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Biomedical subjects

R Malhotra

Publications and source records attributed to R Malhotra.

At least 145 records · Page 8Linked to original sources
PubMed1993

Localization of the receptor-binding site in the collectin family of proteins.

Collectin receptor (Clq receptor) has been shown to bind human Clq, mannose-binding protein (MBP), lung surfactant protein A (SP-A) and bovine conglutinin. These ligands have a similar ultrastructure, each consisting of collagenous and globular domains, but do not show a high degree of sequence similarity. For Clq and SP-A, it has been shown that both bind to cell-surface-expressed receptor(s) via their collagenous regions and this is likely to be the case with the other ligands. Within the collagenous region, near the 'bend' region of the collagen triple helix in Clq, MBP and SP-A, a cluster of similar charged residues is observed. This region has been suggested to be associated with receptor binding. A similar region of charge density occurs close to the N-terminus of conglutinin. In this paper we describe a truncated form of conglutinin, which has 55 amino acids missing from the N-terminus and does not bind to the collectin receptor. The results presented here strongly indicate that receptor-ligand interaction is mediated via the N-terminal region of conglutinin, consistent with the earlier proposal for the binding site.

Amino Acid Sequence↗
PubMed1993

Isolation of a human endothelial cell C1q receptor (C1qR).

C1q binding to endothelial cells has been described previously, but the putative cell surface receptor(s) has not been identified. In the present study, modifications of a reported purification of lymphocyte C1q receptor (C1qR) were used to isolate C1q binding sites from human umbilical vein endothelial cells. Cells were harvested, without protease treatment, at passage 10-17 and lysed with 1% Triton X-100. The lysate was fractionated on Fast-performance liquid chromatography (FPLC) Mono-Q using a linear NaCl gradient, followed by high-performance liquid chromatography (HPLC) ion exchange (TSKgel DEAE-NPR). A major protein was eluted that had the same mobility on sodium dodecyl sulfate-polyacrylamide gels and the same NH2-terminal sequence as lymphocyte C1qR. This protein was expressed on the surface, as judged by surface radioiodination, bound to C1q-coated surfaces, and was recognized by polyclonal antilymphocyte C1qR antibodies. Thus, endothelial cells express a C1q receptor that appears identical to lymphocyte C1qR. The data further support the hypothesis that cell surface C1qRs identified on a variety of somatic and cultured cells are either identical or constitute a family of closely related molecules.

Amino Acid Sequence↗
PubMed1993

Pollen grains bind to lung alveolar type II cells (A549) via lung surfactant protein A (SP-A).

Lung surfactant protein A (SP-A) is the most abundant surfactant-associated protein present in the lung. A receptor for SP-A has been shown to be present on A549 alveolar type II cells and on other cell types, including alveolar macrophage. The SP-A receptor on A549 cells has been identified as the collection receptor, or C1q receptor, which binds several structurally-related ligands. SP-A contains C-type lectin domains, but the role of carbohydrate binding by SP-A in physiological and pathological phenomena is not yet established. In this paper we report the binding of SP-A to pollen from Populus nigra italica (Lombardy Poplar), Poa pratensis (Kentucky blue grass), Secale cerale (cultivated rye) and Ambrosia elatior (short ragweed). Saturable and concentration dependent binding of SP-A to pollen grains was observed. Interaction of SP-A with pollen grains takes place through water-extractable components, in which the major species present, in Lombardy polar pollen, are 57 kD and 7 kD (glyco)proteins. The binding of SP-A to pollen grains and their aqueous extracts was calcium ion dependent and was inhibited by mannose, and is therefore mediated by the lectin domain. Binding of SP-A to pollen grains was found to mediate adhesion of pollen grains to A549 cells. The results suggest that pollen grains or other carbohydrate-bearing particles (e.g. microorganisms) could potentially interact with different cell types via the collection receptor (C1q Receptor) in the presence of SP-A.

Calcium↗
PubMed1993

Increased expression of C1q receptors on neutrophils from inflammatory joint fluids.

C1q receptor (C1qR) expression was determined by immunofluorescence flow cytometry on neutrophils from paired peripheral blood and synovial fluid samples from 21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD). In both patient groups the levels of C1qR on circulating neutrophils were similar to that observed for normal control subjects, whereas on synovial fluid neutrophils significantly higher levels of receptor expression were observed. The mean percentage increases observed were: RA patients 47%, OAD patients 72%. C1q-bearing immune complexes were most prevalent in patients with RA, with the highest concentrations being found in synovial fluid samples. No correlation between immune complex levels and neutrophil C1qR expression was noted. Upregulation of C1qR expression is a feature of activated neutrophils from inflammatory joint fluids.

Antigen-Antibody Complex↗
PubMed1993

Universal precautions--a critical review.

