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Biomedical subjects

C K Nair

Publications and source records attributed to C K Nair.

At least 19 recordsLinked to original sources
PubMed2001

Technetium-99m-cyclam AK 2123: a novel marker for tumor hypoxia.

Technetium-99m labeled cyclam N-2'-methoxyethyl-2-(3'-nitro-1'-triazole) acetamide (cyclam AK 2123) has been synthesized, radiolabeled and characterized as a hypoxic tumor imaging agent. Radiochemical purity was greater than 95%. Marker biodistribution was measured in normal Wistar strain rats at different time intervals after intra venous (i.v.) administration. In vivo distribution and scintigraphic imaging studies were performed after i.v. injection into mammary tumor-bearing rats using a gamma camera and associated computer. Intratumor partial oxygen pressure (pO2) and oxygen saturation measurements were performed to estimate the oxygenation status of the tumors. Tumor to muscle ratio (T/M) of 99mTc-cyclam AK 2123 was 8.5 which was compared with other tumor seeking radiopharmaceuticals, viz. 99mTc-(V) DMSA (3.07), 99mTc-citrate (5.29) and 201T1C1 (3.29). T/M ratios were also evaluated in comparison with radioiodinated iodoazomycin galactopyronoside (125I-IAZG). The ratio obtained was 18 for 99mTc-cyclam AK 2123 and 20 for 125I-IAZG, respectively. The increased concentration of radioactivity in these tumors suggests that this agent could be labelling hypoxic cells and have utility as an imaging agent.

Animals↗
PubMed2001

Effect of a hypoxic radiosensitizer, AK 2123 (Sanazole), on yeast Saccharomyces cerevisiae.

Sanazole/DNA repair/Hypoxic radiosensitization/DNA polymerases/Saccharomyces cerevisiae Yeast Saccharomyces cerevisiae can exist in two physiological states, namely anaerobic and aerobic. They differ in their response to gamma- radiation and radiomodification. We report hereon our results concerning radiosensitization by Sanazole (AK-2123), a well-known hypoxic radio sensitizer, whose mechanism of action has been studied extensively. The results have revealed that Sanazole (1 mM) when present during irradiation could specifically sensitize wild-type anaerobic yeast cells with a DMF of 2.4. In a radiation-sensitive mutant which lacks a DNA repair pathway specific for the recovery from gamma-radiation induced DNA damage, the extent of sensitization was considerably lower and the DMF was only 1.3. Studies on the liquid holding recovery of cells of both wild- type and rad52 yeast cells exposed to radiation in presence of Sanazole revealed that sensitization by Sanazole is due to a preferential increase in the DNA damage, and not by impairing DNA repair. This system thus holds promise for screening potential hypoxic chemical radiosensitizers.

Cell Hypoxia↗
PubMed2001

Diagnostic and prognostic value of Holter-detected ST-segment deviation in unselected patients with chest pain referred for coronary angiography: a long-term follow-up analysis.

OBJECTIVE: To evaluate the diagnostic and prognostic significance of ST-segment deviation detected by ambulatory Holter monitoring in unselected chest pain patients referred for coronary angiography. METHODS: Two hundred seventy-seven patients (71% were men) who underwent coronary angiography for evaluation of chest pain were studied with 24-h ambulatory Holter monitoring within 72 h of angiography. A lumen diameter reduction of > or = 50% was considered coronary artery disease. The ST-segment deviation was defined as > or = 1-mm deviation from the baseline lasting > or = 1 min separated by a minimum of 1 min. The patients were followed up for 65 +/- 21 months (mean +/- SD) for occurrences of death, myocardial infarction, hospitalization for unstable angina, and need for revascularization. RESULTS: Of the 277 patients, 223 (80%) had coronary artery disease. The prevalence of coronary artery disease was not significantly different in patients with (43 of 48 patients; 90%) and without (180 of 229 patients; 79%) Holter-detected ST-segment deviation. The diagnostic accuracy of Holter-detected ST-segment deviation in predicting the presence of coronary artery disease was poor (33%), with a sensitivity of 19% and a specificity of 91%. The presence of Holter-detected ST-segment deviation was not predictive of future cardiac events or death. CONCLUSION: The ST-segment changes detected on ambulatory Holter monitoring are of limited value in identifying coronary artery disease and predicting the future adverse cardiac events or death in unselected patients with chest pain.

Adult↗
PubMed2000

Redox reactions of sanazole (AK-2123) in aqueous solutions: a pulse radiolysis study.

