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Biomedical subjects

S Narasimhan

Publications and source records attributed to S Narasimhan.

At least 19 recordsLinked to original sources

Anti-ulcer activity of crude alcoholic extract of Toona ciliata Roemer (heart wood).

The ethanol extract of Toona ciliata Roemer (heart wood) was evaluated for its anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer (antisecretory), HCl-ethanol induced ulcer (cytoprotective) and water immersion stress induced ulcer in rats. We found that Toona ciliata extract at a dose of 300mg/kg p.o. markedly decrease the incidence of ulcers in all the three models. Ethanol extract of Toona ciliata showed significant reduction in gastric volume, free acidity, total acidity and ulcer index. The plant extract also showed gastro protective activity (52.94%), whereas standard drug sucralfate showed 94.85%. Toona ciliata extract showed protection index 43.0% in water immersion stress induced ulcer, whereas standard drug omeprazole showed protection index 100%.

Animals↗

Analgesic activity of some Indian medicinal plants.

In the present study of some of the Indian medicinal plants Sida acuta whole plant (Malvaeae), Stylosanthes fruticosa (whole plant) (Papilionaceae), Toona ciliata (heart wood) (Meliaceao), Bougainvilla spectabilis (leaves) (Nyctaginaceae), Ficus glomerata (bark, leaves) (Moraceae) and Polyalthia longifolia (leaves) (Annonaceae). The different plants were used in folklore medicine in the treatment of toothache and strengthening of gums, anthelmintic, kidney diseases, analgesic, anti-inflammatory, hepatoprotective, antihyperglycaemic, antihyperglycaemic and anticancer. The extract was prepared using powdered material with ethanol, concentrated under vacuo and were evaluated for analgesic activity by analgesiometer at three dose level (100, 300 and 500mg/kg). Analgesic activity was significant with Toona ciliata (heart wood) ethanolic extract when compared with other extracts and its activity was confirmed by tail immersion method.

Analgesics↗

Monitoring the use of amiodarone: compliance with guidelines.

AIM: Careful monitoring of amiodarone is recommended because it produces a range of potentially severe adverse effects. The aim of this study was to compare existing practice at our hospitals with the current international guidelines for the use of this drug. METHODS: A retrospective audit was carried out on all patients aged 15 years or older, with a primary discharge diagnosis of tachyarrhythmia and who were commenced and discharged alive on amiodarone between 1 January 2000 and 30 June 2002 from Wellington and Kenepuru Hospitals, Capital and Coast District Health Board, Wellington, New Zealand. The medical records were examined for baseline measurements of renal, liver, thyroid and pulmonary function, the electrocardiogram and chest X-ray. Follow-up arrangements were sought postdischarge. A questionnaire was sent to the general practitioner requesting information on follow-up testing. RESULTS: During the trial period, 743 patients were admitted with a primary diagnosis of tachyarrhythmia. Eighty-six patients satisfied the entry criteria, and of these 58 were followed for at least 1 year postdischarge. Baseline testing of the electrocardiogram, full blood count and renal function testing was excellent (95-100%). Chest X-rays were carried out in 80% of patients. Baseline testing of thyroid (61%) and liver (44%) function was suboptimal. Two percent of patients had pulmonary function testing and no patient had a formal eye examination. At 6 months, only 32% had thyroid function tests and 41% had liver function tests. At 1 year, of those still on treatment, 35% had both liver and thyroid function tests. CONCLUSION: Monitoring of thyroid, liver and pulmonary function tests in patients on amiodarone is less than ideal. This is probably because of lack of awareness of current guidelines.

Aged↗

The isomeric compounds nimbolide and isonimbolide.

Nimbolide [systematic name: (4alpha,5alpha,6alpha,7alpha,15beta,17alpha)-7,15:21,23-diepoxy-6-hydroxy-4,8-dimethyl-1-oxo-18,24-dinor-11,12-secochola-2,13,20,22-tetraene-4,11-dicarboxylic acid gamma-lactone methyl ester], C27H30O7, was isolated from the leaves of Azadirachta indica, and its isomer, isonimbolide [systematic name: (4alpha,5alpha,6alpha,7alpha,15alpha)-7,15:21,23-diepoxy-6-hydroxy-4,8-dimethyl-1-oxo-18,24-dinor-11,12-secochola-2,16,20,22-tetraene-4,11-dicarboxylic acid gamma-lactone methyl ester], was prepared from a novel rearrangement reaction of nimbolide, using boron trifluoride etherate and tetrabutylammonium bromide. The reaction conditions are probably responsible for the ether cleavage, double-bond rearrangement and reformation of the ether linkage. As a result, there are conformational changes in two cyclopentane rings and the side-chain -CH2COOMe group. In isonimbolide, an R(4)(4)(24) hydrogen-bond motif is observed.

