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Biomedical subjects

A K Taneja

Publications and source records attributed to A K Taneja.

10 recordsLinked to original sources
PubMed2006

Long term prognosis of heart failure after acute coronary syndromes without ST elevation.

BACKGROUND: Information about long term outcomes of patients with acute coronary syndromes (ACS) who have clinically diagnosed heart failure is scarce. METHODS: In a UK registry, this study evaluated patients with non-ST elevation ACS, recording treatment, and clinical outcomes for six months. In a subgroup, a four year mortality follow up was performed to estimate the impact of the clinical diagnosis of heart failure on survival. RESULTS: Of 1046 patients, 139 (13%) had a history of clinically diagnosed heart failure. At discharge, ACE inhibitors were prescribed for 58% and 28%, of those with and without a history of heart failure respectively (p<0.001). Rates of angiography, percutaneous intervention, and coronary artery bypass graft were 17.3% and 29.2% (p = 0.003), 5.0% and 8.4% (p = 0.17), and 5.0% and 7.5% (p = 0.3) for these groups respectively. Death or new myocardial infarction at six months occurred in 22% and 10% (p<0.001) and at four years death occurred in 60% and 20% of these groups respectively (p<0.001). In a multivariate analysis prior heart failure carried an odds ratio of 2.0 (p = 0.001) for death or myocardial infarction at six months and 2.4 (p<0.001) for death over four years. New heart failure was associated with an increased risk of death at six months (20% compared with 5%, p<0.001). CONCLUSION: A clinical history of heart failure carries a substantial risk of death in patients admitted with ACS without ST elevation. Nearly 60% of those with prior heart failure are dead after four years. After adjustment for confounding factors, prior heart failure more than doubles the risk compared with those with no history.

Aged↗
PubMed1988

Phosphorylation of alpha alpha- and beta beta-tropomyosin and synthetic peptide analogues.

A tropomyosin kinase partially purified from chicken embryos was used to study the phosphorylation mechanism of alpha alpha- and beta beta-tropomyosin and synthetic peptides containing the site of phosphorylation at Ser-283 and corresponding to residues 264-284 of the tropomyosin isoforms. The apparent Km is 47 microM for alpha alpha- and 265 microM for beta beta-tropomyosin, whereas the Vmax values are similar. The alpha [264-284] and beta [264-284] peptides have apparent Km values of 500 microM and 650 microM, respectively, and Vmax values similar to that of the intact tropomyosin. This indicates that the conformation of the phosphorylation site at the COOH-terminal end of tropomyosin contributes significantly to the phosphorylation of the substrate. Furthermore, the marginal difference in the Km values of the alpha- and beta-peptide cannot account for the 5-fold difference in the Km of the native alpha alpha and beta beta isoforms, suggesting that the conformations of alpha alpha- and beta beta-tropomyosin at the phosphorylation sites are significantly different. Phosphorylation of beta-peptide analogues, each with a single substitution corresponding to the alpha sequence, indicates that His-276 and Ile-284 have negative influences on the phosphorylation of the beta-peptide, whereas Met-281 improves it. Direct analyses of the time courses of phosphorylation of alpha alpha-tropomyosin at 37 degrees C, where head-to-tail polymerization is minimized, show that a single exponential can fit the data satisfactorily. This indicates a random phosphorylation of two identical chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Antigen-antibody interaction. The immunodominant region of EDP208 pili.

The EDP208 pilus contains a major antigenic determinant in the N-terminal dodecapeptide, as shown by E. A. Worobec, A. K. Taneja, R. S. Hodges, and W. Paranchych ((1983) J. Bacteriol. 153, 955-961). This peptide was chemically synthesized, coupled to bovine serum albumin with N-hydroxysuccinimidyl p-azido-benzoate, and used in immunoblot and enzyme-linked immunosorbent assays to show it was capable of reacting with anti-EDP208 pilus antibodies. Antibodies raised against the synthetic peptide conjugate were also capable of reacting with whole pili in these assays. To further examine the specific residues responsible for the antigenicity of this site, several peptide analogs were chemically synthesized. The relative affinity of these peptides for anti-EDP208 pilus antibodies was determined by a competitive enzyme-linked immunosorbent assay using the Fab fragment of anti-EDP208 pilus immunoglobulin G. From these results we established that the antigenic region of this peptide was the N-terminal pentapeptide, N-acetyl-Thr-Asp-Leu-Leu-Ala, and the key residues responsible for the antibody-antigen interaction are the N-acetyl-Thr1, Leu3, and Leu4. Hydrophobic interactions involving the methyl of the acetyl group and the leucine side chains make the largest contributions to the antigen-antibody interaction, while a lesser contribution is made by the Thr1 hydroxyl. The side chains of Asp2 and Ala5 contribute only weakly to the stabilization of the antigen-antibody complex.

