A semiempirical expression for the gel electrophoretic mobility of supercoiled DNA.
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DNA, Superhelical↗
Biomedical subjects
A Lahiri
Publications and source records attributed to A Lahiri.
Can intravenous beta blockade predict long-term haemodynamic benefit in chronic congestive heart failure secondary to ischaemic heart disease? A comparison between intravenous and oral carvedilol.
Several studies in the past have shown the long-term beneficial effects of beta-blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard beta-blocker therapy. Carvedilol, a new, non-selective beta-blocking agent with concurrent alpha-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction less than or equal to 45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5-7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5-50 mg b.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Quantitative 111In antimyosin antibody imaging to predict the age of myocardial infarction.
To establish whether quantitative 111In antimyosin uptake can be used to predict infarct age, we studied the heart-lung ratio in 107 images from 90 patients at various intervals following a Q-wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. The HLR was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background. The ratio ranged from 1.26 to 3.87, and declined with increasing infarct age. Infarcts were classified on the basis of age as type I (less than 3 days old), type II (less than 14 days), and type III (less than 90 days). True positive and false positive rates (TPR and FPR), and test-likelihood ratio calculations were performed for HLR thresholds ranging from 1 to 4, for the three infarct types. A FPR of 0% and likelihood ratio of infinity was obtained at a HLR threshold of 2.3 for type I infarcts (TPR 40.8%); at a HLR threshold of 2 for type II infarcts (TPR 50.6%), and a threshold of 1.8 for type III infarcts (TPR 52.6%). The likelihood of each infarct type can be estimated directly from the HLR for values below the above thresholds. These results show that quantitative 111In-antimyosin imaging may be used to predict infarct age.
Antibodies, Monoclonal↗
Theoretical analysis of gel electrophoretic data for interaction of lysine rich histone with supercoiled DNA.
We demonstrate the possibility of using gel electrophoresis as a technique for the quantitative analysis of interaction of lysine rich histone with DNA. On the basis of theoretical framework for extended ligand binding to one-dimensional lattices such as DNA we have set up systems of equations which relate the ligand-to-DNA ratio to the observed gel migration distance of the complex. From the analysis of experimental data for gel electrophoresis of supercoiled DNA in the presence of lysine rich histones we have found that the observed variation of electrophoretic mobilities of the histone-DNA complexes at low histone-to-DNA ratios can be described by a non-cooperative binding behaviour. At this limit we have estimated the intrinsic binding constant to be of the order of 10(3) M-1.
DNA, Superhelical↗
Improvement in left ventricular function after rapid weight loss in obesity.
The effect of rapid weight reduction on left ventricular function and blood pressure was studied in 34 obese subjects, who all weighed more than 30% above their ideal body weight. Subjects with co-existing hypertension (N = 15) and proven coronary artery disease (N = 9) were included to assess contributions from these factors. Blood pressure (BP) was measured both indirectly and by direct ambulatory intra-arterial methods. Radionuclide ventriculography was performed at rest and at exercise, before and after dieting, which was supervised in hospital (daily intake 330 kCal day-1 for 4 weeks). Dieting induced a weight loss of (mean +/- SD) 9.6 +/- 3.5 kg (P less than 0.0001) in the whole group. The mean daytime intra-arterial blood pressure fell from 157 +/- 23/90 +/- 15 to 144 +/- 21/85 +/- 13 mmHg (P less than 0.0001). The fall in ambulatory intra-arterial diastolic blood pressure did not reach significance in the normotensive and ischaemic groups. The mean resting left ventricular ejection fraction (LVEF) in the whole group showed a significant reduction after weight loss from 61 +/- 10% to 56 +/- 6% (P less than 0.005). Although the individual groups showed a fall in LVEF, the effect was most marked in the hypertensive group, from 65 +/- 9% to 57 +/- 5% (P less than 0.002). Before dieting none of the groups achieved a 'normal' 5% rise in LVEF above basal in response to exercise, the hypertensive and the ischaemic groups both showing non-significant falls. This phenomenon was, however, reversed after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of carvedilol on ventricular arrhythmias.
