G.N. Ramachandran (1922-2001).
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Biophysics↗
Biomedical subjects
R Sarma
Publications and source records attributed to R Sarma.
PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia.
Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.
Adult↗
Crystal structure of the rat liver fructose-2,6-bisphosphatase based on selenomethionine multiwavelength anomalous dispersion phases.
The crystal structure of the recombinant fructose-2,6-bisphosphatase domain, which covers the residues between 251 and 440 of the rat liver bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, was determined by multiwavelength anomalous dispersion phasing and refined at 2.5 A resolution. The selenomethionine-substituted protein was induced in the methionine auxotroph, Escherichia coli DL41DE3, purified, and crystallized in a manner similar to that of the native protein. Phase information was calculated using the multiwavelength anomalous dispersion data collected at the X-ray wavelengths near the absorption edge of the K-shell alpha electrons of selenium. The fructose-2,6-bisphosphatase domain has a core alpha/beta structure which consists of six stacked beta-strands, four parallel and two antiparallel. The core beta-sheet is surrounded by nine alpha-helices. The catalytic site, as defined by a bound phosphate ion, is positioned near the C-terminal end of the beta-sheet and close to the N-terminal end of an alpha-helix. The active site pocket is funnel-shaped. The narrow opening of the funnel is wide enough for a water molecule to pass. The key catalytic residues, including His7, His141, and Glu76, are near each other at the active site and probably function as general acids and/or bases during a catalytic cycle. The inorganic phosphate molecule is bound to an anion trap formed by Arg6, His7, Arg56, and His141. The core structure of the Fru-2,6-P2ase is similar to that of the yeast phosphoglycerate mutase and the rat prostatic acid phosphatase. However, the structure of one of the loops near the active site is completely different from the other family members, perhaps reflecting functional differences and the nanomolar range affinity of Fru-2,6-P2ase for its substrate. The imidazole rings of the two key catalytic residues, His7 and His141, are not parallel as in the yeast phosphoglycerate mutase. The crystal structure is used to interpret the existing chemical data already available for the bisphosphatase domain. In addition, the crystal structure is compared with two other proteins that belong to the histidine phosphatase family.
Acid Phosphatase↗
Preliminary X-ray analysis of a truncated form of recombinant fructose-2,6-bisphosphatase.
The bisphosphatase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and a C-terminal 30 amino acid truncated form were expressed in high yield in Escherichia coli and purified to homogeneity. The separately expressed bisphosphatase domain and its C-terminal truncated form had kinetic properties similar to the bisphosphatase of the intact bifunctional enzyme, but their turnover numbers were fourfold higher. The truncated enzyme crystallized in space group P1 with two molecules per asymmetric unit. The determined cell dimensions are: a = 41.9 A, b = 43.5 A, c = 57.6 A, alpha = 95.2 degrees, beta = 99.3 degrees, and gamma = 106.2 degrees. These crystals diffract to 2.0 A resolution when exposed to synchrotron radiation and are suitable for crystallographic structure analysis.
Animals↗
Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro.
Gerstmann-Sträussler-Scheinker disease (GSS) is a prion-related encephalopathy pathologically characterized by massive deposition of prion protein (PrP) amyloid in the central nervous system. The major component of amyloid fibrils isolated from patients of the Indiana kindred of GSS (GSS-Ik) is an 11-kDa fragment of PrP spanning residues 58 to approximately 150. These patients carry a missense mutation of the PRNP gene, causing a Phe-->Ser substitution at codon 198. We investigated fibrillogenesis in vitro by using synthetic peptides homologous to consecutive segments of GSS-Ik amyloid protein (residues 57-64, 89-106, 106-126, and 127-147) as well as peptides from the PrP region with the GSS-Ik mutation (residues 191-205 and 181-205, both wild type and mutant). Peptide PrP-(106-126) formed straight fibrils similar to those extracted from GSS brains, whereas peptide PrP-(127-147) formed twisted fibrils resembling scrapie-associated fibrils isolated from subjects with transmissible spongiform encephalopathies. Congo red staining and x-ray fibril diffraction showed that both straight and twisted fibrils had tinctorial and conformational properties of native amyloid. Conversely, the other peptides did not form amyloid-like fibrils under similar conditions. These findings suggest that the sequence spanning residues 106-147 of PrP is central to amyloid fibril formation in GSS and related encephalopathies.
