PubMed Health⌕ Search

Biomedical subjects

S Nagarajan

Publications and source records attributed to S Nagarajan.

72 records · Page 4Linked to original sources

Evidence for two cDNA clones encoding human GM2-activator protein.

Two cDNAs encoding GM2 activator, pGM2A (648 bp) and GAP (1093 bp), were isolated from human placenta lambda gt11 libraries. The DNA sequence of pGM2A from 1 to 302 was almost identical with GAP, but diverged from 303-648. PCR was used to demonstrate the presence of both species of GM2 activator in placental RNA. Both cDNAs hybridized to mRNAs of approximately 2.3 kb and to identical single bands on genomic Southern blots.

Amino Acid Sequence↗

Role of unsaturated derivatives of spermidine as substrates for spermine synthase and in supporting growth of SV-3T3 cells.

Synthetic unsaturated analogues of the natural polyamine were examined as possible substrates for spermine synthase and as replacements for spermidine in supporting the growth of SV-3T3 cells. It was found that N-(3-aminopropyl)-1,4-diamino-cis-but-2-ene [the cis isomer of the alkene analogue of spermidine] was a good substrate for spermine synthase, but that the trans isomer [N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and the alkene analogue [N-(3-aminopropyl)-1,4-diaminobut-2-yne] were not substrates. These results provide the first demonstration of stereospecificity in the spermine synthase reaction. All three of the unsaturated spermidine analogues described above and the cis-alkene analogue of spermine [N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene] were able to support the growth of SV-3T3 cells that were prevented from the endogenous synthesis of spermidine by treatment with alpha-difluoromethylornithine. Since N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and N-(3-aminopropyl)-1,4-diaminobut-2-yne were not converted into a spermine derivative, it is apparent that this conversion is not needed for the stimulation of growth. However, since N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene was also able to support growth and was not degraded to the spermidine derivative, it appears that either polyamine can be effective in this respect. All of the unsaturated analogues tested accumulated in the SV-3T3 cells to a much greater extent than spermidine itself. This indicates that these compounds are substrates for the polyamine transport system, but that they are less effective than the natural polyamines in the feedback regulation of this system.

Animals↗

Analgesic activity of Cassia alata leaf extract and kaempferol 3-o-sophoroside.

The analgesic activity of an extract of the leaves of Cassia alata and kaempferol 3-O-sophoroside were studied after intraperitoneal injection in mice and rats using the tail clip, tail flick, tail immersion and acetic acid-induced writhing methods and the results compared with morphine. Maximum analgesic activity of the extract was apparent 120 min after injection. Fifty milligrams of kaempferol 3-O-sophoroside appeared equivalent to 100 mg of the extract.

Analgesics↗

Studies of non-metabolizable polyamines that support growth of SV-3T3 cells depleted of natural polyamines by exposure to alpha-difluoromethylornithine.

A number of synthetic polyamine derivatives that included five achiral gem-dimethylspermidines and two analogous tetramethylated spermines were tested for their abilities to serve as substrates for enzymes metabolizing polyamines and for their capacities to substitute for the natural polyamines in cell growth. It was found that none of the compounds were effective substrates for spermine synthase, and only one, namely 8,8-dimethylspermidine, was a substrate for spermidine/spermine N1-acetyltransferase. However, all of the spermidine derivatives and 1,1,12,12-tetramethylspermine were able to support the growth of SV-3T3 cells in which endogenous polyamine synthesis was prevented by the addition of alpha-difluoromethylornithine. These results suggest that either spermidine or spermine can support cell growth without the need for metabolic interconversion. In contrast with the result with 1,1,12,12-tetramethylspermine, 3,3,10,10-tetramethylspermine did not restore growth of polyamine-depleted SV-3T3 cells. Comparison of the properties of these derivatives may prove valuable in understanding the physiological role of polyamines.

Acetyltransferases↗

Free fatty acids, lipid peroxidation, and lysosomal enzymes in experimental focal cerebral ischemia in primates: loss of lysosomal latency by lipid peroxidation.

