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D Gupta

Publications and source records attributed to D Gupta.

At least 163 records · Page 9Linked to original sources
PubMed1998

External clues to inner malformations.

A malformation is a morphological defect of an organ, or a larger region of the body resulting from an intrinsically abnormal developmental process. In this analysis of 1421 neonatal autopsies performed between 1984 and 1993, 243 (17.1%) cases showed malformations. The data was analysed to find external cues to internal malformations. Twenty three (85%) of the 27 neonates with various facial abnormalities had associated internal malformations in the form of cardiac (n = 11; 40%), renal (n = 7; 25%), or gastrointestinal (n = 3; 11%) abnormalities and diaphragmatic hernia (n = 2). Sixty seven neonates had neural abnormalities. These were associated with cardiac (n = 7; 10%), renal (n = 12; 18%) or gastrointestinal (n = 7; 10%) abnormalities; 43 cases, however, did not have any associated malformations. Renal malformations (n = 66) had highest association with skeletal abnormalities (n = 9; 22%). As many as 45(76%) of the 59 cases with cardiac abnormalities had no external anomalies. Five cases of hypoplastic lungs were seen, all associated with external malformations.

Abnormalities, Multiple↗
PubMed1997

X-ray crystallographic studies of unique cross-linked lattices between four isomeric biantennary oligosaccharides and soybean agglutinin.

Soybean agglutinin (SBA) (Glycine max) is a tetrameric GalNAc/Gal-specific lectin which forms unique cross-linked complexes with a series of naturally occurring and synthetic multiantennary carbohydrates with terminal GalNAc or Gal residues [Gupta et al. (1994) Biochemistry 33, 7495-7504]. We recently reported the X-ray crystal structure of SBA cross-linked with a biantennary analog of the blood group I carbohydrate antigen [Dessen et al. (1995) Biochemistry 34, 4933-4942]. In order to determine the molecular basis of different carbohydrate-lectin cross-linked lattices, a comparison has been made of the X-ray crystallographic structures of SBA cross-linked with four isomeric analogs of the biantennary blood group I carbohydrate antigen. The four pentasaccharides possess the common structure of (beta-LacNAc)2Gal-beta-R, where R is -O(CH2)5COOCH3. The beta-LacNAc moieties in the four carbohydrates are linked to the 2,3-, 2,4-, 3,6-, and 2,6-positions of the core Gal residue(s), respectively. The structures of all four complexes have been refined to approximately 2.4-2.8 A. Noncovalent lattice formation in all four complexes is promoted uniquely by the bridging action of the two arms of each bivalent carbohydrate. Association between SBA tetramers involves binding of the terminal Gal residues of the pentasaccharides at identical sites in each monomer, with the sugar(s) cross-linking to a symmetry-related neighbor molecule. While the 2,4-, 3,6-, and 2,6-pentasaccharide complexes possess a common P6422 space group, their unit cell dimensions differ. The 2, 3-pentasaccharide cross-linked complex, on the other hand, possesses the space group I4122. Thus, all four complexes are crystallographically distinct. The four cross-linking carbohydrates are in similar conformations, possessing a pseudo-2-fold axis of symmetry which lies on a crystallographic 2-fold axis of symmetry in each lattice. In the case of the 3,6- and 2,6-pentasaccharides, the symmetry of their cross-linked lattices requires different rotamer orientations about their beta(1,6) glycosidic bonds. The results demonstrate that crystal packing interactions are the molecular basis for the formation of distinct cross-linked lattices between SBA and four isomeric pentasaccharides. The present findings are discussed in terms of lectins forming unique cross-linked complexes with glycoconjugate receptors in biological systems.

Carbohydrate Conformation↗
PubMed1997

Effect of substituents on the thermodynamics of D-galactopyranoside binding to winged bean (Psophocarpus tetragonolobus) basic lectin.