Amino Acid Sequence↗
Encephalopathy, myelopathy, optic neuropathy, and anosmia associated with intravenous cytosine arabinoside.
Coma, hemiparesis, unilateral optic neuropathy, and anosmia manifested in a patient with leukemia after he received only three courses of intravenous high-dose cytosine arabinoside (ARA-C). The patient's mental status returned to normal after several days, and his hemiparesis resolved. However, the visual loss persisted, and near complete visual loss in the other eye ensued over the following month. Severe bilateral optic atrophy appeared as the visual loss progressed. Anosmia became evident after resolution of the coma and did not improve. The patient had previously had a thoracic myelopathy 2 weeks after receiving low-dose i.v. ARA-C. The neurotoxicity of high-dose i.v. ARA-C may arise at much lower cumulative doses than has been reported. In addition to cerebellar dysfunction and somnolence, high-dose i.v. ARA-C may produce optic neuropathy, anosmia, and hemiparesis.
Adult↗
Induced abortion among the Pati Rabha women of Boko area, Kamrup district, Assam.
"Acceptance of induced abortion as a device of family planning among the Pati Rabha of Boko area [India] was studied. Out of 345 couples, practising various family planning devices, 86 (24.93%) accepted induced abortion. Of the total 629 conceptions of these 86 women, 137 (21.78%) conceptions were terminated by induced abortion.... The highest percentage (18.24%) of the induced abortion was done at the 6th order of pregnancy, 62.79% of the women accepted the induced abortion only once in their reproductive period. Most (91.86%) of the acceptors were illiterate and all of them were house wives." Consideration is given to the use of traditional methods of inducing abortions.
Abortion, Induced↗
Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.
BACKGROUND: The pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved. METHODS AND RESULTS: Hemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2, 60 +/- 2 mm Hg). There was a significant increase in total body water (+21%), extracellular volume (+45%), plasma volume (+45%), blood volume (+88%), and exchangeable sodium (+38.2%). Renal plasma flow was severely reduced (-63.2%), but glomerular filtration rate was only mildly decreased (-32%). Significant increases were seen in plasma norepinephrine (3.5-fold normal), renin activity (7.6-fold normal), vasopressin (twice normal), atrial natriuretic peptide (9.4-fold normal), growth hormone (10.7-fold normal), and cortisol (1.9-fold normal). After recovery, the PaO2 increased (50 +/- 3 mm Hg) and PaCO2 fell (45 +/- 4 mm Hg), and the patients became free from edema. All the body compartments returned toward normal, although they did not entirely reach normal values. Renal plasma flow increased significantly, and glomerular filtration became normal. Right atrial and pulmonary arterial pressures and pulmonary vascular resistance decreased (p less than 0.01). Cardiac output decreased but not significantly. Blood pressure increased but not significantly. However, systemic vascular resistance increased significantly to a normal value. CONCLUSIONS: We conclude that patients with edema due to chronic obstructive pulmonary disease have severe retention of salt and water, reduction in renal blood flow and glomerular filtration, and neurohormonal activation similar to that seen in patients with edema due to myocardial disease. However, unlike the latter, in chronic obstructive pulmonary disease cardiac output is normal, and systemic vascular resistance and arterial blood pressure are low. This probably is due to the vasodilator properties of hypercapnia. The consequent low arterial blood pressure may be the stimulus for the neurohormonal activation and retention of salt and water.
Adult↗
Effects of prolonged infusion of human alpha calcitonin gene-related peptide on hemodynamics, renal blood flow and hormone levels in congestive heart failure.
