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Biomedical subjects

G Jayaraman

Publications and source records attributed to G Jayaraman.

At least 55 records · Page 3Linked to original sources

Estimation of increased flow resistance in a narrow catheterized artery--a theoretical model.

The changed flow pattern in a narrow catheterized artery is studied and an estimate of the increased flow resistance is made. The anomalous behaviour of blood in small blood vessels has been taken into account by modelling blood as a Casson fluid possessing some finite yield stress. Both the cases of steady and pulsatile flow situations are studied. The pulsatile flow is analysed by considering the pressure gradient as a periodic function of time with small inertial effects. The resulting quasi-steady non-linear coupled implicit system of differential equations governing the flow are solved using a perturbation analysis, where it is assumed that the Womersley frequently parameter is small (alpha < 1) which is reasonable for physiological situations in small blood vessels as well as in coronary arteries. The effect of pulsatility, catheter radius and yield stress of the fluid on the yield plane locations, velocity distribution, flow rate, shear stress and frictional resistance are investigated. Because of the yield stress theta, two yield surfaces are found to be located in the flow field. Depending on the ration kappa (catheter size/vessel size) ranging from 0.3 to 0.7 (which is widely used in coronary angioplasty procedures), the frictional resistance to flow in large blood vessels, where the effect of yield stress can be neglected (i.e. theta = 0), increases by a factory ranging from 3 to 33. In small blood vessels with the same range of catheter size and an unit pressure gradient, frictional resistance increase was by a factor of 7-21 when theta = 0.05 and 11-294 when theta = 0.1. For small values of kappa and theta, the frictional resistance increased to several hundred times thus implying that the combined effect of increased catheter radius and yield stress is to obstruct the fluid movement considerably.

Animals↗

Thermal denaturation of an all beta-sheet protein--identification of a stable partially structured intermediate at high temperature.

The thermal unfolding of an all beta-sheet protein, cardiotoxin analogue III, from the Taiwan Cobra (Naja naja atra) is studied at pH 2.0, 4.0 and 6.0. At pH 4.0, using circular dichroism and 1-anilino naphthalene-8-sulphonic acid (ANS) fluorescence binding studies, a stable partially structured intermediate is detected at 90 degrees C.

Anilino Naphthalenesulfonates↗

Induction of helical conformation in all beta-sheet proteins by trifluoroethanol.

The effect of 2,2,2-Trifluoroethanol (TFE) on the structure of five all beta-sheet proteins, isolated from the venom of the Taiwan cobra (Naja naja atra), is studied. In all the toxins used, it is observed that significant amount of alpha-helix is induced at higher concentrations of TFE. In all these proteins, the induction of helical conformation and disruption of the tertiary structure seem to occur simultaneously. The structural transitions induced by TFE in reduced and denatured protein appear to be different from those observed in the native protein(s). In our opinion, the findings reported herein could have significant implications on research in the area of protein folding.

Circular Dichroism↗

Internal packing conditions and fluctuations of amino acid residues in globular proteins.

In order to investigate the environmental conditions of amino acid residues in protein molecules, four kinds of packing studies (atomic, geometric, hydrophobic and hydration) were formulated and tested on two proteins; bovine pancreatic trypsin inhibitor (BPTI) and bovine pancreatic ribonuclease S (RNase S). The inter-relationship of these packings on the fluctuations of amino acid residues was analysed by comparing the packing results with the dynamical studies, such as the root-mean-square-deviation values of atomic displacements obtained from the trajectories of molecular dynamics simulation, temperature factor information from crystal structures and residue fluctuations in proteins from continuum model. These analyses yield information about the most fluctuating and most stabilizing residue sites. Comparison of the results obtained by these methods indicate a good agreement, specifying an inverse correlation between the residue packing and fluctuations. This kind of study is helpful in identifying the specific residue sites such as nucleation, receptor binding and antigenic determining sites which in a way indirectly correlates with the functional residues in protein molecules.

Amino Acids↗

Expression of aminopeptidase A, an angiotensinase, in glomerular mesangial cells.