Isothermal titration calorimetric measurements of the binding of deoxy, fluorodeoxy, and methoxy derivatives of D-galactopyranoside (alpha-D-Gal) to the basic lectin from winged bean Psophocarpus tetragonolobus, WBA I, have been carried out. Each of the ligands binding to WBA I displayed the same stoichiometry of one per subunit (29 kDa) of WBA I. The binding enthalpies for various derivatives are essentially independent of temperature and show complementary changes with respect to binding entropies. Replacement of the hydroxyl group by fluorine or hydrogen on C3 and C4 of the galactopyranoside eliminates binding to the lectin, consistent with C3-OH and C4-OH acting as hydrogen bond donors. The affinity for C2 derivatives of galactose decreases in the order GalNAc > 2MeOGal > 2FGal congruent with Gal > 2HGal, which suggests that both polar and nonpolar residues surround the C2 locus of galactose, consistent with the observed high affinity of WBA I toward GalNAc where the acetamido group at C2 position is probably stabilized by both nonpolar interactions with the methyl group and polar interactions with the carbonyl group. The binding of C6 derivatives follows the order Gal > 6FGal > D-Fuc >> 6MeOGal congruent with L-Ara, indicating the presence of favourable polar interactions with a hydrogen bond donor in the vicinity. On the basis of these results the hydrogen bond donor-acceptor relationship of the complexation of methyl-alpha-D-galactopyranoside with the primary combining site of WBA I is proposed.

Acetylgalactosamine↗
PubMed1997

Thermodynamics of lectin-carbohydrate interactions. Binding of the core trimannoside of asparagine-linked carbohydrates and deoxy analogs to concanavalin A.

The trisaccharide 3,6-di-O-(alpha-D-mannopyranosyl)-D-mannose, which is present in all asparagine-linked carbohydrates, was previously shown by titration microcalorimetry to bind to the lectin concanavalin A (ConA) with nearly -6 kcal mol-1 greater enthalpy change and 60-fold higher affinity than methyl-alpha-D-mannopyranoside (Mandal, D. K., Kishore, N., and Brewer, C. F. (1994) Biochemistry 33, 1149-1156). Similar studies of the binding of a series of monodeoxy derivatives of the alpha(1-3) residue of the trimannoside showed that this arm was required for high affinity binding (Mandal, D. K., Bhattacharyya, L., Koenig, S. H., Brown, R. D., III, Oscarson, S., and Brewer, C. F. (1994) Biochemistry 33, 1157-1162). In the present paper, a series of monodeoxy derivatives of the alpha(1-6) arm and "core" Man residue of the trimannoside as well as dideoxy and trideoxy analogs were synthesized. Isothermal titration microcalorimetry experiments establish that the 3-, 4-, and 6-hydroxyl groups of the alpha(1-6)Man residue of the trimannoside binds to the lectin, along with the 2- and 4-hydroxyl groups of the core Man residue and the 3- and 4-hydroxyl groups of the alpha(1-3)Man residue. Dideoxy analogs and trideoxy analogs showed losses of affinities and enthalpy values consistent with losses in binding of specific hydroxyl groups of the trimannoside. The free energy and enthalpy contributions to binding of individual hydroxyl groups of the trimannoside determined from the corresponding monodeoxy analogs are observed to be nonlinear, indicating differential contributions of the solvent and protein to the thermodynamics of binding of the analogs. The thermodynamic solution data agree well with the recent x-ray crystal structure of ConA complexed with the trimannoside (Naismith, J. H., and Field, R. A. (1996) J. Biol. Chem. 271, 972-976).

Calorimetry↗
PubMed1997

Incidence and recognition of interstitial pulmonary fibrosis in developing countries.

Interstitial pulmonary fibrosis in developing countries is now diagnosed with an increased frequency. Increased awareness and more frequent availability of computed tomography and fiberoptic bronchoendoscopy have helped in making the diagnosis more often. The spectrum of diseases causing pulmonary fibrosis is broadly similar to that seen in the West. Connective tissue disorders such as systemic sclerosis and rheumatoid arthritis and sarcoidosis are more common causes. Idiopathic fibrosis is seen in approximately half the patients. Pneumoconiosis such as silicosis are also important. Diagnosis is often established on the basis of clinical features and radiologic findings alone. Transbronchial lung biopsy is used as a frequent method to make histologic diagnosis. Some of the causes described from India are rather rare. One of the interesting examples included a patient in whom pulmonary fibrosis was related to his ascent to very high altitude. Extreme cold, solar radiation, and other factors complicating low atmospheric oxygen pressure were implicated as causative factors. Lung fibrosis, secondary to exposure to toxic gas (methyl isocyanate), is reported in survivors of the Bhopal gas leakage tragedy of 1984. Serial bronchoalveolar studies have show elevated fibronectin levels and the presence of macrophage-neutrophilic exudate in the lavage fluid.