Carvedilol is a nonselective beta-blocker with alpha-mediated vasodilating properties that has been shown to be effective in systemic hypertension, stable angina, and congestive heart failure (CHF). In this study, we studied the effects of carvedilol on premature ventricular contractions (PVCs) in 65 patients undergoing treatment with carvedilol (12.5-50 mg b.i.d.) for 4-8 weeks. Twelve patients had hypertension, 41 had stable angina, and 12 had CHF. Holter monitoring for 24 h was performed before and after active carvedilol therapy. Median PVCs per 24 h decreased from 25.5 to 6.0 (p less than 0.001, n = 52). Reduction in PVC activity occurred in 77% of patients, and 23% of patients with multifocal PVCs changed their morphology to unifocal. Nonsustained ventricular tachycardia was present in four patients before treatment; this was abolished in all patients. R-on-T PVC was present in six patients; it decreased in five and increased in one. New ventricular tachycardia (less than 8 beats) occurred in two patients, but QT prolongation was not noted in these patients. An improvement in Lown's classification occurred in 50% of patients. However, in the CHF group, the improvement in Lown's criteria was observed in 73% of patients. Carvedilol does not appear to possess proarrhythmic effects, and chronic therapy reduces PVC activity in a wide range of patients. This property of carvedilol is complementary to its hypotensive and anti-ischemic effects. In the CHF group, the beneficial effects of carvedilol on left ventricular function and hemodynamics may combine with the improvement in PVC activity to produce a significant improvement in mortality.
Adrenergic beta-Antagonists↗
Spontaneous variability of left ventricular ejection fraction assessed with the Cardioscint.
A miniature, non-imaging caesium iodide nuclear probe optically coupled to a photodiode (the 'Cardioscint') has been developed which, in conjunction with a modified personal computer, is capable of continuous on-line monitoring of left ventricular function and ST-segment level at the bedside. The purpose of this study was to assess the variability in ejection fraction over periods of time and to compare this variability with that of equilibrium gamma camera radionuclide ventriculography. Ten normal volunteers (nine male) of mean (S.D.) age 49 (10) years underwent semisupine radionuclide ventriculography using both gamma camera and Cardioscint in randomized order. The gamma camera recorded four consecutive acquisitions (mean of 7.2 min each) and the Cardioscint, using a 20 s acquisition time, recorded left ventricular function over 35 min per subject. The mean ejection fraction of the group by gamma camera was 52 (7)% and by Cardioscint was 54 (5)%. When the variability in ejection fraction by gamma camera was compared with the Cardioscint averaged over corresponding time periods (i.e. an average of 7.2 min), the mean coefficient of variation of the camera was 5.0% versus 2.9% for the probe system. Individual 20-s probe acquisitions over the total study duration (reflecting the short-term variability of the system) had a coefficient of variation of 5.1%. Thus the Cardioscint provides a stable continuous recording of ejection fraction. These volunteer data provide a basis for interpretation of data acquired in the clinical situation.
Adult↗
The influence of therapeutic blocking of Gp IIb/IIIa on platelet alpha-granular fibrinogen.
Recent evidence suggests that platelet alpha-granule fibrinogen (fg) is derived from the plasma pool. Since platelets from patients with Type I Glanzmann's thrombasthenia (GT) are deficient in intracellular fibrinogen (fg) it was hypothesized that Gp IIb/IIIa could mediate the uptake of fg. To study the potential role of Gp IIb/IIIa in intracellular fg trafficking, the influence of therapeutic blocking of Gp IIb/IIIa on platelet fg was studied in 12 patients with stable ischaemic heart disease. Patients were either given a single intravenous dose of the monoclonal antibody 7E3 Fab (n = 4) or a combination of bolus and continuous infusion up to 24 (n = 3), 36 (n = 3) or 96 h (n = 2). All patients showed grossly prolonged bleeding times with a significant reduction of ex-vivo ADP induced aggregation. Although, surface Gp IIb/IIIa binding sites were consistently reduced in all patients, there was a variable but delayed decrease in platelet fg relative to vWf:Ag in only six out of the 12 patients studied. The reduction in fg appeared dependent upon both dosage and duration of Gp IIb/IIIa blockade. The study provides further evidence for the novel role of Gp IIb/IIIa in the intracellular trafficking of fg to platelet and megakaryocytic alpha-granules.
Adult↗
Can intravenous beta-blockade predict long-term hemodynamic benefit in chronic congestive heart failure secondary to ischemic heart disease? A comparison of intravenous with oral carvedilol.
