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Biomedical subjects

D Gupta

Publications and source records attributed to D Gupta.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

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↗

Fast breathing in the diagnosis of pneumonia--a reassessment.

In this hospital-based prospective study, a total of 222 children presenting with cough and/or breathlessness were screened for presence of lower respiratory infection. All clinically-detected cases of LRI and every fifth case of URI were investigated. Pneumonia was defined as presence of abnormal shadows on chest roentgenograms, against which the clinical symptoms and signs were assessed for their utility in the diagnosis of pneumonia. Fast breathing was found to be the most useful sign predicting pneumonia in all age groups. Cut-off points at 50 breaths/min for infants including neonates, 40 breaths/min for children aged 12-35 months, and 30 breaths/min for children aged 36-60 months indicated presence of pneumonia. Crepitations on auscultation of chest was found to have good correlation with presence of radiological pneumonia. Other signs like chest indrawing and cyanosis were found to be highly specific signs in detecting pneumonia, but had low sensitivity.

Age Factors↗

Bronchial responsiveness of non-smoking women exposed to environmental tobacco smoke or biomass fuel combustion.

We studied bronchial responsiveness (BR) in three groups of housewives with or without history of exposure to tobacco smoke or combustion of biomass fuels. Methacholine bronchoprovocation test was used to study BR. The group I subjects (60), who served as controls, were nonsmokers and had no chronic exposure to passive smoking or environmental tobacco smoke (ETS) or biomass fuels. Three of these women showed a 20 per cent FEV1 fall with a cumulative methacholine dose of 72.5 mg or less. Of 60 women in group II (ETS-exposure) and 52 in group III (biomass exposure), 26 (43.3%) and 10 (19.2%) respectively showed bronchial hyper-responsiveness (BHR). The odds ratios for BHR in groups II and III were 14.53 and 4.52 respectively. The number of hyper-responders was significantly more and the mean PD20 less in the exposed than the non-exposed groups. The occurrence of BHR in the ETS exposed group was more (P < 0.05) than the biomass combustion group. There were more hyper-responders (both groups II and III) amongst those who had an exposure index (EI) of 50 or more compared to those with EI of less than 50. We conclude that chronic cumulative exposure to both ETS and biomass combustion produces significant BHR. Further, BHR developed more often on ETS exposure, and when the exposure was present for a longer period.

Adult↗

Splenic lymphocytes with circulating villous lymphocytes--a case report.

A 25 years old male presented with hepatomegaly splenomegaly and fever. He was diagnosed as splenic lymphoma with circulating villous lymphocytes (SLVL) on morphology, cytochemistry and immunocytochemistry performed on peripheral blood and bone marrow smears. Case is being presented because of rarity and unusual presentation at young age.

Adult↗

Peptidoglycan induces transcription and secretion of TNF-alpha and activation of lyn, extracellular signal-regulated kinase, and rsk signal transduction proteins in mouse macrophages.

In soluble peptidoglycan (PGN) from staphylococcal cell walls as well as soluble PGN (sPGN) secreted by staphylococci in the presence of beta-lactam antibiotics induced TNF-alpha mRNA and secretion of bioactive TNF-alpha in the murine RAW264.7 macrophage cell line, PGN and sPGN also induced rapid and dose-dependent tyrosine phosphorylation of several cellular proteins, including lyn and mitogen-activated protein kinases (extracellular signal-regulated kinases; but not hck, fgr, or vav) and increased the activities of mitogen-activated protein and rsk kinases. These PGN- and sPGN-induced effects were qualitatively similar to the effects induced by ReLPS, but higher concentrations of PGN and sPGN than ReLPS were required. In contrast to the ReLPS-induced effects, the PGN- and sPGN-induced effects were not inhibited by polymyxin B. All PGN-, sPGN-, and ReLPS-induced effects were serum independent, since they were observed both in RAW264.7 cells grown and stimulated in the presence of serum and in the cells adapted to growth and stimulated in a serum- and albumin-free medium. These results indicate that lyn, extracellular signal-regulated kinase, and rsk signal transduction molecules may be involved in macrophage activation by PGN and further support the idea that PGN and LPS may activate the cells through similar mechanisms.

Animals↗

X-ray crystal structure of the soybean agglutinin cross-linked with a biantennary analog of the blood group I carbohydrate antigen.

Soybean agglutinin (SBA) (Glycine max), which is a tetrameric GalNAc/Gal-specific lectin, has recently been reported to form unique, highly organized cross-linked complexes with a series of naturally occurring and synthetic multiantennary carbohydrates with terminal GalNAc or Gal residues [Gupta, D., Bhattacharyya, L., Fant, J., Macaluso, F., Sabesan, S., & Brewer, C. F. (1994) Biochemistry 33, 7495-7504]. In order to elucidate the nature of these complexes, the X-ray crystallographic structure of SBA cross-linked with a biantennary analog of the blood group I carbohydrate antigen is reported. The structure reveals that lattice formation is promoted uniquely by the bridging action of the bivalent pentasaccharide (beta-LacNAc)2Gal-beta-R, where R is -O(CH2)5COOCH3 and the beta-LacNAc moieties are linked to the 2 and 6 positions of the core Gal. The structure of SBA complexed with the synthetic biantennary pentasaccharide has thus been determined by molecular replacement techniques and refined at 2.6 A resolution to an R value of 20.1%. The crystals are hexagonal with a P6(4)22 space group, which differs significantly from that of crystals of the free protein. In the structure, each monomeric asymmetric unit contains a Man9 oligomannose-type chain at Asn 75, with only the first two GlcNAc residues visible. The overall tertiary structure of the SBA subunit is similar to that of other legume lectins as well as certain animal lectins. However, the dimer interface in the SBA tetramer is unusual in that only one complete peptide chain is sterically permitted, thus requiring juxtapositioning of one C-terminal fragmented subunit together with an intact subunit. Association between SBA tetramers involves binding of the terminal Gal residues of the pentasaccharide at identical sites in each monomer, with the sugar cross-linking to a symmetry-related neighbor molecule. The cross-linking pentasaccharide is in a conformation that possesses a pseudo-2-fold axis of symmetry which lies on a crystallographic 2-fold axis of symmetry of the lattice. Hence, the symmetry properties of the bivalent oligosaccharide as well as the lectin are structural determinants of the lattice. The results are discussed in terms of multidimensional carbohydrate-lectin cross-linked complexes, as well as the signal transduction properties of multivalent lectins.

