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R Srinivasan

Publications and source records attributed to R Srinivasan.

At least 181 records · Page 10Linked to original sources
PubMed1987

Far-ultraviolet laser ablation of the cornea: photoacoustic studies.

Wide bandwidth piezoelectric transducers made of thin (9 microns) polyvinylidene fluoride film have been used to make time-resolved measurements of the stress-wave generated by far-ultraviolet (193 nm) laser ablation in corneal tissue in vitro. At high fluence (approximately 250 mJ/cm2), ablation commences within 10 ns (+/- 5 ns) of the laser pulse and generates short acoustic impulses (approximately 30 ns). The time profile of the ablation, when coupled to the energy requirements for ablation from earlier work, allows the estimation of a temperature and a half-life for the thermal decomposition of the collagen in cornea. These values do not support a photothermal mechanism for the ablation under the experimental conditions.

Animals↗
PubMed1987

Afebrile pneumonitis in infants: predictors of outcome.

This study was performed to determine which elements of the history, physical examination, and laboratory data of infants with afebrile pneumonitis predict the need for hospitalization. We used a risk score based on clinical history and a respiratory score based on the respiratory physical examination, to assess 101 infants with afebrile pneumonitis in the emergency department. Admission and length of hospitalization were decided independently of the study. The population was divided into three groups depending on outcome: mild disease--outpatient management or hospitalization for up to 48 hours; moderate disease--three or more days of hospitalization; and severe disease--admission to the intensive care unit. Twenty-four infants were followed as outpatients. Seventy-seven children were hospitalized: 12 for 48 hours, and 61 for a mean of 4.5 days. Four children were admitted to the intensive care unit. Patients in group 2 versus group 1 were significantly younger and sicker on initial examination, as evidenced by a worse average respiratory score, general appearance, and severity of retractions. Other parameters, including risk score, did not predict course of illness as measured by length of hospitalization. Respiratory physical examination, especially general appearance and severity of retractions, and young age are associated with a worse outcome in afebrile pneumonitis.

Blood Gas Analysis↗
PubMed1986

Ablation of polymers and biological tissue by ultraviolet lasers.

When pulsed, ultraviolet laser radiation falls on the surface of an organic polymer or biological tissue, the material at the surface is spontaneously etched away to a depth of 0.1 to several micrometers. In the process, the depth of etching is controlled by the width of the pulse and the fluence of the laser, and there is no detectable thermal damage to the substrate. The material that is removed by etching consists of products ranging from atoms to small fragments of the polymer. They are ejected at supersonic velocities. This dry photoetching technique is useful in patterning polymer films. It is also under serious investigation in several areas in surgery.

Animals↗
PubMed1986

NADPH binding induced proton ionization as a cause of nonlinear heat capacity changes in glutamate dehydrogenase.

Functional group interactions involved in the formation of the glutamate dehydrogenase-NADPH binary complex have been studied by three independent but complementary approaches: the pH dependence of the overall dissociation constant measured by an improved differential spectroscopic technique; the pH dependence of the enthalpy of complex formation measured by flow calorimetry; and the pH dependence of the number of protons released to, or taken up from, the solvent in the complex formation reaction, measured by titration. We conclude that the coenzyme binds to the enzyme through three distinguishable interactions: a pH-independent process involving the binding of the reduced nicotinamide ring; a relatively weak "proton-stabilizing" process, occurring at low pH involving the shift at a pK of 6.3 in the free enzyme to 7.0 in the enzyme-NADPH complex; and a stronger "proton-destabilizing" process, occurring at a higher pH involving a shift of a pK of 8.5 in the enzyme down to 6.9 in the enzyme-NADPH complex. The proton ionization of the free enzyme involved in this third interaction exhibits some unusual thermodynamic parameters, having delta Go = +11.5 +/- 0.1 kcal mol-1, delta Ho = +19 +/- 1 kcal mol-1, and delta So = +23 eu. We show here that this proton ionization step is directly related to and indeed constitutes the "implicit" shift in enzyme macrostates which we have shown to be responsible for the existence of large highly nonlinear delta Cpo effects in the formation of this complex [Fisher, H. F., Colen, A. H., & Medary, R. T. (1981) Nature (London) 292, 271-272].

