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Biomedical subjects

R Malhotra

Publications and source records attributed to R Malhotra.

At least 91 records · Page 5Linked to original sources
PubMed1998

P-selectin binds to bacterial lipopolysaccharide.

Multiple organ failure associated with disseminated intravascular coagulation is a frequent complication in septic shock patients. Accumulation of platelets and neutrophils in the organs contributes to the manifestation of lipopolysaccharide (LPS)-induced organ failure. Although a direct interaction between LPS and platelets is well documented, the nature of the surface receptor for LPS on platelets is unknown. In this article we show that P-selectin is a receptor for LPS. The binding of LPS to P-selectin is independent of Ca2+, and is blocked by antibodies to P-selectin, lipid A and fucoidan. Platelets pre-treated with thrombin showed fourfold higher binding of fluorescein isothiocyanate (FITC)-conjugated LPS compared to untreated platelets and the binding of FITC-conjugated LPS to platelets was blocked in the presence of anti-P-selectin antibodies. It is likely that the binding of LPS via P-selectin on activated platelets or epithelium could have a significant role in the pathophysiology of organ failure in septic shock.

Blood Platelets↗
PubMed1998

Subtalar arthrodesis for flexible hindfoot deformities in children.

Flexible hindfoot valgus deformities in 16 patients (20 feet) with poliomyelitis and 10 patients (16 feet) with cerebral palsy were surgically treated by a modified Dennyson-Fulford operation using a fibular dowel and a screw. The correction achieved was assessed clinically and radiologically after a mean follow-up of 3.6 years. Overall good results were achieved in 86%. There were no cases of under- or over-correction, pseudarthrosis or screw failure. The procedure is suitable even for spastic planovalgus deformities. Complications related to screw position can be avoided by following the recommendations given here. Use of fluoroscopy and cannulated screws facilitate quick and easy completion of the procedure.

Arthrodesis↗
PubMed1998

Laparoscopic management of cystic disease of the liver.

BACKGROUND: Laparoscopic management of cystic disease of the liver, including severe polycystic disease, is evolving. METHODS: Wide unroofing, or "fenestration," as is required for a successful result in open cases, leads to complete resolution of the cysts. This can even occur in chronic cysts, with wide-enough unroofing, given time. RESULTS: In polycystic disease, adequate fenestration of superficial, cysts allows deeper cysts to prolapse and be similarly fenestrated, thus reducing pressure effects on the liver and restoring normal function. CONCLUSION: However, because of the distortion of anatomy by this disease, it is important that an experienced liver surgeon perform such a complex procedure, as operative complications could be severe.

Adult↗
PubMed1998

Interaction of C1q and the collectins with the potential receptors calreticulin (cC1qR/collectin receptor) and megalin.

Several proteins have been identified as candidate cell-surface receptors for the complement protein C1q. Some of these also interact with the structurally-related collectin proteins. Previous descriptions of C1q-binding properties of cells, and information on the cellular distribution of candidate receptors suggest that there is more than one physiologically relevant receptor for C1q. Two such candidate receptors, cell-surface calreticulin (also referred to as cC1qR or collectin receptor) and megalin are discussed in this review.

Amino Acid Sequence↗
PubMed1998

Comparison of the cardiovascular effects of 2.5% phenylephrine and 10% phenylephrine during ophthalmic surgery.

PURPOSE: The recommended concentration of topical phenylephrine for mydriasis is still a matter of debate. Our purpose was to compare the cardiovascular effects of 10% and 2.5% topical aqueous phenylephrine. METHODS: We carried out a double-masked randomised study on 54 consecutive patients undergoing routine local anaesthetic cataract extraction, comparing the effects on blood pressure and heart rate of either 2.5% or 10% topical aqueous phenylephrine in combination with 1% topical aqueous tropicamide in those with no history of cardiovascular disease. RESULTS: No difference was found in the rise in blood pressure produced by 2.5% and 10% topical aqueous phenylephrine. We also found no sustained changes in blood pressure or heart rate after instillation of either 2.5% or 10% topical aqueous phenylephrine. CONCLUSION: We recommend the routine use of 2.5% topical aqueous phenylephrine as a mydriatic agent during cataract surgery and acknowledge the role of 10% topical aqueous phenylephrine as an effective mydriatic agent in cases where 2.5% phenylephrine may not be so effective, such as in subjects with darkly pigmented irides.

Aged↗
PubMed1998

Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries.