Binding Sites↗

Cardiac surgery and cold-reactive proteins.

Cold agglutinins are commonly found in sera of healthy persons. They rarely become clinically apparent due to their activity at low temperatures. In these patients, cardiovascular operations requiring hypothermia can result in complications such as hemolysis, renal failure, and myocardial damage and can cause unexpected morbidity and mortality. The literature on cold-reactive proteins is reviewed, and methods of diagnosis and management related to cardiac surgery are suggested. Ideally all patients should be routinely tested preoperatively for the antibodies, and appropriate changes in cardiopulmonary bypass and myocardial management plans should be made in positive patients. Preoperative plasmapheresis may be a useful adjunct, especially in patients requiring operation under profound hypothermia and circulatory arrest. Currently, warm heart surgery appears to be the most expedient method. Unexpected detection of agglutination during operation or hemolysis after operation requires a specific treatment plan.

Agglutinins↗

Spinal cord dynorphin precursor intermediates decline during late gestation.

This laboratory has previously reported that the maternal opioid analgesia associated with pregnancy and parturition is mediated, at least in part, by a maternal spinal cord dynorphin/kappa opioid system. This analgesia is accompanied by an increase in dynorphin peptides (1-17 and 1-8) in the lumbar spinal cord. Levels of trypsin-generated arginine6-leucine-enkephalin (Leu-Enk-Arg)-immunoreactive determinants were also determined and used to reflect the content of dynorphin precursor intermediates. In spinal tissue, the amount of dynorphin A (1-17) contained in the form of precursor is, at a minimum, 10-fold higher than the content of mature dynorphin A (1-17) or dynorphin (1-8). During gestational day 22, the content of dynorphin precursor is reduced significantly (approximately 50%). The decline in the magnitude of dynorphin precursor intermediates in the spinal cord of pregnant rats vastly exceeds the magnitude of increase in the content of dynorphin peptides (1-17 and 1-8). This difference can best be explained by postulating a corresponding increase in the rate of release of spinal cord dynorphin (1-17). It is suggested that enhanced processing of dynorphin precursor intermediates represents the initial biochemical level of adaptation of spinal dynorphin neurons to increased demands of pregnancy.

Analgesia↗

Anaesthetic management of acute puerperal uterine inversion.

We identified 18 cases of acute puerperal uterine inversion after vaginal delivery out of 65,581 deliveries in two university-affiliated hospitals (an incidence of 1:3643). In all cases manual repositioning of the uterus without tocolysis was attempted. In four cases this was successful. Of the 14 patients requiring tocolysis, a single dose of terbutaline 0.25 mg i.v. was tried in eight and was successful in five cases (success rate of 63%), while in three patients general anaesthesia was required. In six other patients, general anaesthesia was chosen as the initial management. There was no associated maternal mortality or morbidity with the exception of one case of acute postpartum endometritis. We suggest that when tocolysis is required, terbutaline should be used first because of its rapid onset of action, short duration, simplicity, availability in the labour suite and familiarity to the obstetrician, and general anaesthesia, with its inherent dangers, if possible, should be avoided.

Acute Disease↗

Analysis of donor-deferral pattern in a voluntary blood donor population.

A retrospective analysis of records of the deferred donors from 1 October 1992 to 31 December 1993 was performed. Of 14,269 prospective blood donors (13,030 males and 1,239 females), 2,431 (16.4%) donors were disqualified for various reasons: 8.1% of the donors were deferred for non-pathological causes while 91.9% were deferred for medical reasons. The most common cause for non-pathological deferral was volunteers attending below the minimum acceptable age (5.2%). Abnormal findings on physical examination accounted for 57.2% of the deferrals in which low body weight was the most common finding (32.3%) followed by low Hb (18.6%). A past history of jaundice was the leading cause for deferral on medical interview. Numerous prospective donors are currently being deferred based on empirically derived criteria. By developing strategies to identify and rationalize donor selection criteria, the blood transfusion services should be able to decrease unnecessary deferrals.

Adolescent↗

Magnetic resonance appearance of tuberculosis of the knee joint with ruptured Baker's cyst.

After the spine, the knee joint is the most commonly affected joint in skeletal tuberculosis. Baker's cyst is a rather rare complication of knee joint tuberculosis. The plain radiographic appearance of the tuberculous knee joint has been amply described. We present the magnetic resonance appearance of a tuberculous knee joint associated with a ruptured popliteal cyst.

Biopsy, Needle↗