Animals↗
PubMed1986

Structural features facilitating the glutamate dehydrogenase catalyzed alpha-imino acid-alpha-amino acid interconversion.

Glutamate dehydrogenase catalyzes the reversible oxidation of L-proline and L-pipecolic acid to the corresponding cyclic alpha-imino acids. The active substrates are the amino acid anion in one direction and the iminium ion in the other. The oxidation of the ester, amide, and N-methyl derivatives of L-proline by enzyme-NADP+ and the reduction of N-methyl-delta 1-tetrahydropyridinium ion by enzyme-NADPH do not proceed to a detectable extent under the experimental conditions. The methyliminium ion, however, undergoes facile nonenzymatic reduction by NADPH. If it is assumed that the nonenzymatic reaction reflects the structural requirements of the redox step of the enzymatic reaction, then the lack of reactivity of the tetrahydropyridinium ion toward enzyme-NADPH must be due to the instability of the central complex. It appears that the alpha-carboxylate and NH groups in the amino acid anion and in the alpha-imino acid are involved in binding the substrates to the enzyme-coenzyme complexes. We conclude that each of these active substrates binds to its appropriate enzyme-coenzyme complex through a hydrogen bond between its NH group and a basic enzyme group; there is also an ionic bond in the central complex between the alpha-carboxylate group of the active substrate and a positively charged enzyme group. The five-membered amino acid anions are more reactive toward enzyme-NADP+ than the six-membered ones. The same reactivity order is seen for the reduction of imino acids by enzyme-NADPH. Since these effects are also present in the nonenzymatic reduction by NADPH we ascribe the ring size effects on V/Ksubstrate primarily to those on the hydride-transfer step.

Amino Acids↗
PubMed1986

An analysis of estimation of pulmonary blood flow by the single-breath method.

The single-breath method of determining pulmonary blood flow is a simple technique involving no inert gas or special maneuvers such as rebreathing or breath holding. The use of this elegant technique has been limited, however, largely because of questions regarding its accuracy. Previous analyses of the method have indicated that large errors in the estimated blood flow could result if data reduction is not handled carefully. In addition, an uncertain amount of error is introduced, if the CO2 retained by the lung tissue while measurements are being made is not taken into account in the calculations. This paper presents a rigorous approach for estimating the pulmonary blood flow by the single-breath method, which would minimize considerably the effects of measurement errors and would also allow for possible CO2 absorption by the lung tissue. It is based on the exact solution of the underlying equations that describe the dynamics of gas exchange in the lung. The analytic solution provides insight into the difficulties involved in extracting the desired information from the experimental data.

Humans↗
PubMed1985

Comparison of the energetics of the uncatalyzed and glutamate dehydrogenase catalyzed alpha-imino acid-alpha-amino acid interconversion.

The thermodynamic and activation parameters for the reduction of delta 1-pyrroline-2-carboxylic acid (an alpha-imino acid) by reduced nicotinamide adenine dinucleotide phosphate (NADPH) are compared with those for the reduction of the same imino acid by the glutamate dehydrogenase-NADPH complex. The enthalpies of activation and standard free energy changes for these two reactions are found to be virtually the same. The catalysis by the enzyme, expressed as the ratio of the reactivity of the enzyme--NADPH complex to that of NADPH itself in reducing the iminium ion, is entirely accounted for by a more favorable entropy of activation with enzyme--NADPH as the reductant. This entropic driving force is large enough to overcome the exergonic formation of the binary complex and still lead to considerable catalysis by glutamate dehydrogenase. Comparison of delta S not equal to and delta So values for the reduction of the iminium ion by NADPH suggests that the solvation of the transition state resembles that of the reactants, even though the substituent effects on rate have shown that the hydride transfer from the reduced coenzyme is complete at the transition state [Srinivasan, R., Medary, R. T., Fisher, H. F., Norris, D. J., & Stewart, R. (1982) J. Am. Chem. Soc. 104, 807]. The delta Go and delta S not equal to/delta So values for the reduction by the enzyme--NADPH complex indicate that this reaction has a fairly symmetric transition state, the solvation properties of which are intermediate between those of the reactants and those of the products.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Reversible reduction of an alpha-imino acid to an alpha-amino acid catalyzed by glutamate dehydrogenase: effect of ionizable functional groups.

