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Biomedical subjects

S Krishnaswamy

Publications and source records attributed to S Krishnaswamy.

At least 91 records · Page 5Linked to original sources
PubMed1986

Use of monoclonal antibodies for the purification and characterization of the threonine-sensitive isozyme of maize homoserine dehydrogenase.

Monoclonal antibodies, highly specific for the threonine-sensitive isozyme of maize homoserine dehydrogenase, have been prepared and utilized to purify the enzyme to homogeneity. The results of one- and two-dimensional polyacrylamide gel electrophoresis under denaturing conditions indicate that the enzyme is composed of subunits of identical molecular weight. Apparent microheterogeneity of the subunits was observed during isoelectric focusing, but peptide maps generated by partial cleavage with three different chemical reagents did not reveal any differences among the proteins separated by isoelectric focusing. It is concluded that the subunits of the active dimeric and tetrameric configurations of the maize enzyme are identical or very similar. Evidence is presented which indicates that the enzyme purified by immunoaffinity chromatography retains all of the properties of freshly isolated enzyme, including the ability to undergo several ligand-induced slow transitions among four unique states and complex kinetic responses to physiological substrates. Two monoclonal antibodies are shown to interact differently with the purified enzyme. One, MC-11, reacts with all enzyme molecules, while the other, MC-3, is able to resolve two antigenically distinct subpopulations. These populations are present in approximately equal amounts in etiolated shoots and leaves of light-grown seedlings. However, the results of kinetic and hysteretic studies indicate that they are functionally indistinguishable. The antibodies appear to recognize a structural difference between the enzyme populations which does not result in detectable alterations in their catalytic or regulatory properties.

Alcohol Oxidoreductases↗
PubMed1983

Ligand-induced interconversions of maize homoserine dehydrogenase among different states.

The threonine-sensitive homoserine dehydrogenase has been isolated and extensively purified from shoots of Zea mays L. var. earliking. This enzyme is shown to be hysteretic under certain conditions. Progress curves of the NAD-dependent reaction catalyzed by the maize enzyme can be characterized by distinct lags prior to achievement of steady state velocities, reflecting transitions from less active species to a more active steady state form of the enzyme. Incubation of the enzyme for 1 min at 25 degrees C prior to initiation of the reaction profoundly influences the properties of the less active enzyme and the nature of the subsequent slow transitions during assay. When the feedback modifier, L-threonine, or KCl is included in the preincubation mixture, the transitions involve biomolecular association reactions. In the absence of either ligand, or in the presence of an appropriate mixture of both, a unimolecular transition occurs during assay. Three unique preincubation states of the enzyme have been identified on the basis of their response to substrates and effectors; whereas, the kinetic and regulatory properties of the steady state form of the enzyme are independent of preincubation conditions. Steady state can thus be achieved by three different transitions. Each transition is retarded by threonine and favored by substrates and potassium, although the effects of these compounds differ quantitatively. Under the conditions tested, monovalent cations have no effect on the steady state velocity of the enzyme. A model describing the relationships among the four unique states of the enzyme which is consistent with the present results and supported by previous observations is proposed.

Alcohol Oxidoreductases↗
PubMed1983

Characterization of ligand-induced states of maize homoserine dehydrogenase.

The threonine-sensitive homoserine dehydrogenase (L-homoserine: NAD(P)+ oxido-reductase), isolated from seedlings of Zea mays L., is characterized by variable kinetic and regulatory properties. Previous analysis of this enzyme suggested that it is capable of ligand-mediated interconversions among four kinetically distinct states (S. Krishnaswamy and J. K. Bryan (1983) Arch. Biochem. Biophys. 222, 449-463). These forms of the enzyme have been identified and found to differ in oligomeric configuration and conformation. In the presence of KCl and threonine a rapid equilibrium among three species of the enzyme (B, T, and K) is established. Each of these species can undergo a unique slow transition to a steady-state form under assay conditions. Results obtained from gel-filtration chromatography and sucrose density centrifugation indicate that the B and steady-state forms are tetramers and the T and K states are dimers. Evidence is presented to indicate that the rapid conversion from one dimeric species to the other can only occur via formation of the tetrameric B state. Chromatography under reacting-enzyme conditions provides direct support for the slow formation of a common steady-state species from any one of the other forms of the enzyme. The rate of transition is influenced by threonine, homoserine, NAD+, and, for transitions involving association reactions, by enzyme concentration. Small, reproducible differences in the apparent size of the T and K forms, and the B and steady-state species, are attributed to changes in conformation. This conclusion is supported by differential susceptibility of the enzymic states to proteolytic inactivation, by different rates of inactivation by dithio-bis-nitrobenzoate, and by alterations in their thermal stability. In addition, the B, T, and K states of the enzyme exhibit unique intrinsic fluorescence spectra. Spectral changes are shown to closely parallel changes in kinetic and hysteretic properties of the enzyme. The results of diverse methods of analysis are internally consistent, and provide considerable support for the conclusion that this pleiotropic regulatory enzyme can exist in any of several physically distinct states.