The route of HIV transmission are now well defined. For health care workers the major occupational risk is from parenteral exposure to infected blood or other body fluids. To prevent such exposures, it would be prudent for HCWs to assume that all patients are potentially infected and a set of precautions applicable universally be followed in contacts with all patients. The provisions of "Universal Precautions" apply to blood, CSF, genital secretions and all body fluids. It is essential that barrier protection and washing of hands be practiced, body fluids be handled with care, correct sterilization and disinfection procedures be followed and a suitable system of waste disposal be evolved. Although the Universal Precautions have been useful in abating some of the more extreme behavior associated with treating AIDS patients and in establishing a rational approach to infection control, some of the recommendations have not been found to be efficacious or cost effective. Preventive measures recommend on the basis of demonstrated efficacy and aimed at routes of exposure that represent true risk are needed. The risks for occupational infection with blood borne pathogens have been a source of concern for health care workers (HCWs) because of their frequent and often substantial exposure to patient blood and body fluids. HCWs have long been identified as a group "at risk" for occupationally acquired Hepatitis B infection. With the development of acquired immunodeficiency syndrome (AIDS) epidemic, both HCWs and policy makers have become increasingly concerned about occupational risk from blood borne infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Gloves, Protective↗
PubMed1993

Collectin receptor (C1q receptor): structure and function.

Isolated collectin receptor (C1q receptor) is a single polypeptide chain of approximately 60 kDa (Malhotra and Sim, 1989). Sequence analysis shows that it belongs to a family of proteins which include calreticulin, a component of RoSSA autoantigen, Onchocerca volvulus antigen (RAL-1) and B50 murine melanoma antigen (Malhotra et. al., 1993). The receptor is widely distributed on leukocytes, platelets and endothelium and acts as a receptor for a group of structurally-related complement or lectin opsonins (the collectins), which include C1q, mannose binding protein (MBP), lung surfactant protein A (SP-A) and conglutinin (Malhotra et al., 1990).

Amino Acid Sequence↗
PubMed1993

Structure and homology of human C1q receptor (collectin receptor).

In this paper we report partial amino acid sequence for C1q receptor (C1qR). The N-terminal amino acid sequence of isolated C1qR and the sequences of peptides obtained by V8/trypsin digestion show a high degree of similarity to the cDNA-derived amino acid sequence of a human protein which was initially reported as a component of RoSSA and subsequently as calreticulin. This sequence in turn shows homology with Onchocerca volvulus antigen (RAL-1) and B50 murine melanoma antigen. A component of approximately 53,000 MW, isolated from human spleen, was found to have identical mobility on SDS-PAGE to C1qR and identical N-terminal sequence, but a different overall charge. Human antibodies from Sjögren's syndrome patients did not recognize C1qR, but showed positive reaction with the purified 53,000 MW component from spleen. Rabbit antibodies against denatured C1qR, in contrast, recognized both C1qR and the purified 53,000 MW component. The 53,000 MW spleen component thus has an identical N-terminal sequence to calreticulin, and to the reported RoSSA component, and is recognized by antibodies in Sjögren's syndrome sera. The data obtained indicate that C1qR and the reported calreticulin/RoSSA component are similar but not identical molecules, which belong to the same protein superfamily.

Agglutination↗
PubMed1992

Exendin-4, a new peptide from Heloderma suspectum venom, potentiates cholecystokinin-induced amylase release from rat pancreatic acini.

We examined the actions of exendin-4, a new peptide isolated from Heloderma suspectum venom, on dispersed acini from rat pancreas. Exendin-4 caused a 3-fold increase in cAMP but did not alter cellular calcium concentration. Exendin-4-induced increases in cAMP were inhibited by an exendin-receptor antagonist, exendin (9-39)NH2, but not by VIP-receptor antagonists. Whereas up to 1 microM exendin-4 alone did not alter amylase release, potentiation of enzyme release was observed when the peptide (greater than 30 pM) was combined with cholecystokinin. Potentiation of amylase release was also observed when exendin-4 was combined with carbamylcholine, bombesin or a calcium ionophore, A23187. These results indicate that stimulation of exendin receptors on rat pancreatic acini causes an increase in cellular cAMP. Although this increase in cAMP alone does not result in amylase release, combination of exendin-4 with agents that increase cell calcium results in potentiation of amylase release.

Amylases↗
PubMed1992

Ligational behavior of N-substituted acid hydrazides towards transition metals and potentiation of their microbiocidal activity.