Experimental focal cerebral ischemia was produced in monkeys (Macaca radiata) by occlusion of the right middle cerebral artery (MCA). The release of the lysosomal glycosidases, beta-D-hexosaminidase, alpha-L-fucosidase and alpha-D-mannosidase into the soluble fraction in the right basal ganglia of the experimental animals was measured at different periods from 30 min to 12 hr after occlusion and compared with the corresponding sham operated control animals. There was a significant increase in the released lysosomal enzymes in the MCA occluded animals at all periods and particularly at 4 hr after occlusion. The CSF from the experimental animals also showed elevated levels of hexosaminidase and fucosidase. The free fatty acids (FFA) measured in the basal ganglia at 30 min and 2 hr after occlusion showed a 100 fold increase in the experimental animals. The predominant fatty acid released was linoleic acid (18:2) followed by arachidonic acid (20:4). Lipid peroxidation in the basal ganglia measured by the thiobarbituric acid (TBA) reaction in the presence or absence of ascorbic acid also showed a significant increase in the experimental animals at all periods with a maximum at 30 min to 2 hr after occlusion. In order to assess whether lipid peroxidation causes damage to the lysosomes and release of the enzymes, a lysosome enriched P2 fraction from the normal monkey basal ganglia was prepared and the effect of peroxidation studied. Maximum peroxidation in the P2 fraction was observed in the presence of arachidonic acid, ascorbic acid and Fe2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of Cassia alata leaf extract on hyperglycemic rats.

The oral effectiveness of Cassia alata leaf extract on streptozotocin-induced hyperglycemia in rats has been studied and the results compared with glybenclamide. While the extract has no effect on glucose levels in normoglycemic animals, it reduced the blood sugar value in streptozotocin-induced hyperglycemic animals.

Animals↗

A heterogeneous beta-D-glucosidase activator from monkey parotid gland and its use as an affinity ligand in the purification of human salivary beta-D-glucosidase.

We have isolated a heat-stable, low molecular weight activator peptide(s) from monkey parotid gland that specifically activated human salivary beta-D-glucosidase. This activator appeared to be heterogeneous on Sephadex G-25 gel filtration and polyacrylamide gel electrophoresis under non-denaturing conditions. About 45% of the human salivary beta-glucosidase could bind to the activator immobilised on Sepharose and be eluted by Cutscum. The purified enzyme was nearly homogeneous, with a subunit Mr of 46,000 as revealed by SDS-gel electrophoresis and silver staining.

Animals↗

Spinal cord edema, 5-hydroxytryptamine, lipid peroxidation, and lysosomal enzyme release after acute contusion and compression injury in primates.

Physical and biochemical changes in the spinal cord of monkeys at 1/2, 2, and 4 hours following 200 g cm contusion injury and 50 g of compression injury and 2 hours of decompression following 4 hours of compression were studied. The pathophysiologic changes were milder in compression compared to contusion injury. Following contusion injury, at 1/2 and 2 hours there was significant increase in % water content, lipid peroxidation, and alpha-L-fucosidase. alpha-D-Mannosidase was significantly increased at all time periods, and beta-D-hexosaminidase was increased at 1/2 and 4 hours. At 4 hours following injury, serotonin (5 HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) showed a significant increase. From 10 minutes to 2 hours there was increased platelet aggregation. In compression injury, a significant increase in water content and 5 HT was observed only at 1/2 hour. Lipid peroxidation had increased at all time periods, whereas B-D-hexosaminidase, beta-D-galactosidase, and 5-HIAA were increased at 2 hours. alpha-D-Mannosidase had increased at 1/2 and 2 hours, and alpha-L-fucosidase had increased at 4 hours. After 2 hours decompression following 4 hours compression, water content, beta-D-galactosidase, and alpha-D-Mannosidase were significantly increased. An attempt was made to correlate the findings and to understand the sequential pathophysiologic changes in the first 4 hours following spinal cord trauma, providing a baseline for evaluation of the efficacy of any therapeutic maneuvers.

Acute Disease↗

Hepatic capillariasis.

The clinico-pathologic features of Capillaria hepatica infection in a 27-year-old Nigerian woman are discussed. This animal parasite has been encountered only rarely in humans. Less than 30 cases of human infection, mostly in children, having been recorded as far as the present authors are aware. This is the first case of hepatic capillariasis reported in West Africa. The pathologic features of this patient is marked by severe hepatic fibrosis, and this is correlated with disordered liver function. The possibility of histopathologic confusion with schistosomiasis mansoni is discussed.

Adult↗

Recognition of superpotent sweetener ligands by a library of monoclonal antibodies.

Monoclonal antibodies (mAb) made to the superpotent guanidino sweet tasting ligand, N-(p-cyanophenyl)-N'-(diphenylmethyl)-guanidineacetic acid were examined for their molecular recognition specificities using 14 different sweetener analogues in a competitive radioimmunoassay. The effects of variations in pH on ligand binding was also examined by radioimmunoassay. Photoaffinity labelling of the binding site was accomplished using a radiolabelled azido-derivative of the parent ligand, and L-chain or H-chain labelling was easily identified in several different mAb. For two of the mAb examined in this study (NC6.8 and NC10.14), the analogue binding studies are in agreement with the known Fab-ligand crystal structures. Monoclonal antibodies to this family of sweet tasting compounds may be useful probes for the study of sweet taste chemistry and identification of novel sweet taste ligands from combinatorial chemical libraries.

Acetates↗