Alcohol Oxidoreductases↗
PubMed1983

Meso-atrial shunt in the surgical treatment of Budd-Chiari syndrome.

Three patients with idiopathic Budd-Chiari syndrome with occlusion of the hepatic veins and significant obstruction of the hepatic segment of the inferior vena cava are presented. The inferior vena caval obstruction precluded the use of conventional side-to-side portacaval or mesocaval shunts. Dramatic regression in liver size and resolution of ascites occurred in all three patients following the construction of meso-atrial shunts using wide-lumen woven Dacron grafts. Shunt patency was confirmed by angiography in two patients and Doppler studies in one. One patient died five months after surgery and another after 16 months. The shunts were widely patent at autopsy and the full length of the grafts were lined by neo-intima. The third patient is asymptomatic 20 months after surgery and is free of ascites. Our experience in these three cases suggests that patency can be expected in long synthetic grafts between the portal and systemic venous system provided the shunt is of adequate diameter and there is a pressure gradient between the two ends.

Adult↗
PubMed1983

Results of surgical treatment of ventricular septal defects with pulmonary hypertension.

Two hundred and twenty-five consecutive patients with interventricular septal defect and associated pulmonary hypertension have undergone corrective surgery at the Christian Medical College Hospital. The mean preoperative systolic pulmonary artery pressure was 70.5 (range 31-136) mm Hg and the calculated pulmonary vascular resistance ranged from 300 to 1680 dyn/s cm-5. A paracoronary right ventriculotomy was the approach of choice. Profound hypothermia and circulatory arrest were not used, even in 12 patients weighing under 10 kg. Among the older children and young adolescents there were 27 who had a calculated pulmonary vascular resistance of over 800 dyn/s cm-1 and their mortality was 22%, which is good when compared with that of other series. It is evident that both the early and the late death rate after surgery increase with the age of the patient, especially in those with associated pulmonary hypertension. In 69 patients studied after repair recatheterisation showed no residual defect by oximetry. The fall in the pulmonary artery pressures after surgery has been striking in most patients. The late death rate was 2.5%. The surviving patients are leading normal, active lives.

Adolescent↗
PubMed1983

Haemolytic effect of the scorpion Heterometrus fulvipes venom.

The haemolytic effect of the venom from scorpion Heterometrus fulvipes was studied using sheep erythrocytes. While there was no haemolytic effect seen directly by the erythrocytes, erythrocytes sensitized with homologous haemolysin were lysed by the venom. This factor in Heterometrus fulvipes venom having a 'complement like' haemolytic effect was found to be thermolabile and dialysable and sensitive to the action of 2-mercaptoethanol. It was identified as a low molecular weight peptide containing disulphide groups.

Animals↗
PubMed1983

Mitral valve replacement in the young patient with rheumatic heart disease. Early and late results in 118 subjects.

