the vicinity of the dilated pulmonary artery and the left vertical vein.

Child↗

Pediatric posterior fossa tumors: hazards of the "preoperative" shunt.

Many neurosurgeons recommend a "preoperative" shunt for children with posterior fossa tumors. It has been reported that the definitive surgery is simplified and the postoperative course is more benign as a result of the cerebrospinal fluid diversion. The present report documents complications as a result of upward herniation and hemorrhage within the tumor after shunt placement. On the basis of this experience, we conclude that a shunt is potentially hazardous and should be restricted to that selected group of patients who are acutely ill from increased intracranial pressure that is refractory to temporizing pharmacological management.

Adolescent↗

Pre-operative short-term pulmonary rehabilitation for patients of chronic obstructive pulmonary disease undergoing coronary artery bypass graft surgery.

The role of pre-operative short-term pulmonary rehabilitation in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass graft surgery has been assessed for the first time prospectively. Forty-five patients posted for coronary artery bypass graft surgery were randomised to receive either short-term pulmonary rehabilitation (group I) or no such programme (group II). Patients of both the groups were evenly matched with respect to age, sex, body surface area, duration and severity of chronic obstructive pulmonary disease and coronary artery disease. Normal individuals who evenly matched with the study group were assessed for normal respiratory function parameters. Pre-operative and post-operative peak expiratory flow rate, inspiratory capacity, post-operative ventilation time, post-operative pulmonary complication and hospital stay were determined in both the groups. Peak expiratory flow rate (220.0 +/- 12.9 and 324.3 +/- 84.3 in group I, 218.0 +/- 16.4 and 260.5 +/- 35.2 in group II) and inspiratory capacity (844.0 +/- 147.4 and 1100.0 +/- 158.1 in group I, 830.0 +/- 117.4 and 1090 +/- 137 in group II) were significantly lower before and after surgery respectively in both groups compared to normal values. Even though both groups showed a significant rise in post-operative peak expiratory flow rate and inspiratory capacity after surgery, the post-operative peak expiratory flow rate and inspiratory capacity in group I was significantly higher than in group II. In group I, the post-operative ventilation time (24.5 +/- 6.00 hours), post-operative complications (n = 4) and hospital stay (12.4 +/- 3.6 days) were significantly lower than in group II (35.2 +/- 22.3 hours, n = 11, 18.8 +/- 6.6 days respectively). These data suggest that short-term pulmonary rehabilitation is feasible and effective in improving pulmonary functions before and after surgery and in reducing surgical morbidity and cost of medical care significantly.

Breathing Exercises↗

Systemic lupus erythematosus in Indian patients: prognosis, survival and life expectancy.

BACKGROUND: There have been several studies on survival patterns in Indian patients with systemic lupus erythematosus but it is still not clear as to which factors at diagnosis predict survival outcome. The impact of specific organ involvement, and of disease activity itself, needs to be studied further. METHODS: We conducted a non-concurrent prospective study of 98 lupus patients between 1981 and 1993. The clinical symptoms, signs and investigation results at onset, and at subsequent visits, were abstracted from the case notes. A systemic lupus erythematosus disease activity index (SLEDAI) was constructed at the initial presentation and for each subsequent visit. Patients not attending for at least 6 months were traced by post. The quantitative data from the SLEDAI was used to construct a Markov chain mathematical expression designed to predict life expectancy. RESULTS: The cumulative percentage survival at 1, 5 and 10 years was found to be 89%, 77% and 60%, respectively. The Markov chain predicted a life expectancy of 13.9 years. Central nervous system and renal involvement were poor prognostic factors. Proteinuria (> 0.5 g/day) caused a 50% reduction in life expectancy but increased disease activity at onset did not predispose to a poor outcome. CONCLUSION: The survival of patients with systemic lupus erythematosus continues to be poor. Central nervous system and renal disease indicate a poor outcome. Hence, new treatment strategies must be evolved to improve the survival of such patients.

Female↗