The redox chemistry of sanazole, an efficient hypoxic cell radiosensitizer, generally referred to as AK-2123, was studied by pulse radiolysis with eaq-, CO2-., 2-propanol radicals and CH2OH radicals. AK-2123 reacts with eaq-, CO2-. and 2-propanol radicals at almost diffusion-controlled rates, producing a nitro radical anion (lambda max = 290 nm) within a few microseconds. The decay kinetics of the radical anion was independent of the pH. The radical anion reacts with oxygen with a rate constant of 3.4 x 10(6) dm3 mol-1 s-1. An electron-transfer reaction was observed from the thymine radical anion to AK-2123. From redox equilibria with methyl viologen, the one-electron reduction potential of AK-2123 in aqueous solution, determined by pulse radiolysis, was estimated to be -0.33 +/- 0.02 V vs. NHE. Depletion of intracellular nonprotein thiols did not mitigate the radiosensitizing affect of the hypoxic radiosensitizer, AK-2123.

Electron Transport↗
PubMed1996

Nuclear matrix bound DNA polymerase-beta in mouse fibrosarcoma: effect of gamma-radiation.

Nuclear matrices isolated from the mouse fibrosarcoma tumour cells contain the eukaryotic replicative enzyme DNA polymerase-alpha and the presumptive repair enzyme DNA polymerase-beta. Exposure of tumors to various doses of gamma-radiation (1.95 to 6.5 Gy) causes a 2-fold increase in the levels of only DNA polymerase-beta in the nuclear matrix. The increase in the levels of this enzyme is not discernible if the matrices are isolated 24 hr after irradiation. The rise in the levels of the repair enzyme DNA polymerase-beta could be indicative of radiation stress response of the tumour cells and their repair ability.

Animals↗
PubMed1992

Ten-year experience with mitral valve replacement in the elderly.

Limited data are available on mitral valve replacement in the elderly patient. Therefore we report our 10-year experience including predictors of perioperative mortality and subsequent long-term cardiac mortality in elderly patients with mitral valve replacement compared to younger patients. Of the 126 consecutive patients with mitral valve replacement, 26 were older (77 +/- 4, group 1) and 100 were younger (62 +/- 9, group 2) than 70 years. Bioprostheses were used more frequently in patients in group 1 (65% vs 7%, p less than 0.0001). Of the 21 clinical, ECG, hemodynamic, and angiographic variables studied, patients in group 1 had higher pulmonary artery systolic pressure (57 +/- 15 vs 48 +/- 19, p less than 0.05), fascicular block on ECGs (70% vs 33%, p less than 0.005), and greater pump time on cardiopulmonary bypass (160 +/- 75 vs 120 +/- 50 minutes, p less than 0.025). A trend toward a higher perioperative mortality rate was also seen in group 1 (27% vs 12%, p = 0.058). Predictors of perioperative mortality by multivariate analysis were the presence of aortic calcification and prolonged pump time on cardiopulmonary bypass in group 1 and coronary artery disease, female sex, elevated mean pulmonary artery pressure, and postoperative complete atrioventricular block in group 2. During a mean 4-year follow-up period, cardiac mortality and total mortality rates were 42% and 54%, respectively, for group 1 compared to 24% and 35%, respectively, for group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Chemical radiosensitization by misonidazole: production and repair of DNA single-strand breaks in Yoshida ascites tumor cells.

Formation of strand-breaks in DNA and its repair in Yoshida ascites tumor cells exposed to gamma radiation (100-400 Gy) in presence and absence of misonidazole (10 mM) were studied. The methodology involved pre-labelling of cellular DNA by 3H-thymidine during cell proliferation in rats, irradiation of cells in vitro and analysing sedimentation profile of DNA by ultracentrifugation in alkaline sucrose density gradients. Irradiation under euoxic conditions resulted in formation of about 1.5 times greater number of strand breaks as compared to those formed during irradiation under hypoxic conditions. Misonidazole (10 mM) by its presence along with the cells during irradiation under hypoxic conditions caused a 3-fold increase in the number of single strand breaks, but under euoxic conditions of irradiation the presence of misonidazole did not enhance the strand break formation. Incubation of cells irradiated in absence of misonidazole for 1 hr in tissue culture medium at 37 degrees C resulted in repair of substantial fraction of the strand breaks while there was no repair of the DNA strand breaks in cells irradiated in the presence of the chemical.

Animals↗
PubMed1990

Ten-year results with the St. Jude Medical prosthesis.

Although the hemodynamic characteristics and durability of the St. Jude valve prosthesis have been reported, the need for and the degree of anticoagulation in patients who receive these valves remain uncertain. Our 10-year experience with 165 patients (100 men and 65 women, mean age of 58 +/- 13 years), who underwent valve replacement with St. Jude prostheses, is reported. Of the 165 patients, 147 were treated with warfarin. A prothrombin time 1.3 to 1.8 times control (range 15 to 20 seconds) was maintained in 134 patients with single valve and 1.8 to 2 times control (range 20 to 25 seconds) in 13 patients with double valve prostheses. The 10-year actuarial event-free incidence from thromboembolic and hemorrhagic complications was 84 and 95%, respectively. Of the 8 patients receiving antiplatelet therapy alone, 4 had thromboembolic events. Of the 10 patients on neither warfarin nor antiplatelet therapy, 3 had thromboembolic events. The 10-year actuarial event-free incidence from valve failure was 95%. The 10-year actuarial patient survival was 55%. Thus, the St. Jude valve is a safe and reliable prosthesis with acceptable overall long-term performance in patients given a modest anticoagulation regimen. Patients who receive St. Jude prosthetic valves without anticoagulants have a high incidence of thromboembolic events despite therapy with antiplatelet agents.