During a 14 year period, 118 young patients between 9 and 20 years of age underwent mitral valve replacement. In view of the acknowledged advantage of durability and minimal thrombogenicity, we chose the Starr-Edwards valve prosthesis in the large majority of our subjects. Other prostheses have also been used. Hospital mortality has been only 3% in the past 5 years. Frail, severely incapacitated children and adolescents have had an impressive spurt in growth and weight and have returned to normal activities. Nine of the patients have had a normal pregnancy and have borne children. The remarkable clinical improvement has been corroborated by hemodynamic benefit. Follow-up over a period 1 to 15 years (mean 5.09 +/- 3.3) showed a very low incidence of embolic phenomena. In Third World countries, rheumatic heart disease continues to be a daunting challenge with pronounced disability resulting in death. Mitral valve replacement in the young subject with significant rheumatic valve disease should not be delayed until severe pulmonary vascular changes and myocardial damage pose a major deterrent.

Adolescent↗
PubMed1981

Surgical treatment of congenital coronary artery fistula.

Six patients with congenital coronary artery fistula underwent successful corrective surgery. Precise diagnosis was established either by retrograde aortography or more recently by selective arteriography. The left coronary artery was involved in four and the right in two cases. The fistula communicated with the right ventricle in three and the right atrium in three subjects. The operative approach is dictated by the site of entry of the vessel into the cardiac chamber. The use of cardiopulmonary bypass for intracardiac repair allows accurate closure of the fistula thereby reducing the chances of recurrence. A follow-up of one to seven years showed that all patients are asymptomatic and leading normal lives.

Adolescent↗
PubMed1981

The adult ductus: review of surgical experience with 131 patients.

Results in patients over 14 years of age who have undergone surgical closure of a patent ductus arteriosus during the period 1967 through 1979 have been reviewed. There were 131 subjects (average age 22 years) with a slight male predominance, which is at variance with other reports. Sixty-two subjects underwent hemodynamic evaluation and of these, 30 had pulmonary artery pressures ranging from 50 to 150 mm Hg. Division and suture of the ductus with aortic cross-clamping under normothermic conditions was performed in 61 subjects. This approach was particularly indicated in cases in which the ductus was unusually short in relation to its diameter as well as in many with atheromatous changes at the aortic end. In 65 subjects, the conventional division and suture with ductus clamps was employed. Total cardiopulmonary bypass with transaortic patch closure of the ductus was carried out in three instances. There were five early deaths which were principally associated with severe pulmonary hypertension. During a follow-up period extending from 1 to 11 years, three subjects died, but the remainder are well and active. Recatheterization data in nine patients with severe pulmonary hypertension showed gratifying results.

Adolescent↗
PubMed1980

Experience with the surgical treatment of coarctation of the aorta in India.

Between 1961 and 1977, 51 patients underwent operations for coarctation of the aorta. The average age of presentation of these cases was higher than in other series. Only three were asymptomatic, a finding which is not seen in reports from the West. Operative procedures included resection and graft interposition, resection and end-to-end anastomosis, and bypass grafting. However, the technique of patch angioplasty, routinely performed in the last three years of this review, seemed by far the most satisfactory procedure. The overall operative mortality was 9.8%. Hypertension did not regress in some cases in spite of a successful operation. Recoarctation was not seen in this series. Associated defects influenced results adversely. The overall results of operation for coarctation of the aorta have been very satisfactory and comparable with those in other recorded series.

Abnormalities, Multiple↗
PubMed1980

Endomyocardial fibrosis from a surgical standpoint.

Successful surgical correction was accomplished in a 12-year-old boy with proved endomyocardial fibrosis. Pathological features and the role of surgical therapy in the management of this lesion are discussed. This report presents one of the youngest patients who has undergone endocardiectomy and valve replacement for right-sided endomyocardial fibrosis.

Child↗
PubMed1976

Massive left atrial thrombus complicating mitral stenosis with atrial fibrillation: results of surgical treatment.

Thirty-five patients with massive atrial thrombus complicating mitral stenosis and atrial fibrillation were treated surgically. The mean age in this series is lower than that reported in the West. Furthermore, the incidence of preoperative embolic manifestations has been less frequent in our experience. We believe it is desirable to document the presence of a thrombus by selective left atrial cineangiography. Surgical treatment was accomplished with an acceptable mortality. The vital role played by the use of low-molecular-weight dextran and early anticoagulation in decreasing the incidence of postoperative cerebral embolism is emphasized. Follow-up data in the survivors has shown excellent functional status with no late embolic phenomena in any subject.

Adult↗