New complexes of Cu(II), Ni(II), and Co(II) with 3-benzoyl-1-[2-N-(substituted-2'-thienyl methylmethylene/methylene)] prop-2-ene-1-oic acid hydrazides have been synthesized and characterized by elemental analysis, molecular weight determination, molar conductance, and magnetic moment and spectroscopic techniques. Conductance measurements indicate the nonionic nature of the complexes. From the spectroscopic studies, it has been concluded that the N-substituted acid hydrazides act as tridentate ligands forming an O-N-S conjugate system and coordinating with metal ions through oxygen of carbonyl group, nitrogen of azomethine, and sulphur of thiophene moiety. Octahedral geometry has been proposed for all the complexes. The ligands and their complexes were tested for in vitro growth inhibitory activity against phytopathogenic fungi viz. Alternaria alternata, Colletotrichum capsicum, Fusarium oxysporum, and Rhizoctonia solani at 28 degrees C; and bacteria viz. gram positive Bacillus subtilis and gram negative Escherichia coli at 37 degrees C by a two-fold serial dilution technique. In some cases an increase in the biocidal activity of the ligands as a consequence of coordination with metal ions was observed in terms of minimum inhibitory concentration (MIC) values. The trend of growth inhibition in the complexes was found to be in the order: Cu greater than Ni greater than Co.

Alternaria↗
PubMed1992

Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy.

The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication.

Aged↗
PubMed1992

Interaction of C1q receptor with lung surfactant protein A.

Earlier we reported the purification of C1q receptor (C1qR) from U937 cells and human tonsil lymphocytes (Malhotra, R. and Sim, R. B., Biochem. J. 1989. 218: 625) and showed that C1qR interacts with the ligands C1q, mannose-binding protein, conglutinin and lung surfactant protein A (SP-A) (Malhotra, R., Thiel, S., Reid, K. B. M. and Sim, R. B., J. Exp. Med. 1990. 172: 955). C1qR was characterized as an acidic glycoprotein, which, when solubilized, exists as a dimer of Mr 115,000 under non-denaturing conditions. In this article we provide evidence for binding of radioiodinated SP-A to U937 cells and show that binding of radioiodinated SP-A to U937 cells is specific, saturable, salt dependent and is inhibited by purified C1qR and by C1q. The interaction of SP-A with U937 cells was found to up-regulate the surface expression of C1qR. Incubation of SP-A with U937 cells at 37 degrees C for 80 min was found to increase the receptor number per cell. Increase in receptor number was inhibited in the presence of sodium azide and monensin. Incubation of cells with calcium ionophore A23187 induced increased surface expression in the absence of SP-A. The results indicate that interaction of SP-A with U937 cells triggers the expression of an intracellular pool of C1qR.

Amino Acid Sequence↗
PubMed1992

Synthesis, characterization, and microbiocidal activity of alpha-methyl-(2-thiophenomethylene) aryloxyacetic acid hydrazides and their metal complexes.

Complexes of alpha-methyl-(2-thiophenomethylene) aryloxyacetic acid hydrazides with Cu(II) and Zn(II) metal salts were synthesized and characterized by elemental analysis, molecular weight determination, molar conductance, and magnetic moment and spectroscopic techniques. In these complexes, the ligands form a conjugate O-N-S tridenate system, thus coordinating with metal through oxygen of the carbonyl group, nitrogen of azomethine, and sulphur of thiophenemoiety. Octahedral geometry is proposed for all the complexes. Antifungal activity of the ligands and their Cu(II) and Zn(II) complexes was determined against plant pathogenic fungi viz. Alternaria alternata, Rhizoctonia solani, Colletotrichum capsicum, and Glomeralla cingulata at 28 degrees C. Antibacterial activity of ligands and their metal complexes was determined on gram positive Bacillus subtilis and gram negative Escherichia coli bacteria at 37 degrees C by the serial dilution method. In some cases an increase in biocidal activity of the ligands on coordination with metal ions was observed in terms of minimum inhibitory concentration (MIC) values.

Anti-Bacterial Agents↗
PubMed1992

The effects of an LHRH agonist on testicular function in the cryptorchid rat.

To assess the effects of an LHRH analog (LHRH-ethylamide des gly10 D-Leu6) on the function of the cryptorchid testis, an animal model was created, using prepubertal male Sprague-Dawley rats (21 days old). The animals were divided into six groups: 1) sham operated; 2) sham + LHRH treated; 3) cryptorchid; 4) cryptorchid + LHRH treated; 5) cryptorchid and orchidopexed; 6) cryptorchid, LHRH treated and orchidopexed. Two weeks post cryptorchidism, the animals were treated with either saline or LHRH-analog (one microgram./rat/day) subcutaneously for a total of twenty five days. Orchidopexy was performed following hormonal treatment. The effects of treatment were assessed in terms of body and reproductive organ weights, serum testosterone and LH levels, sperm counts and motility and fertility. The results demonstrated that experimental cryptorchidism impaired reproductive function, which was restored by orchidopexy, alone. Treatment of cryptorchid rats (groups 4 and 6) with LHRH did not produce any lasting improvement in spermatogenesis or fertility.

Animals↗