Adolescent↗
PubMed1989

Long-term follow-up of patients with echocardiographically detected mitral anular calcium and comparison with age- and sex-matched control subjects.

One hundred seven patients with echocardiographically documented mitral anular calcium (MAC) and 107 age- and sex-matched control subjects without MAC were studied and followed for a mean of 4.4 +/- 2.4 (standard deviation) years. Fourteen (7%) patients were lost to follow-up. Compared with the control group, patients with MAC had higher frequency of precordial murmurs (p less than 0.0001), cardiomegaly (p less than 0.0001), left atrial enlargement (p less than 0.0001), and rhythm and conduction disturbances (p less than 0.0001). During the follow-up, patients with MAC had higher incidence of valve replacement (p less than 0.0025), permanent pacemaker implantation (p less than 0.0025), congestive heart failure (p less than 0.0001), thromboembolic cerebrovascular event (p less than 0.01), sudden death (p less than 0.001) and total cardiac death (p less than 0.0001). However, the frequencies of myocardial infarction, coronary artery bypass surgery and angioplasty, endocarditis or noncardiac death were not significantly different between patients with MAC and the control subjects. Thus, patients with MAC have higher frequencies of precordial murmurs, cardiomegaly, left atrial and ventricular enlargement, rhythm and conduction disturbances. They more frequently undergo valve replacement and permanent pacemaker implantation, develop congestive heart failure and die of cardiac causes than age- and sex-matched control subjects.

Adult↗
PubMed1989

Purification and characterisation of an inducible beta-galactosidase from Corynebacterium murisepticum.

The beta-galactosidase (EC 3.2.1.32) of Corynebacterium murisepticum (inducible by lactose and galactose) was purified by successive column chromatography on Sephadex G-200, DEAE-Sephadex A-50 and DEAE-cellulose (DE52). The enzyme was found to be a dimer of identical subunits of molecular mass 100,000 daltons. The Km values of the enzyme for the substrates lactose and o-nitrophenyl-beta-D-galactopyranoside (ONPG) are 16.7 mM and 4.4 mM, respectively, indicating, its low affinity for the substrates. The Ouchterlony immunodiffusion method exhibited immunological homogeneity of the enzyme preparation. The catalytic site of the enzyme does not take part in antigen-antibody reaction.

Chromatography↗
PubMed1989

Previously unreported adverse reaction to encainide.

We describe a patient with recurrent atrial fibrillation who suffered a previously unreported adverse reaction to encainide therapy manifested by fever, chills, diaphoresis and myalgia. The patient had a similar response upon rechallenging with encainide, which resolved on discontinuation of therapy.

Aged↗
PubMed1988

Clinical significance of exercise-induced bundle branch block.

To evaluate the diagnostic significance and long-term follow-up data of patients with exercise-induced bundle branch block (BBB), 10,176 consecutive patients' exercise test data were reviewed and 50 patients found to have exercise-induced BBB. Clinical, exercise test and arteriographic data were analyzed along with follow-up data during a mean of 43 months. Of the 50 patients, 37 had exercise-induced left BBB and 13 had exercise-induced right BBB. Significant coronary artery disease (CAD) was diagnosed in 26 of 37 patients (70%) with exercise-induced left BBB and in all 13 patients (100%) with exercise-induced right BBB. In patients who underwent coronary arteriography, data demonstrated a high prevalence of proximal left anterior descending disease (17 of 20, 85%). Follow-up data revealed that exercise-induced BBB was associated with a 36% (18 of 50) incidence of coronary events, including 16 patients who underwent coronary artery bypass grafting and 2 hospitalized for congestive heart failure. Results indicated that exercise-induced BBB was infrequent and occurred primarily in association with CAD, had a high prevalence of proximal left anterior CAD, infrequently had similar onset and offset heart rates, was reproducible and associated with a greater incidence of coronary artery bypass grafting than had been previously reported, although the incidence of cardiac events was similar to those investigations.

Adult↗
PubMed1988

Mitral annular calcification and coarctation of aorta.

Although coarctation of the aorta is associated with various cardiac abnormalities, its association with mitral annular calcification (MAC) is not reported. We therefore report a 37-year-old patient with postductal coarctation of the aorta and MAC. Considered to be a degenerative process, MAC is usually seen in elderly patients. It is uncommon in patients less than 50 years old and rare before the age of 40 years. Previous studies have reported increased frequency of cardiac conduction disturbances in patients with MAC compared to age- and sex-matched controls. This is in agreement with complete right bundle-branch block noted on the electrocardiogram of our patient. Clinicopathologic correlative studies and long-term follow-up may determine how such conduction disturbances develop and progress.

Adult↗