Developing Countries↗
PubMed1997

Pulmonary sarcoidosis: spirometric correlation with transbronchial biopsy.

We studied the relationship between the histopathology obtained by trans-bronchial lung biopsy (TBLB), and spirometric indices in 28 patients of pulmonary sarcoidosis in whom the diagnosis was confirmed. There was a rough correlation between FVC and the histologic granuloma load, interstitial inflammation and the overall histopathological score. Radiological features did not correlate with either spirometry or histopathology.

Adult↗
PubMed1997

Wegener's presenting as submandibular swelling.

We describe a patient in whom bilateral swelling of submandibular glands was the initial manifestation of limited Wegener's disease. The diagnosis was based on positive anti-neutrophil cytoplasmic antibody [C-ANCA], dense inflammatory infiltrate predominantly of lymphocytes in submandibular glands, presence of non-caseating ill-formed granulomas in transbronchial biopsy and resolution of symptoms following immuno-suppressive treatment.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

500 picosecond molecular dynamics simulation of amphiphilic polypeptide Ac(LKKL)4 NHEt with 1,2 di-mysristoyl-sn-glycero-3-phosphorylcholine (DMPC) molecules.

Molecular dynamics (MD) simulation of the interaction between amphiphilic polypeptide Ac(LKKL)4NHEt and 4 DMPC (1,2 di-mysristoyl-sn-glycero-3-phosphorylcholine) molecules has been carried out at 310 K for 500 picoseconds (ps) using AMBER 4.0. Interaction energy and a number of conformational parameters are calculated for the subaveraged coordinates, using P-CURVES 3.1 and our MD trajectory analysis program ANALMD. No significant change in DMPC headgroup conformation was observed. However, the mobility of P atoms was found to be restricted. The chains were quite flexible and their flexibility increased towards the ends. They interacted amongst themselves. The polypeptide remained predominantly in alpha-helical conformation. Leu1 and Lys2 at the N terminus and Leu13 to Leu16 at C terminus assumed non helical conformation and were quite flexible. Average interaction energy between the polypeptide and DMPC molecules was found to be -151.828 kcal*mol-1. The main contributory factor was electrostatic interaction of Lys NH3+ groups with the DMPC phosphates. On an average one Lys chain interacted with 1.5 DMPC molecules. Central region of the polypeptide had better contact with DMPC molecules. A model for the fusogenic properties of the polypeptide is presented on the basis of MD results.

Amino Acid Sequence↗
PubMed1996

Thermodynamics of carbohydrate binding to galectin-1 from Chinese hamster ovary cells and two mutants. A comparison with four galactose-specific plant lectins.

The thermodynamics of carbohydrate binding to the 14 kDa dimeric beta-galactoside-binding lectin galectin-1 (Gal-1) from Chinese hamster ovary cells and four galactose-specific plant lectins were investigated by isothermal titration microcalorimetry. Recombinant Gal-1 from Escherichia coli, a Cys-->Ser mutant with enhanced stability (C2S-Gal-1), and a monomeric mutant of the lectin (N-Gal-1) were studied along with the soybean agglutinin and the lectins from Erythrina indica, Erythrina crystagalli, and Erythrina corollodendrum. Although the pattern of association constants of the Erythrina lectins was similar for mono- and disaccharides, variations exist in their enthalpy of binding (-delta H) values for individual carbohydrates. While the Erythrina lectins show greater affinities and -delta H values for lactose and N-acetyllactosamine, the soybean agglutinin possesses similar affinities for methyl beta-galactopyranoside, lactose, and N-acetyllactosamine and a greater -delta H value for the monosaccharide. Gal-1 and the plant lectins possess essentially the same affinities for N-acetyllactosamine; however, the animal lectin shows a lower -delta H value and more favorable binding entropy for the disaccharide. While Gal-1, C2S-Gal-1, and N-Gal-1 all possess essentially the same affinities for N-acetyllactosamine, the two mutants possess much lower -delta H values, even though the mutation site(s) are far removed from the carbohydrate binding site. These results indicate that there are different energetic mechanisms of carbohydrate binding between galectin-1, its two mutants, and the Gal-specific plant lectins.

