Biomedical subjects
Publications and source records attributed to K S Rao.
The presence of the hydroxy-aluminium polymer (Al13-(OH)24O4(H2O)12(7+)) was noticed inside synaptosomes when synaptosomes were incubated with Al(NO3)3 at neutral pH values. Dysprosium nitrate (Dy(NO3)3)--a shift reagent--facilities the identification of the Al13 species distinctly inside the synaptosomes. 27Al NMR was used as a tool to detect the Al13 complex inside and outside the synaptosomes.
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The usefulness of conducting DNA damage and repair studies in a postmitotic tissue like brain is emphasized. We review studies that use brain as a tissue to test the validity of the DNA damage and repair hypothesis of aging. As far as the accumulation of age dependent DNA damage is concerned, the data appear to overwhelmingly support the hypothesis. However, attempts to demonstrate a decline in DNA repair capacity as a function of age are conflicting and equally divided. Possible reasons for this discrepancy are discussed. It is suggested that assessment of the repair capacity of neurons with respect to a specific type of damage in a specific gene might yield more definitive answers regarding the role of DNA repair potential in the aging process and as a longevity assurance system.
Chronic hypobaric hypoxia induces a mild degree of pulmonary arterial hypertension with structural alterations in the peripheral portions of the pulmonary arterial tree of the native Andean highlanders. On the other hand, animals indigenous to high altitude do not show these changes and are adapted to hypobaric hypoxia. The small pulmonary arteries of seven native Himalayan highlanders were examined at autopsy and found to be thin-walled with no medial hypertrophy of the muscular pulmonary arteries or muscularization of the arterioles. These findings suggest that the Himalayan highlanders may be adapted to hypobaric hypoxia.
The data on binding of Al to different brain cells, namely astrocytes, neuronal cells and synaptosomes, indicated that Al interacts more with astrocytes than with neuronal cells and synaptosomes. This was confirmed by broadening of the linewidth at half height (v 1/2 Hz) of the Al peak, and also by the extent of inhibition of membrane-bound Na+,K(+)-ATPase activity.
With a view to identifying ligands that could be used as promoters of iron absorption, the affinity of a number of iron chelating agents and the efficiency with which they can donate iron to the brush border receptors has been studied. A number of organic and inorganic compounds were found to chelate iron and keep it soluble at pH 7.5 of the intestinal lumen. This ligand-bound iron was taken up by the intestinal brush border receptors with varying degree of efficiency; ascorbic acid being the most effective and EDTA and citrate the least effective in donating the chelated iron to the receptors. Several polyphosphate compounds, used as food additives, chelated iron and kept it in solution but showed moderate potency for donating iron to the receptors.
The present investigation shows the effect of alkaline pH on the structure-function relationship of lipase from wheat germ. There is a 70% decrease in lipase activity at pH 10.0, which decreases to 93% at pH 12.0 as compared to neutral pH activity (Rajendran et al. 1990). This change is shown to be as a result of loss of alpha-helical structure with a concomitant increase in aperiodic structure. The results with fluorescence spectra and tyrosyl ionization indicate gradual exposure of aromatic side chains of tyrosine and tryptophan to the bulk solvent along with the structural changes. The enzyme is in an extended form at alkaline pH with a volume change of - 1300 ml mol as also indicated by increase in reduced viscosity to 12.5 ml g and significant decrease in sedimentation coefficient. The kinetics of the reaction points to a cooperative pseudo first-order reaction as determined by stopped-flow kinetic analysis in the ultraviolet region. The inactivation mechanism appears to follow a two-step mechanism of a fast and a slow reaction.
DNA-repair capacity, by incorporation in vitro of [3H]thymidine into DNA of isolated neuronal cells and splenic lymphocytes of rat was studied as a function of age. The incubations were carried out both in the presence and absence of hydroxyurea (HU), a known inhibitor of replicative DNA synthesis. The results indicate that neurons, unlike lymphocytes, obtained from adult and old animals offer a good model system to measure the DNA-repair process without any possible interference of DNA replicative synthesis. Further, the 'spontaneous' DNA repair by unscheduled DNA synthesis (UDS) in old neurons remained unchanged as compared to the adult level. However, the response of aging neurons, in contrast to that of young and adult neurons or of lymphocytes of any age, to a mutagenic challenge like UV light is limited. It is suggested that this lack of responsive DNA-repair against a given damage may lead to a general metabolic deterioration and senescence.
A simple technique has been used to correct the clawing of fingers in patients with Hansen's disease. The distal part of the palmar plate is excised and the remaining portion is advanced and sutured with a single horizontal mattress suture to prevent hyperextension of the metacarpophalangeal joint. A pulley advancement is also done. One hundred five claw hands were corrected in 99 patients from December 1985 to September 1988. Follow-up period varied from 6 months to 3 1/2 years. The results were assessed for correction of deformity, power grip, motion, and function. Out of 94 hands that were followed up after operation, power grip remained static in most cases. Correction of deformity was satisfactory in 85 hands, motion and function of the fingers were satisfactory in 63 hands, and correction of the clawing was statistically significant in two fingers (p less than 0.01).