Amino Acid Sequence↗
PubMed1984

Synthesis of a model protein of defined secondary and quaternary structure. Effect of chain length on the stabilization and formation of two-stranded alpha-helical coiled-coils.

Five polyheptapeptides (Ac-(Lys-Leu-Glu-Ala-Leu-Glu-Gly)n-Lys-amide, where n = 1-5) of 8, 15, 22, 29, and 36 residues were synthesized by the solid-phase method. The peptides were purified by reversed-phase high-performance liquid chromatography. The ability of these peptides to form two-stranded alpha-helical coiled-coils in benign medium (1.1 M KC1, 0.05 M PO4 buffer, pH 7.0) was monitored by molecular weight determinations and circular dichroism studies and their physical properties were compared to carboxamidomethylated alpha-tropomyosin at cysteine 190 (CM-tropomyosin). The peptides TM-8, TM-15, and TM-22 were shown to be monomeric in both denaturant (8 M urea) and benign medium by gel-filtration high-performance liquid chromatography on TSK G2000 SW while peptides TM-29 and TM-36 were shown to be dimeric in benign medium both by gel-filtration and sedimentation equilibrium experiments. The CD spectra of the polyheptapeptides TM-8, TM-15, and TM-22 show large increases in molar ellipticity at 220 nm on the addition of trifluoroethanol (helix-inducing solvent) to the benign buffer. By comparison, the two-stranded polyheptapeptides (TM-29 and TM-36) and CM-tropomyosin do not show any increase in molar ellipticity at 220 nm. The helicity of polyheptapeptides increases with increasing chain length, with TM-36 having a value comparable with CM-tropomyosin [( theta]220 = -31,800 degrees and -32,200 degrees, respectively) which is considered to be essentially 100% alpha-helical. These small two-stranded alpha-helical coiled-coils are considerably more stable to temperature and urea denaturation than CM-tropomyosin. Whereas CM-tropomyosin is almost completely denatured in the presence of 6 M urea, TM-29 and TM-36 maintain 22 and 70% of their helicity, respectively. The 30% denaturation values (t30) are 74, 62, and 37 degrees C for TM-36, TM-29, and CM-tropomyosin, respectively, in benign medium (1.1 M KC1:PO4 buffer, pH 7.0). The t30 values can be substantially decreased in the presence of denaturant (3 M urea, 0.1 M KC1, PO4 buffer, pH 7.0) to 62 and 43 degrees C for TM-36 and TM-29, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1983

Localization of the major antigenic determinant of EDP208 pili at the N-terminus of the pilus protein.

Trypsin digestion of pilin monomers from EDP208 conjugative pili causes cleavage of Lys12 to yield an N-terminal dodecapeptide, ET1 (Mr approximately equal to 1,500), and the remaining C-terminal fragment, ER (Mr approximately equal to 10,000). Using the amino acid sequence for ET1 provided by Frost et al. (J. Bacteriol. 153:950-954), we synthesized the N-terminal dodecapeptide chemically, conjugated it to bovine serum albumin, and subjected it to immunological studies. Antisera prepared against intact EDP208 pili as well as against the synthetic ET1-BSA conjugate were used in experiments involving an enzyme-linked immunosorbant assay and electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to nitrocellulose sheets. Both experimental approaches showed strong reactivity between the synthetic dodecapeptide and antiserum raised against whole pili. It was also found that antiserum raised against the synthetic peptide was reactive against intact pilus protein, indicating that the N-terminal dodecapeptide is an important antigenic determinant of the EDP208 pilus protein. Additional studies showed that the C-terminal fragment, ER, may contain one or two additional antigenic sites.

Antigens, Bacterial↗
PubMed1981

Pharmacological studies on 5-methoxymethyl-2'-deoxyuridine: a new antiviral agent.