Animals↗
PubMed1996

A comparison of the fine saccharide-binding specificity of Dioclea grandiflora lectin and concanavalin A.

The lectin from the seeds of Dioclea grandiflora (DGL) is a Man/Glc-specific tetrameric protein with physical and saccharide-binding properties reported to be similar to that of the jack bean lectin concanavalin A (ConA). Unlike other plant lectins, both DGL and ConA bind with high affinity to the core trimannoside moiety, 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, which is present in all asparagine-linked carbohydrates. In the present study, hemagglutination inhibition techniques have been used to investigate binding of DGL and ConA to a series of mono- and dideoxy analogs of methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside and to a series of asparagine-linked oligomannose and complex oligosaccharides and glycopeptides. The results indicate that both DGL and ConA recognize epitopes on all three residues of the trimannoside: the 3-, 4-, and 6-hydroxyl groups of the alpha(1-6)Man residue, the 3-hydroxyl group of the alpha(1-3)Man residue, and the 2- and 4-hydroxyl groups of the central Man residue of the core trimannoside. However, unlike ConA, DGL does not bind to biantennary complex carbohydrates. This was confirmed by showing that biantennary complex glycopeptides do not bind to a DGL-Sepharose affinity column. Unlike ConA, DGL does not show enhanced affinity for a large N-linked oligomannose carbohydrate (Man9 glycopeptide) relative to the trimannoside. Thus, DGL and ConA share similar epitope recognition of the core trimannoside moiety. However, they exhibit differences in their fine specificities for larger N-linked oligomannose and complex carbohydrates.

Carbohydrate Conformation↗
PubMed1996

CD14 is a cell-activating receptor for bacterial peptidoglycan.

The hypothesis that CD14 (an endotoxin receptor present on macrophages and neutrophils) acts as a cell-activating receptor for bacterial peptidoglycan was tested using mouse 70Z/3 cells transfected with human CD14. 70Z/3 cells transfected with an empty vector were unresponsive to insoluble and soluble peptidoglycan, as well as to low concentrations of endotoxin. 70Z/3-CD14 cells were responsive to both insoluble and soluble peptidoglycan, as well as to low concentrations of endotoxin, as measured by the expression of surface IgM, activation of NF-kappaB, and degradation of IkappaB-alpha. Peptidoglycan also induced activation of NF-kappaB and degradation of IkappaB-alpha in macrophage RAW264.7 cells. These peptidoglycan-induced effects (in contrast to endotoxin-induced effects) were not inhibited by polymyxin B. Both peptidoglycan- and endotoxin-induced activation of NF-kappaB were inhibited by anti-CD14 mAb. The N-terminal 151 amino acids of CD14 were sufficient for acquisition of full responsiveness to both peptidoglycan and endotoxin, but CD14 deletion mutants lacking four small regions within the N-terminal 65 amino acids showed differentially diminished responses to peptidoglycan and endotoxin. These results identify CD14 as the functional receptor for peptidoglycan and demonstrate that similar, but not identical sequences in the N-terminal 65-amino acid region of CD14 are critical for the NF-kappaB and IgM responses to both peptidoglycan and endotoxin.

Amino Acid Sequence↗
PubMed1996

Sequence of bovine carbonic anhydrase VI: potential recognition sites for N-acetylgalactosaminyltransferase.