Several studies have demonstrated the long-term beneficial effects of beta-blockers in the treatment of congestive heart failure. Despite interest in this mode of therapy, clinical application of beta-blockers has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show improvements with standard beta-blocker therapy. Carvedilol, a new nonselective beta-blocking agent with concurrent alpha-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischemic heart disease. All had resting left ventricular ejection fraction less than or equal to 45% and were maintained on diuretic therapy. Acute hemodynamic measurements were made after administration of intravenous carvedilol (2.5-7.5 mg) and after chronic therapy for 8 weeks (12.5 to 50 mg b.i.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring, and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study (five were withdrawn). Symptomatic and hemodynamic improvements were demonstrated in 11 of the 12 patients after 8 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Clinical role of indium-111 antimyosin imaging.
Myocyte necrosis occurs in ischaemic, inflammatory and toxic heart diseases and can be detected by indium-111 antimyosin imaging. This allows a non-invasive evaluation of the site, extent and quantitation of the severity of myocardial necrosis. Simultaneous imaging of perfusion in patients with myocardial infarction allows the differentiation of necrosed and perfused areas and the varying degrees of mismatch and overlap, which has prognostic significance. 111In-antimyosin imaging is useful in the assessment of patients with unstable angina and in those for whom the diagnosis of infarction or unstable angina is not clear. In suspected myocarditis, a positive scan indicates the necessity for endomyocardial biopsy to confirm inflammation, whereas a negative scan makes the diagnosis of myocarditis unlikely. Antimyosin imaging is not useful as a marker of rejection in the 1 year post-transplant, but uptake after this period is associated with an increased rejection rate and is therefore an important tool in planning management strategies. Most patients on anthracycline treatment have demonstrable uptake, which is related to the cumulative dose and to the ejection fraction. Its role in this situation is as yet unclear. The use of new ligands and radioisotopes (99mTc) is likely to allow earlier imaging and produce improved quality.
Angina, Unstable↗
111In antimyosin antibody uptake is related to the age of myocardial infarction.
The intensity of 111In antimyosin uptake is related to the type (Q wave or non-Q wave), size, and location of an acute myocardial infarction. To determine whether the uptake intensity is also related to the infarct age, and to establish the time frame during which 111In antimyosin uptake occurs postinfarction, we studied a quantitative measure of uptake intensity, the heart-lung (HL) ratio, in 90 consecutive patients at various intervals following a Q wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. Uptake of antimyosin could be demonstrated up to 154 days postinfarction. The HL ratio was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background, and was 1.93 +/- 0.51 (mean +/- SD) overall. The ratio declined exponentially with increasing age of infarct. Using nonlinear regression analysis, 47% of the total variance of the HL ratio could be attributed to age alone (p less than 0.001). Sequential antimyosin imaging was performed in nine patients, with the first study between 4 and 15 days, the second between 50 to 100 days, and the third between 125 to 270 days after the onset of chest pain. The HL ratios were (mean +/- SD) 1.77 +/- 0.25 for scans between 4 and 15 days, 1.54 +/- 0.12 for scans between 50 and 100 days (p less than 0.02), and 1.42 +/- 0.16 (p less than 0.05) for scans between 125 to 270 days, further establishing the progressive reduction in 111In antimyosin uptake with age of myocardial infarction.
Adult↗
Specific binding of 99MTc-antimyosin to necrotic human myocardium: clinicopathologic correlations.
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Aged↗
The mental representation of lexical form: a phonological approach to the recognition lexicon.
We propose a psycholinguistic model of lexical processing which incorporates both process and representation. The view of lexical access and selection that we advocate claims that these processes are conducted with respect to abstract underspecified phonological representations of lexical form. The abstract form of a given item in the recognition lexicon is an integrated segmental-featural representation, where all predictable and non-distinctive information is withheld. This means that listeners do not have available to them, as they process the speech input, a representation of the surface phonetic realisation of a given word-form. What determines performance is the abstract, underspecified representation with respect to which this surface string is being interpreted. These claims were tested by studying the interpretation of the same phonological feature, vowel nasality, in two languages, English and Bengali. The underlying status of this feature differs in the two languages; nasality is distinctive only in consonants in English, while both vowels and consonants contrast in nasality in Bengali. Both languages have an assimilation process which spreads nasality from a nasal consonant to the preceding vowel. A cross-linguistic gating study was conducted to investigate whether listeners would interpret nasal and oral vowels differently in two languages. The results show that surface phonetic nasality in the vowel in VN sequences is used by English listeners to anticipate the upcoming nasal consonant. In Bengali, however, nasality is initially interpreted as an underlying nasal vowel. Bengali listeners respond to CVN stimuli with words containing a nasal vowel, until they get information about the nasal consonant. In contrast, oral vowels in both languages are unspecified for nasality and are interpreted accordingly. Listeners in both languages respond with CVN words (which have phonetic nasality on the surface) as well as with CVC words while hearing an oral vowel. The results of this cross-linguistic study support, in detail, the hypothesis that the listener's interpretation of the speech input is in terms of an abstract underspecified representation of lexical form.