Glomerular mesangial cells are known to express angiotensin II type 1 receptors and contract in response to circulating and/or locally produced angiotensin II. In addition, stimulation of mesangial cell matrix protein synthesis by elevated levels of angiotensin II is known to contribute to the development of glomerulosclerosis. Previously, we reported that mesangial cells were positively immunostained with antiserum directed against aminopeptidase A, the principal angiotensinase in the metabolism of angiotensin II. Here we demonstrate directly that aminopeptidase A is expressed in mesangial cells cultured from rat kidney. First, cultured mesangial cells had measurable aminopeptidase A enzymatic activity. Second, immunoblots for aminopeptidase A were positive for isolated glomeruli and mesangial cells, although two bands were seen for mesangial cells (approximately 138 and 144 kD), and only the larger band was seen for isolated glomeruli and kidney. Third, Northern blot hybridizations of total RNA from mesangial cells or kidney were positive and labeled similarly sized bands. Fourth, reverse transcription-polymerase chain reaction amplification of mesangial cell total RNA yielded a partial cDNA of the expected size that was confirmed by sequencing to be identical to rat kidney aminopeptidase A. These results indicate that aminopeptidase A is expressed within mesangial cells. These results further suggest that metabolism of angiotensin II by aminopeptidase A could play a protective role in minimizing the adverse effects of angiotensin II stimulation of mesangial cells.

Aminopeptidases↗

Effect of organic acids in the prevention of aggregation on rapid refolding of proteins.

The effect of organic acids on the aggregation of protein(s) during rapid refolding is studied. Using egg white lysozyme, it is observed that acetic acid not only prevents aggregation, but also aids the protein to refold back to its native, biologically active state. In contrast, formic acid, propionic acid and butyric acid fail to exhibit this property. Using circular dichroism spectroscopy it has been found that an 'aggregation-insensitive' partially folded intermediate state is induced in 0.35M acetic acid.

Acetic Acid↗

Identification of 'molten globule'-like state in all beta-sheet protein.

The cardiotoxin analogue III (CTX III), isolated from the Taiwan Cobra venom (Naja naja atra), is a sixty amino acid, all beta-sheet protein. The 2,2,2-trifluoro ethanol (TFE) induced unfolding of CTX III is studied under acidic conditions (pH 2.5). Using circular dichroism, 1-anilino-8-napthalene sulphonic acid binding and NMR experiments, it is shown that stable, partially structured state(s) ['molten globule'-like state] is formed between 50 and 80% TFE concentrations. The protein was found to exist in an unfolded state in 80% TFE containing 2M urea. The TFE induced unfolding process is shown to be completely reversible. In the 'molten globule' state of CTX III in 80% TFE, though portion(s) of the backbone of the protein assume helical conformation, most of the original beta-sheet secondary structural elements in the protein are intact. In our opinion, this is the first report of the identification of a 'molten globule'-like state in the unfolding pathway of an all beta-sheet monomeric protein.

Anilino Naphthalenesulfonates↗

Conformational studies of a synthetic cyclic decapeptide fragment of rat transforming growth factor-alpha.

The solution conformation of a synthetic cyclic decapeptide [with sequence mimicking the third disulfide loop of rat transforming growth factor-alpha (rTGF-alpha)] in deuterated dimethyl sulfoxide was studied by 2D NMR. The determination of solution structures was based on NOE interproton distances, using a combination of distance geometry and simulated annealing protocols. The convergence of the selected structures was evident from the small atomic pairwise root-mean-square deviation values among them. Good agreement was noted between the experimental and simulated NOESY spectra, thereby reflecting the accuracy of the calculated solution structures. Analysis of the structures indicates that the residues Tyr5 and Arg9 exhibit similar side chain orientation as that in the corresponding disulfide loop of human transforming growth factor-alpha.

Amino Acid Sequence↗

Three-dimensional structure in solution of griseoviridin, a group A antibiotic.

The solution conformation of griseoviridin, a broad spectrum antibiotic, has been determined by 1H-NMR in deuterated dimethylsulfoxide. The structural determination is based on experimental data of NOE constraints Five structures were obtained from restrained molecular dynamics calculations, by imposing (the condition for) a minimum violation of distance constraints. These structures satisfy well the experimental restraints, with small values of NOE violation and total energies. On comparison with its crystal structure, a good agreement is noted with a backbone root-mean-square deviation value of 0.084 nm. However, a small variation between the structures is observed at the aminodecanoic acid part of the molecule.