Carbonic anhydrases (CAs I-VII) are products of a gene family that encodes seven isoenzymes and several CA-related proteins. We report the cloning and sequencing of the cDNA clones encoding one of these isoenzymes, CA VI, from bovine submaxillary gland. The translated polypeptide consists of 319 amino acids, including a signal peptide (14 amino acids) typical of secreted proteins. The predicted mature protein contains 305 amino acids including a 13-amino-acid C-terminal sequence that is also present in the sheep but absent in human CA VI. The deduced mature bovine protein is 87% and 68% identical to that of sheep and human CA VI, respectively. Active-site residues of the enzyme, as well as the three zinc-binding histidines and the two cysteines involved in an intra-chain disulphide bond, are all conserved in the three species. Two potential Asn-glycosylation sites are also conserved, both of which appear to be glycosylated in sheep and bovine CA VI. Two potential peptide recognition sequences are present in bovine CA VI for the glycoprotein hormone: N-acetylgalactosaminyltransferase (GalNAc-transferase), which is one of the two transferases required to form GalNAc-4-SO4 in bovine CA VI-linked oligosaccharides. Specifically, these two sequences are Asp-Leu-Lys-Met-Lys-Lys and Ile-Thr-Lys-Arg-Lys-Lys. Comparison of these sequences with sheep and human CA VI sequences indicates that distinct glycoforms of CA VI could exist in submaxillary gland from different species.

Amino Acid Sequence↗
PubMed1996

Neoadjuvant chemotherapy in locally advanced breast cancer.

Thirty-eight patients with locally advanced breast cancer (Stage III) were treated over a 3-year period. All patients initially received two cycles of CMF (cyclophosphamide, 100 mg/m2 p.o. d1-14; methotrexate 40 mg/m2 intravenously (i.v.), d1 and d8., 5 Fluorouracil 500 mg/m2 i.v. d1 and d8). They were then subjected to surgery and external beam irradiation to the chest field and drainage areas. Four more cycles of chemotherapy completed the treatment protocol. A response to initial chemotherapy was seen in 75.7% patients, with two patients achieving a complete response. No patient had disease progression while on chemotherapy. Tumor reduction of a degree to allow breast conservation procedures was seen in eight patients. The chemotherapy was well tolerated. Twelve patients failed to complete the treatment protocol. Follow-up for the remaining 26 ranges from 9-40 months (mean 18 months). Ten patients developed a recurrence. Of those, only one had isolated local recurrence, two had local and systemic recurrence, and seven had systemic disease alone. Patients with recurrence were salvaged with further chemotherapy (Adriamycin and cyclophosphamide).

Alopecia↗
PubMed1996

Cellular immune responses of patients with juvenile chronic arthritis to retinal antigens and their synthetic peptides.

The objective of this study was to determine the proliferative responses of peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides M and G of S-antigen, yeast histone H3 peptide 106-121 homologous to peptide M and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative response of peripheral blood lymphocytes from 41 patients with JCA (10 with and 31 without uveitis) and 23 healthy controls against the above antigens. The responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA patients with and without uveitis, respectively, responded (stimulation index > 3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or R16 of IRBP. None of the healthy controls responded to any of these antigens. The difference in the frequency of responders (SI > 3) between JCA associated with uveitis and healthy controls was statistically significant (p = 0.001). Similarly, the difference between JCA with and without uveitis was also significant (p = 0.013). Our findings suggest that these antigens may have a role in the pathogenesis of uveitis in a subset of patients with JCA.

Amino Acid Sequence↗
PubMed1996

Molecular dynamics simulation of conformational flexibility of alamethicin fragments in aqueous and membranous environment.

