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T Joseph

Publications and source records attributed to T Joseph.

143 records · Page 8Linked to original sources
PubMedDate not supplied

Synthesis and sequence-specific DNA binding of a topoisomerase inhibitory analog of Hoechst 33258 designed for altered base and sequence recognition.

The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. Intermolecular nuclear Overhauser effects (NOE) between the ligand and the DNA receptor fragment confirm that the ligand binds in the minor groove of the DNA, interacting with the centrally located 5'-GGCCA segment. In contrast to the steric clash between the benzimidazole rings of the parent Hoechst 33258 molecule and the guanine 2-NH2 groups, which renders it G.C avoiding and thus A.T base pair preferring, the ligand 1 described here overcomes these unfavorable interactions and instead exhibits a marked preference of G.C base pairs. This behavior appears to arise from additional stabilization due to H-bonding with the guanine 2-NH2 groups. Although a ligand-induced distortion at the binding site is qualitatively assessable, the overall B-type conformation of the DNA fragment is retained upon complexation. The structural conclusions drawn from the NOE-NMR evidence were confirmed by molecular mechanics and molecular modeling studies.

Base Sequence↗
PubMedDate not supplied

Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm.

PURPOSE: The purpose of this work was to determine the reproducibility of coronary total calcium score (TCS) with dual-slice helical CT and compare three acquisition protocols. METHOD: Fifty patients (59 +/- 10 years old) underwent dual-slice helical CT (collimation = 2 x 2.5 mm) and coronary angiography. Two successive scans were performed, resulting in three sets of images: pitch = 1, 360 degrees linear interpolation (LI) (A360); pitch = 1, 180 degrees LI (A180); and pitch = 1.5, 180 degrees LI (B180). TCS values, calculated using a volumetric method with a threshold of 90 HU, were compared, and the interscan variation was determined. Diagnostic performances were compared with receiver operating characteristic curves. RESULTS: Protocol A360 provided significantly lower TCS than protocols A180 and B180 (p < 0.0001). No statistical difference was seen between A180 and B180, which provided the lowest interscan variation (40 +/- 58%). However, no significant clinical impact of the observed interscan variations was found. CONCLUSION: Reproducibility of TCS with dual-slice helical CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not sufficiently reproducible to allow serial quantification of TCS over time.

Adult↗
PubMedDate not supplied

Effects of energy and protein restriction on acetylcholine sensitivity of rat isolated perfused heart.

Responses to acetylcholine of isolated perfused hearts obtained from rats which were acutely starved, chronically half-starved or protein-restricted were compared with those of paired control groups. Isolated hearts of totally starved rats showed no significant change in the responses elicited by 10 and 20 micrograms doses of acetylcholine as compared with paired controls. With 40 micrograms acetylcholine a significantly greater reduction (P less than 0.001) in heart rate and coronary flow was seen and the duration of the negative chronotropic action was significantly increased (P less than 0.05), as compared with controls. Isolated hearts of half-starved and protein-restricted rats responded to 10, 20 and 40 micrograms doses of acetylcholine with significantly greater reduction (P less than 0.001) in heart rate, coronary flow and increase in duration of negative chronotropic action (P less than 0.001) as compared to controls.

Acetylcholine↗
PubMedDate not supplied

Effect of diphenylhydantoin and lithium on whole brain serotonin, sodium and potassium in mice.

The effect of lithium and Diphenylhydantoin separately and in combination on whole brain serotonin, sodium and potassium were studied in mice. 9 day treatment with lithium was found to significantly raise brain serotonin. Lithium enhanced the sodium lowering effect of diphenylhydantoin. Though neither drug affected brain potassium, combination of the two drugs significantly lowered brain potassium. The possible mechanisms of these effects are discussed.

Animals↗
PubMedDate not supplied

Influence of dopaminergic receptor supersensitivity on anticonvulsant action of carbamazepine.

Dopamine (DA) receptor supersensitivity was induced in albino rats by haloperidol (5 mg/kg, ip day, for 18 days) and after 48 hr carbamazepine (CBZ) was administered in graded doses. The animals were subjected to Maximal Electroshock Seizures (MES) test, Minimal Electroconvulsive Threshold (MET) test and Pentylenetetrazole (PTZ)-induced convulsions test. Haloperidol pretreatment marginally increased the effect of CBZ against PTZ induced seizures, but not against electrically induced seizures (MES and MET tests).

Animals↗
PubMedDate not supplied

Influence of lithium on the anticonvulsant activity of carbamazepine.

The present study was undertaken to see whether the recently reported synergism between lithium and carbamazepine (CBZ) in mania also extends against convulsions. The anti-convulsant effect of various doses of CBZ was assessed in albino rats pretreated with vehicle or lithium salt (0.54 mEg/kg/day, p.o. for 9 days). The animals were subjected to 3 tests: maximum electro shock seizures (MES); minimum electro convulsive thresholds (MET) and pentylenetetrazol (PTZ)-induced convulsions: abolition of hind limb extension after electro shock, increases in the MET for appearance of neck jerk and absence of convulsions for one hr after PTZ were taken as parameters of the anticonvulsive effect respectively. In the MES and MET tests lithum did not alter the anticonvulsive effect of CBZ. Lithium, however, potentiated the anticonvulsant effect of CBZ against PTZ-induced convulsions.

Animals↗
PubMedDate not supplied

Acetylcholinesterase activity of rat brain and heart in starvation and protein restriction.

AChE activity was determined in the brain and heart of normal, acute totally starved, chronically semi-starved and chronically protein restricted groups of adult male rats. Neither acute total starvation nor chronic semi-starvation produced significant changes in AChE activity and protein content of the brain, while AChE activity and protein content in the heart were significantly decreased (P less than 0.01) after semi-starvation. Protein restriction, however, produced a significant decrease in AChE activity and protein content of both brain (P less than 0.01) and heart (P less than 0.001).

Acetylcholinesterase↗
PubMedDate not supplied

Acetylcholine levels of rat brain and heart in starvation and protein restriction.

Acetylcholine (ACh) levels and protein content in brain and heart were determined in normal, acutely starved, chronically semi-starved and chronically protein restricted groups of adult male rats. The only change observed in acute starvation and chronic semi-starvation was an increase in ACh level with a decrease in protein content in the heart, no change was observed in the brain. Protein restriction, however, produced a significant rise in ACh levels with a decrease in protein content of both brain and heart.

Acetylcholine↗
PubMedDate not supplied

Variations in brain and heart acetylcholine content in rat: cervical dislocation vs guillotine technique.

The stress induced in animals due to handling prior to sacrifice has been shown to produce changes in total acetylcholine (Ach) content of the brain and heart of adult rats. Two methods of killing the animals were compared viz. cervical dislocation and decapitation by a guillotine technique; the former method producing more handling stress than the latter. Ach levels were significantly lower both in brain and heart when the animals were killed by cervical dislocation.

Acetylcholine↗