Pharmacokinetic and pharmacodynamic properties of 5-methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity against herpes simplex virus, were investigated. After i.v. administration of [2-14C]MMUdR at 50 and 25 mg/kg to rats, the overall half life of the drug (T 1/2 Kel) was calculated to be 32 to 35 min. The biological half life of the drug (T 1/2 beta) was 89 min and the distribution half life (T1/2 alpha) was 6 min. The specific volume of distribution was calculated to be 1.28 to 1.35 liters/kg and the total body clearance rate of the drug was 10 ml/min/kg. The data were analyzed on the basis of a two-compartment open pharmacokinetic model. After i.p. administration of 50 mg/kg of [2-14C]MMUdR to mice, peak plasma levels of 35.6 micrograms/ml were attained in 10 min. The highest tissue concentrations of [2-14C]MMUdR in mice were 63 micrograms/g in kidneys (30 min) followed by 36 micrograms/g in liver and spleen and 30 to 32 micrograms/g in lungs and gut (20 min). MMUdR did not undergo biotransformation in plasma but urine was found to contain MMUdR (greater than 80%) and a small amount of radioactivity which comigrated with MMUdR monophosphate. Administration of 500 mg/kg of MMUdR i.v. to New Zealand White rabbits did not produce any observable effects on the heart rate, ECG pattern or respiration rate. Vasodilation of 39-sec duration was observed immediately after administration of MMUdR.

Animals↗
PubMed1980

N,N'-Dialkylbis(dichlorophenyl)ethylenediamines and -imidazolidines: relationship between structure and estradiol receptor affinity.

Diastereomeric N,N'-dialkylbis(dichlorophenyl)ethylenediamines and the corresponding imidazolidines with chlorine in the 2,4, 2,6, 3,4, and 3,5 positions were synthesized. Only the stereoisomers of the 2,6-dichloro-substituted compounds exhibit for N-CH3 (2e, 3e), N-C2H5 (2f, 3f), and N-C3H7 (2g, 3g) an affinity to the estradiol receptor (Ka values ranging from 9.1 X 10(4) to 9.1 X 10(6)), because the nitrogen atoms are shielded by the ortho-located chlorine atoms; therefore, a binding interaction with hydrophobic receptor areas is possible. These substances show weak uterotrophic activity and no significant effect on the growth of the DMBA-induced hormone-dependent mammary adenocarcinoma of the rat.

Animals↗
PubMed1980

Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2.

The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK-13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X-265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%.

Animals↗
PubMedDate not supplied

Protein design using model synthetic peptides.

We have designed and synthesized a small, unique protein molecule with defined secondary, tertiary and quaternary structure. This 35-residue peptide, containing a cysteine residue at its N-terminal end, was oxidized to form a 70-residue disulfide-linked two-stranded alpha-helical coiled-coil with the two alpha-helices parallel and in-register. The major contribution to the formation and stabilization of the alpha-helical coiled-coil is hydrophobic interactions between positions 2 and 5 of the heptapeptide repeat (Lys-Leu-Glu-Ala-Leu-Glu-Gly). The protein (L-protein) contains nine leucine-leucine hydrophobic interactions between the alpha-helices of the coiled-coil. Circular dichroism studies demonstrated that this protein in its reduced ([L (r)] or oxidized (L (o)] state was essentially 100% alpha-helical ([theta]220 = -34,050 and -32,000 degrees respectively) at pH 2 (0.1% aqueous trifluoroacetic acid). Our objective was to modify systematically the structure of L to delineate the contribution that various amino acid side chains make to the formation and stabilization of its three-dimensional structure. A-protein, which contains alanine instead of leucine at positions 16 and 19 of the hydrophobic repeat in each chain of the coiled-coil, was compared to the L-protein. At pH 2, the oxidized form of the A-protein [A (o)] was essentially 100% helical. However, the protein was much less stable to temperature denaturation compared to the L-protein. The replacement of two leucine-leucine interactions by two alanine-alanine interactions has a dramatic effect on the formation and stability of the two-stranded alpha-helical coiled-coil structure. The results of this study clearly demonstrate the validity of this synthetic model protein approach to understanding the molecular aspects responsible for the folding and stabilization of protein molecules.

Amino Acid Sequence↗