We have previously demonstrated that short-term infusion of calcitonin gene-related peptide (CGRP) has beneficial effects in congestive heart failure. The effects of prolonged infusion of CGRP on hemodynamic functions, plasma hormones and renal blood flow were studied in 9 patients with congestive heart failure (New York Heart Association class III or IV, ejection fraction less than 35%). Hemodynamic variables were measured at 30-minute intervals for 8 hours during CGRP infusion (8 ng/kg/min) and for 2 hours after discontinuation. CGRP caused a decrease in right atrial (28%, p less than 0.05), pulmonary artery (22%, p less than 0.02), pulmonary artery wedge (37%, p less than 0.001) and systemic arterial (18%, p less than 0.05) pressures. Systemic vascular resistance decreased more than pulmonary vascular resistance. Cardiac output (72%, p less than 0.001) and stroke volume (60%, p less than 0.02) increased. Heart rate did not change. There was no evidence of tolerance throughout the infusion. The hemodynamic effects were lost within 30 minutes of stopping CGRP. Renal blood flow (34%, p less than 0.01) and glomerular filtration rate (43%, p less than 0.01) increased. Atrial natriuretic peptide decreased (p less than 0.05), while plasma cortisol (p less than 0.02) increased. Plasma epinephrine, norepinephrine, renin activity, aldosterone and growth hormone were unchanged. It is concluded that in patients with severe congestive heart failure, CGRP has sustained beneficial effects on hemodynamic functions and has no adverse effects on hormones. Unlike many other vasodilators, CGRP also increases renal blood flow and glomerular filtration.
Calcitonin Gene-Related Peptide↗
Ten to fourteen residue peptides of Alzheimer's disease protein are sufficient for amyloid fibril formation and its characteristic x-ray diffraction pattern.
The molecular basis of fibril formation in Alzheimers disease was explored by electron micrographic and x-ray diffraction analysis of a series of synthetic peptides corresponding to portions of the amino acid sequence of beta protein and that of its putative precursor. A minimum 14 residue peptide was identified that formed typical amyloid fibrils under physiological conditions. Of these 14 residues, 10 were sufficient to give an identical 4.76 A and 10.6 A diffraction pattern as that recently described for isolated neurofibrillary tangles, amyloid plaque cores and leptomeningeal amyloid fibrils.
Alzheimer Disease↗
Effect of phencyclidine on the metabolism of individual brain proteins.
The effect of phencyclidine on the metabolism of a selected number of rat brain proteins was determined using two-dimensional gel electrophoresis and quantitative fluorography. When rats were injected with phencyclidine, modulation of individual protein metabolism occurred in the pituitary and cortex. That is, a few proteins showed increased and others decreased incorporation of [35S]methionine, whereas total protein metabolism was unaltered. In contrast, in vitro treatment of brain tissue with phencyclidine inhibited incorporation of radiolabel into all proteins by approximately 50%, as shown by quantitative fluorography of individual proteins.
Animals↗
Nonstatic radiating spheres in general relativity.
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Journal Article↗
Fluorescence characterization of the low pH-induced change in diphtheria toxin conformation: effect of salt.
We have examined the effect of pH on diphtheria toxin conformation using intrinsic protein fluorescence and a new fluorescence quenching method. In aqueous solutions, fluorescence indicates toxin conformation undergoes a drastic change at low pH. This conformational change is closely associated with a switch from a hydrophilic conformation to a hydrophobic one, as judged by quenching-detected detergent binding. In the absence of NaC1 these changes occur around pH 4-4.5. However, in 150 mM NaCl the conformational change occurs in the pH 5-5.5 range, close to the pH the toxin is expected to encounter in endosomes and lysosomes. Therefore, the conformational change observed at low pH is likely to be physiologically significant.
Diphtheria Toxin↗
Reliability of two-dimensional echocardiography in diagnosing fungal endocarditis.