Concept Formation↗
Influencing the B-Z switch in supercoiled DNA.
The effect of Z-binding ligands on the supercoiling threshold in the supercoil-induced B-Z transition has been examined from the point of view of a two-state model. Expressions have been derived for the determination of the shift in critical supercoil density in terms of the physical parameters of the DNA-ligand system. Representative calculations indicate that the stabilizing action of Z-binding ligands on the Z conformation in closed circular DNA depends largely on the binding characteristics of the ligand. Application of the theoretical data has been demonstrated using the experimental results reported by Lafer et al. (J. Biol. Chem. 261 (1986) 6438).
Base Composition↗
Effect of supercoiling on the melting characteristics of heteropolynucleotides.
Considering a supercoiled DNA molecule, having equal numbers of two distinct types of base-pairs, it has been shown theoretically that even for the extreme cases of mixing of the two types of base-pairs in a supercoiled DNA, the melting temperatures as well as the melting curves do not differ significantly. This indicates that these properties are practically independent of the detailed base sequence when the molecule is a covalently closed one and may be replaced by an equivalent homopolynucleotide whose binding energy is equal to the average base-pairing energy of the original DNA. This conclusion has been further supported by comparing the theoretical results with those obtained experimentally in the cases of polyoma DNA and phi X174 DNA. Finally, the effects of supercoiling on the cooperativity of melting and a few aspects of the differential melting characteristics of a supercoiled DNA have been discussed which provide a clear physical understanding of the process.
Chemical Phenomena↗
Prolonged hypotensive effect of OPC-13340: a new, once-daily calcium channel blocking drug.
The duration and magnitude of the hypotensive effect of a new, once daily dihydropyridine calcium channel blocking drug, OPC-13340, was assessed in 14 patients with essential hypertension during normal daily activities and programmed exercise testing. Intra-arterial ambulatory blood pressure (BP) monitoring was performed before and after one month's treatment. Mean reduction in day-time BP was 27/14 mmHg and night-time BP 18/11 mmHg (P less than 0.001 and 0.05 respectively). There was no change in heart rate throughout the 24 h. Satisfactory day-time control of systolic and diastolic BP using the drug as monotherapy was achieved in 58% and 88% of patients respectively, although adequate control of nocturnal systolic and diastolic BP occurred in only 54% and 50% of patients respectively. No postural hypotension occurred during tilt testing, and there was a significant reduction in the peak BP observed during both dynamic and isometric exercise. Side effects were mild and transient. Thus OPC-13340, given once daily, is an effective and well tolerated anti-hypertensive drug, with a prolonged 24-h action.
Adult↗
Circadian variation and blood pressure: response to rapid weight loss by hypocaloric hyponatraemic diet in obesity.
Ambulatory intra-arterial blood pressure was monitored in 15 obese hypertensive and 10 obese normotensive subjects weighing more than 30% of their ideal body weight. Measurements were taken before and after 1 month in hospital on a diet of 330kCal/day designed to ensure 34 g protein and 65 mmol sodium. Mean +/- s.d. body mass index in the whole group fell from 40.8 +/- 7.6 to 37.2 +/- 7.4 kg/m2 (P less than 0.0001). Daytime intra-arterial blood pressure fell from 176 +/- 19/102 +/- 14 to 162 +/- 16/95 +/- 14 mmHg (P less than 0.0005 and P less than 0.002) in the hypertensive group and from 141 +/- 15/82 +/- 5 to 131 +/- 13/79 +/- 4 mmHg (P less than 0.005 for systolic pressure) in the normotensive group. Circadian variation of systolic intra-arterial blood pressure comparing the mean daytime with the mean night-time blood pressure recordings showed a day-night difference of 27 +/- 10 mmHg in the normotensive group compared with 12 +/- 13 mmHg in the hypertensive group (P less than 0.01). This trend was reversed after weight loss, when the normotensive group showed a day-night difference of 20 +/- 13 mmHg compared with 18 +/- 17 mmHg in the hypertensive group. Thus, circadian variation of systolic intra-arterial blood pressure in the hypertensive group was significantly (P less than 0.01) reduced compared with the normotensive group prior to, but not after, weight loss. These data show that, in obese subjects, weight loss produced a significant reduction in ambulatory intra-arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