"Bound" and "free" RNA polymerase activities were assessed in the nuclear fraction of cerebral cortical, neuronal, astroglial, and oligodendroglial cells obtained from rats of young, adult, and old ages. Significant decreases in both the bound and free polymerase II activities were noticed in old brain, as compared to adult brain, in neuronal and oligodendroglial nuclei. In astroglia, only the free polymerase II was found to be affected. No effect of aging could be seen on the activity of bound RNA polymerase I + III. The free RNA polymerase I + III activity was increased from adult to old age in neuronal nuclei, but unchanged in oligodendroglial and astroglial nuclei. The age-dependent reduction in RNA polymerase II was maximum in oligodendroglial cells, whereas it was least, although still significant, in neuronal cells. DNA isolated from old brain was unable to enhance the transcriptional activity when added to chromatin preparations obtained from rat brains of any of the above ages and the "old" chromatin was unable to accept even the "young" DNA as additional exogenous template. It is concluded that the reduced gene expression noticed in old brain nuclei is due to both altered chromatin/DNA structure and inadequate levels of free RNA polymerase II.
1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved.
Annual concentrations of toxic air contaminants are of primary concern from the perspective of chronic human exposure assessment and risk analysis. Despite recent advances in air quality monitoring technology, resource and technical constraints often impose limitations on the availability of a sufficient number of ambient concentration measurements for performing environmental risk analysis. Therefore, sample size limitations, representativeness of data, and uncertainties in the estimated annual mean concentration must be examined before performing quantitative risk analysis. In this paper, we discuss several factors that need to be considered in designing field-sampling programs for toxic air contaminants and in verifying compliance with environmental regulations. Specifically, we examine the behavior of SO2, TSP, and CO data as surrogates for toxic air contaminants and as examples of point source, area source, and line source-dominated pollutants, respectively, from the standpoint of sampling design. We demonstrate the use of bootstrap resampling method and normal theory in estimating the annual mean concentration and its 95% confidence bounds from limited sampling data, and illustrate the application of operating characteristic (OC) curves to determine optimum sample size and other sampling strategies. We also outline a statistical procedure, based on a one-sided t-test, that utilizes the sampled concentration data for evaluating whether a sampling site is compliance with relevant ambient guideline concentrations for toxic air contaminants.
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A high-performance liquid chromatographic procedure, including sample pretreatment, is presented for the analysis of the experimental antitumour drug vintriptol in plasma. The sample pretreatment involved liquid-liquid extraction of the buffered (pH 3) sample with chloroform. Vinblastine was used as internal standard. Separation was achieved on a Hypersil ODS (5 microns) column with a mobile phase of acetonitrile-phosphate buffer. Electrochemical detection (at +0.70 V) was used, giving a detection limit of 2 micrograms/l. The applicability of the assay was demonstrated in a pharmacokinetic study with eight cancer patients who received 45 or 50 mg/m2 vintriptol in a phase I study. A three-compartment model was used to fit the plasma concentration-time curves. Pharmacokinetic parameters are presented.
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Fine needle aspiration cytology was performed on 121 occasions in 100 patients with various thoracic lesions. The investigation was performed chiefly with the help of straight and lateral chest skiagrams regardless of the size or depth of the lesion. The cellular yield was 87.6%. Positive diagnosis of malignancy could be made in 50 cases. The histopathological correlation in malignant cases was 80%. Non-malignant cytology including neoplastic and inflammatory pathology was also found useful in patient management. This report highlights the versatile role of this procedure in arriving at a diagnosis and planning the treatment for malignant as well as non-malignant thoracic diseases.
An experiment was conducted to determine the influence of dietary Ca (2, 4, and 6%) and P (.3 and .6% total) on urinary Ca and pH and on plasma Ca++ and inorganic P (Pi) in commercial Leghorn hens. Urine (six hens per treatment) or blood (eight hens per treatment) was collected from hens at 0, 7, 14, and 21 h postoviposition on Days 3 and 10 after its introduction to treatment diets. Low dietary P reduced (P less than or equal to .05) plasma Pi concentrations. The lowest concentration of dietary Ca reduced (P less than or equal to .05) plasma Ca++. Urinary pH and Ca were lowest at 14 h after oviposition. Increasing dietary Ca from 4 to 6% had no influence on urinary Ca excretion when the diet contained .6% P. However, when the diet contained 4% Ca, lowering dietary P (from .6% to .3%) increased urinary Ca significantly. Increasing dietary Ca to 6% in the presence of low dietary P further elevated urinary Ca. Urine was acidic with all diets except with that containing 6% Ca and .3% P at 14 h after oviposition. Results indicate that low dietary P has a greater influence on elevating urinary Ca in laying hens than excess dietary Ca.
Three experiments were conducted to determine the possible interaction of particle size, in vitro limestone solubility rate, and the Ca status of the hen, respectively, with dietary Ca level and in vivo Ca solubilization in laying hens. The in vivo Ca solubilization in hens was determined by subtracting Ca recovered as limestone in the excreta (by repeated washing) from Ca fed as limestone. Limestones of two different particle sizes [.5 to .8 mm (small) versus 2 to 5 mm (large)] with the same in vitro solubility rates were used in Experiment 1. Limestones of two different in vitro solubility rates (4 versus 10%/15 min in .079 N HCl) with the same particle size in Experiment 2 were assessed for in vivo Ca solubilization. In both experiments, laying hens were fed diets containing graded levels of Ca: 1.5, 3.0, 4.5, and 6.0%. In Experiment 3, hens fed a Ca-deficient (1%) diet for 1 wk were compared with hens fed a diet containing 3.75% Ca to assess in vivo Ca solubilization as influenced by graded dietary Ca levels: 1.5, 3.0, and 4.5% Ca. In vivo Ca solubilization in hens was influenced (P less than .05) by dietary Ca level (inverse relationship), limestone particle size (large particle greater than small particle), and Ca status of hens (Ca-deficient hens greater than normal hens). In vivo Ca solubilization in laying hens, for the particle size tested, was not influenced by in vitro limestone solubility rate.(ABSTRACT TRUNCATED AT 250 WORDS)