The glutamate dehydrogenase catalyzed reduction of delta 1-pyrroline-2-carboxylic acid (PCA; an alpha-imino acid) with reduced nicotinamide adenine dinucleotide phosphate (NADPH) to give L-proline and NADP+ is employed as a model for the redox step of the corresponding enzyme-catalyzed reductive amination of alpha-ketoglutarate. We demonstrate the reversibility of the model reaction and measure its equilibrium constant. The pH profiles for the model reactions show that the active substrates are the N-protonated imino acid in one direction and the proline anion with a neutral amino group in the other. The V/K value for the imino acid reduction is enhanced by a group Z of pK = 8.6 in the enzyme-NADPH complex, while that for the proline reaction is unaffected by any such group in the enzyme-NADP+ complex. The following conclusions emerge from a comparison of the pH dependence of the rates for the model reactions with that for the oxidative deamination of L-glutamate [Rife, J. E., & Cleland, W. W. (1980) Biochemistry 19, 2328]. The N-protonated form of alpha-iminoglutarate and the conjugate base of glutamate are the active substrates. The redox step is not sensitive to the protonation state of the groups that catalyze the hydrolysis of bound alpha-iminoglutarate. The group Z, which facilitates the PCA reaction, plays no role in the binding of alpha-ketoglutarate. We propose a chemical mechanism for the glutamate reaction where an unprotonated enzyme group of pK = 5.2 in enzyme-NADPH catalyzes the conversion of the alpha-iminoglutarate to the carbinolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Azasterol inhibition of delta 24-sterol methyltransferase in Saccharomyces cerevisiae.

The inhibition of the delta 24-sterol methyltransferase (24-SMT) of Saccharomyces cerevisiae by side-chain azasterols is related to their nuclear skeleton and side chain nitrogen position. Inhibitory power [I50 (microM)] was found to be in the order of 25-azacholesterol hydrochloride salt (0.05) greater than 25-aza-24,25-dihydrozymosterol (0.08) greater than 25-azacholesterol approximately equal to 25-azacholestanol (0.14) greater than (20R)- and (20S)-22,25-diazacholesterol (0.18) greater than 24-azacholesterol (0.22) greater than 25-aza-24,25-dihydrolanosterol (1.14) greater than 23-azacholesterol (4.8). In the presence of azasterols, S. cerevisiae produces increased amounts of zymosterol, decreased amounts of ergosterol and ergostatetraenol, and the new metabolites cholesta-7,24-dienol, cholesta-5,7,24-trienol, and cholesta-5,7,22,24-tetraenol. Kinetic inhibition studies with partially purified 24-SMT and several azasterols suggest the azasterols act uncompetitively with respect to zymosterol and are competitive inhibitors with respect to S-adenosyl-L-methionine (SAM). These results are consistent with at least two kinetic mechanisms. One excludes competition of azasterol and zymosterol for the same site, whereas a second could involve a ping-pong mechanism in which 24-SMT is methylated by SAM and the methylated enzyme reacts with sterol substrate.

Aza Compounds↗
PubMed1984

Far-ultraviolet laser ablation of atherosclerotic lesions.

Far-ultraviolet (far-UV) (193 nm) laser radiation ablates arterial wall tissue, including noncalcified atherosclerotic lesions, with no apparent thermal damage to remaining tissue. This effect contrasts sharply with the thermal damage produced by visible-wavelength laser irradiation. The mechanism by which far-UV radiation interacts with tissue is predominantly photochemical rather than photothermal. Potential clinical applications include those in which geometrically precise removal of tissue, without thermal damage to the remaining substrate, is desired. Ultraviolet laser catheterization appears practical with respect to the availability of fiberoptic materials and high-pulse-rate excimer lasers.

Aorta↗