Anti-Bacterial Agents↗

Cardiotoxin II from Taiwan cobra venom, Naja naja atra. Structure in solution and comparison among homologous cardiotoxins.

The three-dimensional structure in solution of cardiotoxin II, a membrane toxin from the venom of Taiwan cobra, Naja naja atra, was determined using 1H nuclear magnetic resonance spectroscopy and molecular modeling based on the hybrid distance geometry/dynamic simulated annealing technique. A complete sequence-specific proton assignment was obtained, and the secondary structures of the protein were determined from information on nuclear Overhauser effect connectivities, coupling constants, and hydrogen exchange were confirmed using the main-chain-directed strategy. Twelve simulated annealing structures found to be within a single family were selected based on the condition of distance constraint violation less than 0.02 nm and the dihedral angle violation less than 4 degrees. The average atomic root mean square deviation between the selected structures and their geometric average are 0.079 nm for the backbone atoms and 0.137 nm for all heavy atoms; they are 0.044 nm and 0.117 nm, respectively, when considering the secondary structural residues only. The molecule adopts a compact structure consisting of three major loops emerging from a globular head. These loops contain five strands to form double- and a triple-stranded antiparallel beta sheets. Comparisons are made between this structure and those of its homologous cardiotoxins in order to derive further information on their structural variations.

Amino Acid Sequence↗

The strength and stiffness of thoracic implant anchors in osteoporotic spines.

OBJECTIVE: To gain a better understanding of factors affecting dorsal implant pull-out strength and stiffness so thoracic spinal implant fixation can be improved. METHODS: Posterior pull-out testing of six thoracic implant anchor types was performed on 54 osteoporotic human vertebra, T2-10, with an average bone mineral density of 0.67 g/cm2. RESULTS: The mean loads at neural arch failure were similar (296 to 382 N). Pedicle strength was greatest at T2 and least at T3. Hook claws were stiffer than sublaminar wires (121 N/mm and 180 N/mm versus 42 N/mm and 52 N/mm, respectively). Facet hook and pedicle hook claws were comparable, as were subpars wires. Bone mineral density of the vertebral bodies correlated with the stiffness of the sublaminar wire anchors only. CONCLUSION: To optimize the strength and stiffness of implant constructs designed to resist forward flexion, this study supports using hook-claws rather than sublaminar wires and extension of fixation to T2 when clinically realistic.

Aged↗

A computerized technique for analyzing lateral bending behavior of subjects with normal and impaired lumbar spine. A pilot study.

STUDY DESIGN: A computerized technique, employing a motion analysis system and a force platform, was developed to analyze lateral bending behavior of subjects with normal and painful spines. METHODS: Lateral bending was quantified using motion (angle and speed of rotation), force (ground reaction kinetics), and biomechanical behavior ("compliance" and "transfer mobility") characteristics of four discrete spinal segments measured during standing, range of bending, and bending at normal and maximum speeds. RESULTS: For subjects with pain, there were reductions in the range of lateral bend (43%) and speed of rotation (39%). Ground reaction moment about the medial-lateral axis was greater (58%), whereas that about the anterior-posterior axis was less (28%). "Compliance" was less (25%), whereas "transfer mobility" was greater (24%). CONCLUSIONS: The findings suggest that the characteristics of lateral bending, rather than range of motion, is most affected in subjects with pain.

Adult↗

Effects of pretwist on biomechanical properties of canine patellar tendon.