Azadirachta↗

Effect of auxins on berberine synthesis in cell suspension culture of Coscinium fenestratum (Gaertn.) Colebr--a critically endangered medicinal liana of Western Ghats.

Cell suspension culture of critically endangered Coscinium fenestratum was established from young leaf segments on WPM supplemented with auxins. Effect of 2,4-D, IAA, IBA and NAA was examined on cell growth and berberine production. Berberine was synthesized and released continuously into the liquid medium. Presence of 2,4-D stimulated cell growth, but was not inhibitory on berberine synthesis. On the contrary, NAA stimulated berberine biosynthesis, but was not favourable for cell growth. Among the auxins tested, highest yield of berberine (5.79 mg/30 ml; 4.14 times to that of control) was obtained with 4 mg/l of NAA, while the best cell growth (214.43 mg dry wt., 1.96 times to that of control) was observed in the presence of 2 mg/l of 2,4-D. IAA and IBA were not favourable for cell growth and berberine synthesis.

2,4-Dichlorophenoxyacetic Acid↗

A novel family of anticoagulants from the saliva of Ixodes scapularis.

Using biochemical and molecular approaches, we have identified a 9.8 kDa protein in the saliva of Ixodes scapularis that inhibits the intrinsic pathway of coagulation. The 9.8 kDa anticoagulant protein was purified by reverse-phase HPLC and its N-terminal amino acid sequence determined. The N-terminal sequence showed homology with Salp14, an immuno-dominant antigen present in the saliva of engorging I. scapularis nymphs. Recombinant Salp14 expressed in Escherichia coli prolonged the activated partial thromboplastin time (APTT) of human plasma in a dose-dependent manner and was a specific inhibitor of factor Xa. A cDNA encoding a 9.3 kDa protein, Salp9Pac, was subsequently isolated from an I. scapularis salivary gland cDNA library. Salp9Pac showed 93% identity to the N-terminal sequence of the anticoagulant purified by HPLC. These data indicate that the anticoagulant protein purified by HPLC, Salp9Pac and Salp14 are members of a family of novel coagulation protease inhibitors present in tick saliva. While recombinant Salp9Pac did not show biological activity in the assays tested currently, it is likely to be mechanistically different from its paralogues. This raises the possibility that ticks may enhance their adaptive ability to cope with a wide spectrum of proteases, by transcribing such structurally related anticoagulant proteins with different functions.

Amino Acid Sequence↗

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗

Chemical characterization of bovine urine with special reference to oestrus.

Cows' urine was analysed by gas chromatography mass spectrometry (GC-MS). The profiles from preovulatory, ovulatory and postovulatory samples were compared to establish any qualitative and quantitative differences that might have potential value in olfactory communication. Dichloromethane was used as the solvent for extraction of the compounds. Seven different compounds were detected, of which only two were common to all the chromatograms. The chemical profile of oestrous urine was distinguished by the presence of two specific compounds, viz. di-n-propyl phthalate and 1-iodoundecane, that were not found in the other samples. As oestrous urine has been shown to elicit sexual behaviour in cattle, these two characteristic peaks may represent important chemical compounds that elicit signals that allow the bull to detect 'oestrous odours'.

Alkanes↗

Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum.

