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Biomedical subjects

K N Reddy

Publications and source records attributed to K N Reddy.

At least 37 records · Page 2Linked to original sources

Kallikrein-like activity of crotalase, a snake venom enzyme that clots fibrinogen.

During the amino acid sequence determination of crotalase (EC 3.4.21.30), the thrombin-like enzyme from the venom of Crotalus adamanteus (eastern diamondback rattlesnake), we found that, in addition to the expected structural homology with bovine thrombin (EC 3.4.21.5), there was even greater homology with porcine pancreatic kallikrein (EC 3.4.21.8). In exploring further the similarities between crotalase and kallikrein, several striking observations were made. First, crotalase was rapidly and specifically inhibited by the tripeptide affinity labeling derivative prolylphenylalanylarginine chloromethyl ketone, which is known to be a specific inhibitor of kallikrein. Second, NaDodSO4/acrylamide gel electrophoresis revealed that crotalase cleaves the plasma kallikrein-susceptible bonds in human high molecular weight kininogen, producing an intermediate with procoagulant activity. Crotalase-catalyzed cleavage of high molecular weight kininogen also liberates kinin as evidenced by rat blood pressure bioassay. Finally, crotalase exhibits substrate specificity not only for the thrombin chromogenic substrate S-2238 but also for the kallikrein substrates S-2302 and S-2266. Interestingly, one of the other reactions catalyzed by plasma kallikrein, the activation of plasminogen, was not one of the activities exhibited by crotalase.

Animals↗

Proactivator and activator levels of plasminogen in plasma as measured by caseinolysis.

A procedure is presented for the caseinolytic assay of plasminogen proactivator and activator levels in blood. The validity of the method was established and normal plasma proactivator levels were determined in 10 subjects. No detectible activator activity was found in these subjects. Venous occulsion produced a small rise in activator activity. Hageman-deficient and Fitzgerald trait plasmas did not produce activator activity after exposure to kaolin. The generation of activator activity in the Fitzgerald plasma was partly restored by the addition of purified high molecular weight kininogen, but the Hageman-deficient plasma was not corrected. The caseinolytic assay avoids some of the drawbacks which are inherent in methods which depend on fibrin dissolution for the detection of enhanced fibrinolytic states, provides a reproducible baseline, and may be sufficiently sensitive to detect changes of clinical interest.

Caseins↗

Kinetics of active center formation in dog plasminogin by streptokinase and activity of a modified streptokinase.

The rate of activation of dog plasminogen by excess streptokinase showed a significant delay as compared to the rate of activation with catalytic amounts of streptokinase. Studies of the reaction at high streptokinase levels with the active center reagent, p-nitrophenyl-p-guanidinobenzoate showed that only a fraction (13%) of the potential active centers were developed in a equimolar mixture of streptokinase and dog plasminogen in 15s and more than 10 min were required for the formation of 1 mol of active sites. In the first 15s, the yield of active sites could not be increased by increasing streptokinase 10-fold over the molar concentration of plasminogen, suggesting that active center development rather than complex formation was the rate-limiting step. The delayed reactivity seen in this system provides an interesting model for the study of conformationally induced active center formation. With catalytic amounts of streptokinase, the activation proceeded rapidly but reached a plateau, indicating the loss of activator activity in the reaction mixture. With successive additions of fresh streptokinase, complete activation was achieved. Polyacrylamide gel electorphoresis showed that a stable streptokinase-plasmin complex formed. However, in contrast to the human plasmin-steptokinase complex, a potent plasminogen activator in which streptokinase is found as a residue of 37,000 daltons, dog plasmin-streptokinase complex contained a residue of 25,700 daltons and the complex was inactive against canine and human plasminogen. The 25,700 fragment along, however, showed considerable activator activity when tested with human and dog plasminogens.

Animals↗

Ventricular septal defect with aortic regurgitation: a hemodynamic and angiographic profile in Indian subjects.