Antisense experiments are often complicated by the lack of reliable methods for selecting effective antisense sequences. Chimeric oligodeoxynucleotide (ODN) libraries and ribonuclease H (RNase H) were used to identify regions on the 1253 nucleotide angiotensin type-1 receptor (AT1) mRNA that are accessible to hybridization with antisense ODNs. Phosphorothioate antisense ODNs targeted against accessible sites reduced AT1 receptor levels by at least 50% in cell culture. ODNs to 4 sites produced a 70% to 80% reduction. In contrast, most sequences targeted between accessible sites were ineffective. When injected into the brains of rats, ODNs targeted to accessible sites reduced AT1 (by 65%) but not AT2 receptor levels. Additionally, AT1 receptor function as measured by agonist-induced water intake, was significantly attenuated in these rats. ODNs directed between accessible sites were ineffective at suppressing water intake. RNA mapping can be applied to any RNA target to facilitate selection of multiple, active antisense sequences for cell culture and in vivo experiments.

Animals↗
PubMed1998

Characterization of E-selectin-binding epitopes expressed by skin-homing T cells.

The glycoprotein counter-receptors for E-selectin borne on skin-homing T cells are poorly defined. In this study we have used flow cytometry to investigate the surface expression of potential carbohydrate ligands for E-selectin on HUT78, a skin-homing cutaneous T-cell lymphoma. These cells possessed high surface expression of the KM-93 epitope but not HECA 452 or CSLEX1 epitopes. The KM-93 antibody also blocked the binding of HUT78 cells to E-selectin. All these antibodies are reported to recognize sialyl Lewis X (sLex)-like molecules. Using an E-selectin affinity matrix, the main glycoprotein isolated from HUT78 cells was a molecular species of 90 000 MW. Other minor species of molecular weights 40 000, 60 000, 100 000, 120 000 and 200 000 were also identified as potential counter-receptors for E-selectin. Four of the purified counter-receptors (90 000, 100 000, 120 000 and 200 000 MW) stained positive with the KM-93 antibody. Immunoblot analysis of these purified glycoproteins established the identity of the 90 000 MW glycoprotein as l-selectin. Furthermore, an anti-l-selectin antibody inhibited the binding of HUT78 cells to E-selectin, probably by steric inhibition of the carbohydrate ligand for E-selectin that is borne on the C-type lectin domain of l-selectin. These results suggest that a carbohydrate epitope on l-selectin may act as a ligand for E-selectin on skin-homing T cells.

Antibodies, Monoclonal↗
PubMed1998

Trapezius transfer for deltoid paralysis.

We have reviewed 26 patients treated by trapezius transfer for deltoid paralysis due to brachial plexus injury or old poliomyelitis. We assessed the power of shoulder abduction and the tendency for subluxation. There were good results in 16 patients (60%); five were fair and five poor. Trapezius transfer appears to give reasonable results in the salvage of abductor paralysis of the shoulder.

Adolescent↗
PubMed1998

Human lung surfactant protein A exists in several different oligomeric states: oligomer size distribution varies between patient groups.

BACKGROUND: Lung surfactant protein A (SP-A) is a complex molecule composed of up to 18 polypeptide chains. In vivo, SP-A probably binds to a wide range of inhaled materials via the interaction of surface carbohydrates with the lectin domains of SP-A and mediates their interaction with cells as part of a natural defense system. Multiplicity of lectin domains gives high-affinity binding to carbohydrate-bearing surfaces. MATERIALS AND METHODS: Gel filtration analyses were performed on bronchoalveolar lavage (BAL) fluid samples from three patient groups: pulmonary alveolar proteinosis (n = 12), birch pollen allergy (n = 11), and healthy volunteers (n = 4). Sucrose density gradient centrifugation was employed to determine molecular weights of SP-A oligomers. SP-A was solubilized from the lipid phase to compare oligomeric state with that of water soluble SP-A. RESULTS: SP-A exists as fully assembled complexes with 18 polypeptide chains, but it is also consistently found in smaller oligomeric forms. This is true for both the water- and lipid-soluble fractions of SP-A. CONCLUSION: The three patient groups analyzed show a shift towards lower oligomeric forms of SP-A in the following sequence: healthy-pulmonary alveolar proteinosis-pollen allergy. Depolymerization would be expected to lead to loss of binding affinity for carbohydrate-rich surfaces, with loss or alteration of biological function. While there are many complex factors involved in the establishment of an allergy, it is possible that reduced participation of SP-A in clearing a potential allergen from the lungs could be an early step in the chain of events.

Allergens↗
PubMed1997

Regulation of calcium-induced exocytosis from gastric chief cells by protein phosphatase-2B (calcineurin).