Invading infective third-stage larvae (L3) of parasitic nematodes execute a series of programmed developmental events in response to a host-specific signal encountered during infection. One of these early events is the release of excretory/secretory products. Using an in vitro feeding assay that mimics these early events of infection, a protein released by in vitro activated larvae of the hookworm Ancylostoma caninum was identified. This protein, Ac-ASP-2, was partially sequenced, and the cDNA encoding it isolated by PCR and screening of an A. caninum L3 cDNA library. The Ac-asp-2 cDNA encodes a protein of 219 amino acids that is related to a previously identified protein, Ac-ASP-1, from hookworms. Both molecules are members of an evolutionarily diverse family of molecules that include the venom allergens of the Hymenoptera, and the testes specific proteins/sperm-coating glycoproteins of mammals. Homologues are present in nearly all nematodes tested, as demonstrated by PCR-hybridization and database searching. The Ac-asp-2 mRNA is synthesized in all life history stages, but the gene product is released only by L3 activated to feed in vitro. The wide distribution of the Ac-asp-2 in nematodes and its release in response to host specific signals suggests that Ac-ASP-2 serves an important function in nematode physiology and development, and possibly in the infective process of parasitic species.

Amino Acid Sequence↗

Evaluation of radioiodination of meta-iodobenzylguanidine (MIBG) catalysed by in situ generated Cu(I) and directly added Cu(II).

A reliable method of labelling MIBG with 131I is reported. Radioiodination involved nucleophilic exchange reaction (160 degrees C, 30 min) catalysed by directly added Cu(II) or by Cu(I) generated in situ by addition of Na2S2O5 to CuSO4. An additional step of purification of the radiolabelled MIBG by anion exchange chromatography is recommended. The radiochemical (RC) yield was over 90%, while the typical RC purity of 131I-MIBG was not less than 98%. Higher labelling yield was achieved with Cu(I) than when using Cu(II), and with 125I (commercial product) than with 131I obtained by wet radiochemical processing method in-house. The purity and stability of MIBG-131I was confirmed by biodistribution studies in monkeys with 0.03% and 0.8% uptake in adrenals and myocardium, respectively. It is concluded that Cu(I) or Cu(II) catalysed radioiodination method is well suited for production of MIBG-131I.

3-Iodobenzylguanidine↗

A resource of mapped human bacterial artificial chromosome clones.

To date, despite the increasing number of genomic tools, there is no repository of ordered human BAC clones that covers entire chromosomes. This project presents a resource of mapped large DNA fragments that span eight human chromosomes at approximately 1-Mb resolution. These DNA fragments are bacterial artificial chromosome (BAC) clones anchored to sequence tagged site (STS) markers. This clone collection, which currently contains 759 mapped clones, is useful in a wide range of applications from microarray-based gene mapping to identification of chromosomal mutations. In addition to the clones themselves, we describe a database, GenMapDB (http://genomics.med.upenn.edu/genmapdb), that contains information about each clone in our collection.

Chromosome Mapping↗

Experimental approaches to the development of a recombinant hookworm vaccine.

Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family have shown promise for reducing hookworm burdens after larval challenge infections in mice. Typically, these polypeptides are expressed in Escherichia coli and administered as an alum precipitate. Vaccine protection is antibody dependent. It is anticipated that a cocktail of different recombinant hookworm antigens may be required in order to effectively prevent heavy hookworm infections and disease. The progress of this work has been hampered by the absence of both a convenient laboratory animal with which to study hookworm infections resembling human infection, as well as the lack of easy availability of native hookworm antigens. In addition, useful human serologic correlates of antihookworm immunity are still poorly defined.

Ancylostoma↗

rexB of bacteriophage lambda is an anti-cell death gene.

In Escherichia coli, programmed cell death is mediated through "addiction modules" consisting of two genes; the product of one gene is long-lived and toxic, whereas the product of the other is short-lived and antagonizes the toxic effect. Here we show that the product of lambdarexB, one of the few genes expressed in the lysogenic state of bacteriophage lambda, prevents cell death directed by each of two addiction modules, phd-doc of plasmid prophage P1 and the rel mazEF of E. coli, which is induced by the signal molecule guanosine 3',5'-bispyrophosphate (ppGpp) and thus by amino acid starvation. lambdaRexB inhibits the degradation of the antitoxic labile components Phd and MazE of these systems, which are substrates of ClpP proteases. We present a model for this anti-cell death effect of lambdaRexB through its action on the ClpP proteolytic subunit. We also propose that the lambdarex operon has an additional function to the well known phenomenon of exclusion of other phages; it can prevent the death of lysogenized cells under conditions of nutrient starvation. Thus, the rex operon may be considered as the "survival operon" of phage lambda.

Adenosine Triphosphatases↗