We present here results on molecular dynamics (MD) simulation on two fragments of channel forming antibiotic peptide Alamethicin, containing isoamino butyric acid (Aib). Simulations are carried out in aqueous and membranous environment in a bilayer of 39 molecules of Dimyristoyl phosphatidyl choline (DMPC). The peptides Boc-Pro-Aib-Ala-Aib-OBzl (Alam 1) and Boc-Leu-Aib-Pro-OBzl (Alam 2) were simulated from their crystallographic coordinates. The bilayers were built from two different conformations (A and B) of DMPC reported in crystal data. The P-N dipoles were arranged hexagonally with surface area per lipid molecule 66.5 A degrees 2 and P-P separation across the bilayer 34 A degrees. They were hydrated by 28.6 and 25.5 water molecules per DMPC molecule. Simulations are done using AMBER 4.0 package in constant number volume temperature (NVT) condition for 100 pico seconds (ps) in aqueous environment and 250 ps of equilibrated bilayer. Geometric parameters of lipids as: bilayer thickness, order parameter of the chains, transfraction of chain torsional angles were monitored. We also monitored geometric parameters of the peptides as backbone torsional angles, distances amongst C alpha atoms, angles between C alpha atoms, movement of center of gravity (CG) along and perpendicular to bilayer normal. We find that membrane bilayer is slightly disturbed due to the presence of peptides. In case of alam 2 in water angles phi 1 and phi 3 showed larger variation in water compared to same in the bilayer. The peptide conformation is more stable in DMPC bilayer. However the peptides showed movement along and perpendicular to bilayer normal. This we believe is due to hydrophobic nature of these peptides.

Alamethicin↗
PubMed1996

Comparative cross-linking activities of lactose-specific plant and animal lectins and a natural lactose-binding immunoglobulin G fraction from human serum with asialofetuin.

Plant and animal lectins bind and cross-link certain multiantennary oligosaccharides, glycopeptides, and glycoproteins. This can lead to the formation of homogeneous cross-linked complexes, which may differ in their stoichiometry depending on the nature of the sugar receptor involved. As a precisely defined ligand, we have employed bovine asialofetuin (ASF), a glycoprotein that possesses three asparagine-linked triantennary complex carbohydrate chains with terminal LacNAc residues. In the present study, we have compared the carbohydrate cross-linking properties of two Lac-specific plant lectins, an animal lectin and a naturally occurring Lac-binding polyclonal immunoglobulin G subfraction from human serum with the ligand. Quantitative precipitation studies of the Lac-specific plant lectins, Viscum album agglutinin and Ricinus communis agglutinin, and the Lac-specific 16 kDa dimeric galectin from chicken liver demonstrate that these lectins form specific, stoichiometric cross-linked complexes with ASF. At low concentrations of ASF, 1:9 ASF/lectin (monomer) complexes formed with both plant lectins and the chicken lectin. With increasing concentrations of ASF, 1:3 ASF/lectin (monomer) complexes formed with the lectins irrespective of their source or size. The naturally occurring polyclonal antibodies, however, revealed a different cross-linking behavior. They show the formation of 1:3 ASF/antibody (per Fab moiety) cross-linked complexes at all concentrations of ASF. These studies demonstrate that Lac-specific plant and animal lectins as well as the Lac-binding immunoglobulin subfraction from specific stoichiometric cross-linked complexes with ASF. These results are discussed in terms of the structure-function properties of multivalent lectins and antibodies.

Animals↗
PubMed1996

Differential activation of extracellular signal-regulated kinase (ERK) 1, ERK2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases by bacterial peptidoglycan.

Soluble staphylococcal peptidoglycan (sPGN) is an inducer of cytokine secretion and may activate macrophages through the CD14 lipopolysaccharide (LPS) receptor. To elucidate sPGN-activated signal transduction pathways, stimulation of mitogen-activated protein (MAP) kinases by sPGN was studied in mouse RAW264.7 macrophages. sPGN strongly activated extracellular signal-regulated kinase (ERK) 1 and ERK2, moderately activated c-Jun NH2 terminal kinase (JNK), and weakly activated p38 MAP kinase, in contrast to LPS, which strongly activated all of these kinases, and phorbol 12,13-dibutyrate (PDB), which strongly activated ERK1 and ERK2 but did not activate p38 or JNK. sPGN- and LPS-induced activation of ERK1 and ERK2, unlike PDB-induced activation, was sensitive to inhibition by herbimycin A and insensitive to inhibition by increased intracellular cAMP. These results demonstrate differential activation of MAP kinases by sPGN, similar but not identical activation of signal transduction pathways by sPGN and LPS, and different mechanisms of MAP kinase activation by bacterial stimulants and phorbol esters.

1-Methyl-3-isobutylxanthine↗