The purpose of this study was to measure the effect produced on canine patellar tendon of a 90 degree pretwist on the following mechanical properties: failure stress, failure strain, average elastic modulus, and strain energy density. Forty adult mongrel dog cadavers, killed for other studies, were used. Paired patellar tendons were isolated with patellar and tibial bone and the central 4.0-4.6 mm of tendon used for testing. Specimens were elongated to failure using a Materials Testing System (MTS). Only those paired specimens both failing in substance were analyzed. Eight paired specimens were analyzed, both with 0 degree twist, for right-left reproducibility. Thirty-two paired specimens were randomly assigned to four groups: right 0 degree/left 90 degree clockwise pretwist; right 0 degree/left 90 degree counterclockwise; left 0 degree/right 90 degree clockwise; left 0 degree/right 90 degree counterclockwise. No statistically significant differences were present between the paired untwisted specimens in any mechanical property. In the pretwisted specimens, there were statistically significant differences between the group left/clockwise and right/counterclockwise and the group left/counterclockwise and right/clockwise with respect to the mechanical properties failure stress, average elastic modulus, and strain energy density. No statistically significant differences were observed between the two groups for failure strain. For the canine patella-patellar tendon-tibia complex (PPTTC), the mechanical properties failure stress, average elastic modulus, and strain energy density are sensitive to both side (left/right) of PPTTC and direction (clockwise/counterclockwise) of pretwist. Pretwist of patellar tendon grafts in anterior cruciate ligament reconstruction may produce significant changes in their mechanical properties that vary with the direction of twist.

Animals↗

Sodium ion transport in the intestinal wall: a mathematical model.

A theoretical approach to study the uptake of sodium ions across the gastrointestinal mucosa and the concentrations at which they are taken up into the underlying blood capillaries has been attempted. A two-phase model of the mucosa is considered, consisting of an extracellular phase and a cellular phase. The model takes into account two important modes of transport: diffusion under concentration gradient and potential gradient (electrodiffusion) and active transport which is ATPase enzyme mediated. Appropriate partial differential equations for the two mechanisms of transport are derived and are solved by iterative methods. An approximate distance from the lumen where the capillaries lie is somewhere between 10 and 15% of the total wall length. The mean concentration of sodium ions made available for absorption at the capillaries is studied with time. A functional form for the variation of potential with respect to distance is proposed, and by comparing model solutions with experimental data it is calculated explicitly.

Animals↗

Joint reaction forces during femoral lengthening.

The purpose of this study was to observe the reactive force across the hip and knee joint in a cadaver study during simulated femoral lengthening. Load cells were placed in the hip and knee joints while force measurements were taken after every 1 mm of lengthening. The lengthening was performed on one side with a distal osteotomy and on the other with a proximal osteotomy to determine if the level of the osteotomy had any affect on the forces across the proximal and distal joints. The study showed that the forces at the hip and knee joints increased during lengthening. The proximal osteotomy appeared to increase the amount of force at the hip joint. The force at the knee joint was less affected by the level of the osteotomy. The relative force between the knee and the hip was approximately a 2:1 ratio with a distal corticotomy as opposed to a 1:1 ratio with a proximal osteotomy. From this study, it is suggested that if instability of the hip is a concern during femoral lengthening, then a distal osteotomy should be used.

Adult↗

The effect of a stiff spinal implant and its loosening on bone mineral content in canines.

A canine spine surgery model was used to study bone mineral loss induced in vertebrae bypassed by stiff implants. Loosening of implants was measured, and a determination was made as to the effect of loosening on the degree of bone mineral loss. Sixteen dogs were implanted with a rigid screw-rod construct and randomized to one of four groups depending on the motion segments immobilized. No fusions were performed. Bone mineral was studied by DEXA at baseline, and postoperatively at 3, 6, and 9 months. Loosening measurements were made at the implant-implant interface and the implant-bone interface at 9 months postoperatively. Results show that bone mineral loss occurred uniformly at 3 months postoperatively in vertebrae spanned by the implants, with the average bone mineral density at 3 months representing 81% of baseline. When the implant remained secure, bone mineral loss persisted at 6 and 9 months but did not worsen. When the implants loosened, there was recovery of bone mineral to the baseline level by 9 months postoperative.

Absorptiometry, Photon↗

Preparative chromatography in biotechnology.

The field of preparative chromatography has experienced several important advances recently in both the structure of chromatographic materials and modes of chromatographic operation. This review presents recent applications of preparative chromatography in biotechnology, as well as novel stationary phase materials and engineering approaches to preparative chromatographic bioseparations.

Animals↗