The records of 362 patients of Ventricular Septal Defect (VSD) were analysed to find out the incidence of aortic regurgitation (AR) and their hemodynamic and angiographic features. Thirty-seven patients (10.2%) were found to have AR, whose mean age was 13.4 years (range: 2-45) and male to female ratio was 5:1. Of the 37 cases 31 (84%) had infracristal and 6 (16%) had supracristal VSD. In 31 patients with infracristal VSD the prolapsing cusp was Right Coronary Cusp (RCC) in 14 (48%), Noncoronary Cusp (NCC) in 12 (41%) and both RCC and NCC in 3 (11%). Of the 6 patients with supracristal VSD the prolapsing cusp was RCC in 5 (83%) and NCC in 1 (17%). In two patients the AR was due to bicuspid aortic valve. The pulmonary artery pressure was normal in 26 of 37 (70.2%) patients and the left to right shunt was 1.5:1 or less in 23 of 37 (62%) patients. Nineteen of the 37 patients (51.3%) had grade I or II AR and the remaining 18 (48.7%) had grade III or IV AR. There was no relationship between the severity of AR and the location of the VSD. In conclusion, in this series, the incidence of VSD+AR is relatively higher and that of supracristal VSD is lower. In majority of patients the left to right shunt is small and pulmonary artery pressure within normal limits. The prolapse of RCC is more common in supracristal VSD and there is no relation between the severity of AR and the location of the VSD.

Adolescent↗

Correlation of 12 lead ECG QRS score with severity of aortic stenosis.

The hemodynamic data and electrocardiograms of thirty-three patients of moderate to severe aortic stenosis were analysed retrospectively to find out if there was any correlation between 12 lead ECG-QRS score and left ventricular peak systolic pressure (LVPSP) and/or peak systolic gradient (PSG) across the aortic valve. The mean age of the study population was 33.33 (+/- 15.02SD) years, with the male to female ratio being 9:2. The mean 12 lead ECG-QRS score in these 33 patients was 281 mm (+/- 46.02SD), the mean LVPSP 203.52 mmHg (+/- 46.62SD) and the mean PSG across the aortic valve was 81.0 mmHg (+/- 41.62SD). There was good correlation of 12 lead ECG-QRS score with LVPSP (r = 0.47, P less than 0.001) and with PSG across the aortic valve (r = 0.58, P less than 0.001), latter being more significant. The best correlation was however found between 12 lead ECG-QRS score and PSG across the aortic valve in patients over 35 years of age (r = 0.88). In conclusion there is a direct relationship between 12 lead ECG-QRS score and peak systolic gradient across the aortic valve and the latter can be approximately calculated non-invasively with the help of regression equation- Peak systolic gradient (in mmHg) = 12 lead ECG-QRS score/3 - 10.6

Adolescent↗

Results of 130 consecutive percutaneous transluminal coronary angioplasty (PTCA) procedures in single and multiple vessel coronary artery disease (CAD).

Over the last 1-year period, we performed 130 consecutive percutaneous transluminal coronary angioplasty (PTCA) procedures in 108 patients, 103 of them were males and 5 females. Their mean age was 50.9 +/- 6.83 years (range 33-70). All of them were symptomatic, manifested by acute infarction in 18 (17%), chronic stable angina in 30 (28%), unstable angina in 5 (5%) and post-myocardial infarction angina in 55 (51%) cases. Among these patients, single-vessel CAD was present in 42 (39%), double-vessel in 37 (34%) and triple-vessel CAD in 11 (10%) patients. Nine patients (8.3%) had total occlusion, and 18 (16.6%) had tandem or bifurcation lesions of target artery. Of the 112 PTCA procedures (excluding those in acute infarction), 53 (47%) were performed on LAD, 29 (26%) on RCA, and 30 (27%) on circumflex artery, with success rates of 86.7%, 83.3% and 82.7% respectively. The overall success rate was 85% (95 of 112). The PTCA was successful in 36 of 42 (85.7%), 32 of 37 (86.5%) and 9 on 11 (82%) patients with single, double and triple-vessel CAD respectively. The mean diameter stenosis reduced from 67.1 +/- 16.54% to 19.9% +/- 10.9%. PTCA was unsuccessful in 17 (15%) due to failure to cross the lesion in 11 (9.7%), failure to dilate in 1 (0.9%) and abrupt reclosure of dilated segment in 5 (4.4%). Four (3.5%) patients underwent CABG. Two patients had redo PTCA owing to restenosis at about 6 months of first PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