Although the techniques of M-mode and two-dimensional (2D) echocardiography (echo) have been found to be useful in patients with bacterial endocarditis, the 2D findings of fungal endocarditis are not known. In this report, we present the case of a young female narcotic addict with Candida albicans endocarditis in whom we diagnosed a large vegetation by 2D echo. Decision for surgery was made solely on the basis of the 2D-echo findings. We feel that 2D-echo findings are reliable in diagnosing fungal endocarditis because, with this technique, the size, shape, mobility, and exact location of the vegetation can be better identified than by the M-mode echo. In addition, early diagnosis of fungal endocarditis helps in treating the patients with medical and surgical therapy which may result in lower mortality.
Adult↗
Usefulness of two-dimensional echocardiography in diagnosing right ventricular hypertrophy.
The purpose of this study was to evaluate the usefulness of two-dimensional echocardiographic (2D echo) measurements in diagnosing right ventricular hypertrophy (RVH). These measurements of the right atrium and the ventricle were made in 15 patients with right ventricular hypertrophy and in 11 normal subjects and were as follows: right atrium long axis 2.13 +/- 0.42 vs 1.36 +/- 0.11 cm/m2 (p less than 0.001); right atrium short axis 2.78 +/- 0.60 vs 2.06 +/- 0.26 cm/m2 (p less than 0.001); right atrial area 8.81 +/- 2.79 vs 4.00 +/- 0.33 cm2/m2 (p less than 0.001); right ventricular long axis 4.65 +/- 0.64 vs 3.27 +/- 0.49 cm/m2 (p less than 0.001); and right ventricular area 13.02 +/- 3.64 versus 6.19 +/- 0.74 cm2/m2 (p less than 0.001). The 2D echo right atrial area and long axis had a sensitivity and specificity of 100 percent in the diagnosis of right ventricular hypertrophy. We conclude that 2D echo is useful in the diagnosis of right ventricular hypertrophy.
Adolescent↗
Preliminary crystallographic investigation of the protein toxin from corynebacterium diphtheriae.
Crystals of diphtheria toxin have been obtained in vapor diffusion experiments from concentrated solutions of potassium tartrate as the precipitating agent. The crystals are trigonal with unit cell dimensions a = b = 97.90 A and c = 100.30 A. The space group is P31 12 or its enantiomorph. The unit cell contains 6 molecules of molecular weight 62,000 with 1 molecule/asymmetric unit. The crystals diffract beyond 2.8 A resolution and are able to withstand more than 100 h of x-ray exposure. The complete structure analysis is in progress.
Corynebacterium diphtheriae↗
The electrocardiogram in obesity.
The electrocardiographic abnormalities ascribed to morbid obesity were analyzed in a group of 144 patients without apparent clinical cardiovascular pathology and compared with a control group of 100 normal weight patients. Fifty-eight patients in the obese group were re-analyzed after significant weight loss and the electrocardiographic findings compared with their initial changes when they entered the program. The QRS voltage for the obese group was slightly lower than the voltage of the normal population; but in a significant number of the patients restudied after weight loss, the QRS voltage decreased (37 out of 58 patients). In inferolateral leads non specific flattening of the T wave was observed in the obese group (71/144); it became normal as they lost weight. The P and QRS axes of the obese group initially were within normal limits but more to the left; they moved slightly to the right, although still within normal limits as the patients lost weight. Two conclusions can be drawn from the study: a) low voltage is not a significant feature in the ECG of the obese and, b) the most consistent finding in obese patients is a flattening of the T wave.
Adolescent↗
The three-dimensional structure of the lysozyme produced by Streptomyces erythraeus.
Streptomyces erythraeus lysozyme is different in its amino acid composition, primary structure, and specificity from all other mammalian lysozymes. The structure of the crystalline enzyme has been determined by x-ray diffraction analysis to a resolution of 2.9 A using multiple isomorphous replacement. The primary structure of the enzyme is only partially known and therefore the electron density map has been fitted with all the atoms of the main polypeptide chain and some atoms of the side chain. The enzyme consists of three different domains, and about 18% of the structure has helical conformation. A comparison of the tertiary structure of the bacterial lysozyme with either the mammalian or phage lysozyme does not show any obvious similarities.
Amino Acids↗