The molecular mechanisms whereby calcium stimulates secretion are uncertain. In the present study, we used streptolysin O (SLO)-permeabilized chief cells from guinea pig stomach to investigate whether protein phosphatase-2B (calcineurin), a calcium/calmodulin-dependent, serine/threonine phosphatase plays a role in mediating calcium-induced pepsinogen secretion. Preincubation of cells with alpha-naphthylphosphate, a non-specific phosphatase inhibitor, decreased calcium-induced secretion. Likewise, specific inhibitors of protein phosphatase-2B (cyclosporin-A and FK-506) caused a dose-dependent reduction in calcium-induced pepsinogen secretion. Moreover, in intact cells, cyclosporin-A and FK-506 inhibited pepsinogen secretion caused by cholecystokinin, carbamylcholine and A23187, agonists known to increase chief cell cytosolic calcium. Okadaic acid, an inhibitor of protein phosphatase-1 and -2A, had no effect on secretion caused by these agonists. Chief cell calcium-dependent phosphatase activity, measured using radiolabeled casein as substrate, was reduced selectively by inhibitors of protein phosphatase-2B. Endogenous substrates for calcium/calmodulin-dependent phosphatase activity were identified by analyzing chief cell lysates using 2-dimensional gel electrophoresis. Increasing the cytosolic calcium concentration resulted in dephosphorylation of a 55-kDa, acidic cytoskeletal protein. FK-506 inhibited dephosphorylation of this protein. Thus, in permeabilized chief cells, specific inhibitors of protein phosphatase-2B inhibit calcium-induced pepsinogen secretion, calcium/calmodulin-dependent phosphatase activity and calcium-induced dephosphorylation of a 55-kDa, acidic cytoskeletal protein. These results support the hypothesis that protein phosphatase-2B (calcineurin) plays an important role in mediating calcium-induced exocytosis.

Animals↗
PubMed1997

Expression and phosphorylation of a MARCKS-like protein in gastric chief cells: further evidence for modulation of pepsinogen secretion by interaction of Ca2+/calmodulin with protein kinase C.

In gastric chief cells, agents that activate protein kinase C (PKC) stimulate pepsinogen secretion and phosphorylation of an acidic 72-kDa protein. The isoelectric point and molecular mass of this protein are similar to those for a common PKC substrate; the MARCKS (for Myristoylated Alanine-Rich C Kinase Substrate) protein. We examined expression and phosphorylation of the MARCKS-like protein in a nearly homogeneous suspension of chief cells from guinea pig stomach. Western blotting of fractions from chief cell lysates with a specific MARCKS antibody resulted in staining of a myristoylated 72-kDA protein (pp72), associated predominantly with the membrane fraction. Using permeabilized chief cells, we examined the effect of PKC activation (with the phorbol ester PMA), in the presence of basal (100 nM) or elevated cellular calcium (1 microM), on pepsinogen secretion and phosphorylation of the 72-KDa MARCKS-like protein. Secretion was increased 2.3-, 2.6-, and 4.5-fold by incubation with 100 nM PMA, 1 microM calcium, and PMA plus calcium, respectively. A PKC inhibitor (1 microM CGP 41 251) abolished PMA-induced secretion, but did not alter calcium-induced secretion. This indicates that calcium-induced secretion is independent of PKC activation. Chief cell proteins were labeled with 32P-orthophosphate and phosphorylation of pp72 was detected by autoradiography of 2-dimensional polyacrylamide gels. In the presence of basal calcium, PMA (100 nM) caused a > two-fold increase in phosphorylation of pp72. Without PMA, calcium did not alter phosphorylation of pp72. However, 1 microM calcium caused an approx. 50% attenuation of PMA-induced phosphorylation of pp72. Experiments with a MARCKS "phosphorylation/calmodulin binding domain peptide" indicated that calcium/calmodulin inhibits phosphorylation of pp72 by binding to the phosphorylation/calmodulin binding domain and not by inhibiting PKC activity. These observations support the hypothesis that, in gastric chief cells, interplay between calcium/calmodulin binding and phosphorylation of a common domain on the 72-kDa MARCKS-like protein plays a role in modulating pepsinogen secretion.

Animals↗
PubMed1997

Depletion of the Outer Asteroid Belt

During the early history of the solar system, it is likely that the outer planets changed their distance from the sun, and hence, their influence on the asteroid belt evolved with time. The gravitational influence of Jupiter and Saturn on the orbital evolution of asteroids in the outer asteroid belt was calculated. The results show that the sweeping of mean motion resonances associated with planetary migration efficiently destabilizes orbits in the outer asteroid belt on a time scale of 10 million years. This mechanism provides an explanation for the observed depletion of asteroids in that region.

Journal Article↗
PubMed1997

L-selectin: a novel receptor for lipopolysaccharide and its potential role in bacterial sepsis.

The activation of leukocytes by bacterial cell wall lipopolysaccharide (LPS) contributes to the pathogenesis of septic shock. It is well established that, in the presence of plasma LPS-binding protein (LBP), LPS binds with high affinity to CD14. The binding of LPS to CD14 has been associated with the activation of cells, although available evidence indicates that CD14 itself does not transduce intracellular signalling. The physiological function of this interaction is to promote host defense mechanisms of cells to combat the infection and clear LPS from the circulation. At higher concentrations of LPS, however, the activation of cells can take place in the absence of LBP and CD14, presumably through a distinct low-affinity signalling LPS receptor. On the evidence published by us and others, we propose that in neutrophils, and possibly other leukocytes, L-selectin can act as a low-affinity LPS receptor.

Animals↗