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Biomedical subjects

R Rajaram

Publications and source records attributed to R Rajaram.

At least 19 recordsLinked to original sources

Seasonal distribution of physico- chemical parameters in effluent discharge area of Uppanar estuary, Cuddalore, south-east coast of India.

Seasonal distribution of physico-chemical characteristics such as rainfall, pH, salinity, temperature, light extinction coefficient, dissolved oxygen, biological oxygen demand and nutrients like total phosphorus, inorganic phosphate, nitrite, nitrate and reactive silicate has been studied at two stations of Uppanar estuary in relation to effluent discharges from SIPCOT industries. There are 44 industries discharges their effluents into Uppanar estuary, which may influence the biota. Nutrient concentrations were higher during monsoon season and low during summer season. The mean concentrations of nutrients were high at station 1 than station 2 due to discharges from industries, coconut husk retting grounds near the station 1. In the present study, the physico-chemical characteristic of Uppanar estuary carried out and variations are discussed.

Agriculture↗

Surgical management of massive cerebellar infarction.

Massive cerebellar infarction accounts for less than 2% of strokes. Unlike massive hemispherical infarctions, in pure cerebellar infarctions, the prognosis is better. This case report discusses, a 61 year old lady who presented with atrial fibrillation and a massive cerebellar infarction. Timely surgical intervention reversed the deterioration in neurological status. The indications for surgical management, based on review of the literature, is presented.

Atrial Fibrillation↗

Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.

BACKGROUND: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. AIMS: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. PATIENTS: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. METHODS: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. RESULTS: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. CONCLUSIONS: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic value.

Adult↗

Apoptosis of lymphocytes in the presence of Cr(V) complexes: role in Cr(VI)-induced toxicity.

Cr(VI) compounds have been declared as a potent occupational carcinogen by IARC (1990) through epidemiological studies among workers in chrome plating, stainless-steel, and pigment industries. Studies relating to the role of intermediate oxidation states such as Cr(V) and Cr(IV) in Cr(VI)-induced carcinogenicity are gaining importance. In this study, issues relating to toxicity elicited by Cr(V) have been addressed and comparisons made with those relating to Cr(VI) employing human peripheral blood lymphocytes. Lymphocytes have been isolated from heparinized blood by Ficoll-Hypaque density gradient centrifugation and exposed to Cr(V) complexes viz. sodium bis(2-ethyl-2-hydroxybutyrato)oxochromate(V), Na[Cr(V)O(ehba)(2)], 1 and sodium bis(2-hydroxy-2-methylbutyrato)oxochromate(V), Na[Cr(V)O(hmba)(2)], 2 and Cr(VI). The phytohemagglutinin (PHA)-induced proliferation of lymphocytes has been found to be inhibited by the two complexes of Cr(V) and chromate Cr(VI) in a time- and concentration-dependent manner. Viability of cells decreases in the presence of Cr(V). Apoptosis appears to be the mode of cell death in the presence of both Cr(V) and Cr(VI). Pretreatment of cells with antioxidants before exposure to chromium(V) complexes reverse apoptosis partially. Possibility for the formation and implication of reactive oxygen species in Cr(V)-induced apoptosis of human lymphocyte cells has been indicated in this investigation. The intermediates of Cr(V) and radical species in the biotoxic pathways elicited by Cr(VI) seems feasible.

Antioxidants↗

Chromium(III)-induced structural changes and self-assembly of collagen.

Rat tail tendon (RTT) collagen has been reacted with a homologous series of chromium(III) complexes viz., (H2O)(4)Cr(OH)(2)Cr(H2O)(4+)(4) 1 (dimer), Cr(3)(OH)(4)(H2O)(5+)(9) 2 (trimer), and Cr(4)(OH)(4)(O2)(H2O)(4+)(12) 3 (tetramer), and the structural alterations brought about by these complexes have been investigated through atomic force microscopy (AFM) and circular dichroism (CD) studies. Examination of Cr(III)-treated tendons using AFM revealed changes in the D-periodicity of collagen, which may arise due to differences in the topological distribution of various Cr(III) complexes. Evidence for organisation of monomeric collagen into quarter staggered fibrils in the presence of Cr(III) dimer, 1, has been obtained. The quaternary structural changes induced by chromium in the protein have been correlated to the conformational changes of collagen in the absence of denaturation.

Acetic Acid↗

Inhibition of collagenase by Cr(III): its relevance to stabilization of collagen.

Bacterial collagenase has now been reacted with a select series of Cr(III) complexes and modifications in the activity of chromium-modified collagenase has been deduced from the extent of hydrolysis of (2-furanacryloyl-L-leucyl-glycyl-L-prolyl-L-alanine), FALGPA. A homologous series of Cr(III) complexes with dimeric, trimeric and tetrameric structures as in 1, 2 and 3 respectively has been investigated for their ability to inhibit the action of collagenase against FALGPA. Whereas competitive and non-competitive modes of inhibition of collagenase are expressed by 1, (dimer) and 2, (trimer) respectively, the tetramer, 3, exhibits poor affinity to collagenase and the inhibition of the enzyme activity is uncompetitive. Evidence for different modes of inhibition of collagenase depending on the nature of Cr(III) species has been presented in this work. Circular dichroism and gel electrophoresis data on Cr(III) modified collagenase corroborate the hypothesis that the inhibition of collagenase by the heavy metal ion arises from secondary and quaternary structural changes in the enzyme. The implications of the observed Cr(III) species specific inhibition of collagenase in gaining new insight into the mechanism of stabilization of collagen by Cr(III) are discussed.

Cations↗

Stabilization of chromium(V) species in bovine serum albumin adduct.

A detailed investigation of molecular interactions of the protein bovine serum albumin (BSA) with potassium dichromate has been made. Compelling evidence for the formation of a relatively stable Cr(V) species which decays only slowly to afford Cr(III) products has been obtained. The resulting final chromium(III) product mediates in cross-linking of BSA. The implications of the formation of a relatively stable chromium(V) as well as chromium(III)-mediated cross-links in the marker protein are discussed in the context of the metal ion-induced biotoxicity.

Animals↗

Chromium(III) hydrolytic oligomers: their relevance to protein binding.

The nature of chromium(III) complexes has been found to show a profound influence in its interaction with collagen. The hydrothermal stability of rat tail tendon (RTT) fibres treated with dimeric, trimeric and tetrameric species of chromium(III) has been found to be 102, 87 and 68 degrees C, while that of native RTT is 62 degrees C. This shows that the efficiency of crosslinking of collagen by chromium(III) species is dimeric > trimeric > tetrameric. This order of stabilisation is again confirmed by cyanogen bromide (CNBr) cleavage of RTT collagen treated with dimeric, trimeric and tetrameric chromium(III) species. CNBr has been found to cleave the collagen treated with tetrameric chromium(III) species extensively. On the other hand, dimer-treated collagen does not undergo any cleavage on CNBr treatment. The equilibrium constants for the reaction of a nucleophile like NCS(-) to the dimeric, trimeric and tetrameric species of chromium(III) have been found to be 15.7+/-0.1, 14.6+/-0.1 and 1.2+/-0.1 M(-1), respectively. These equilibrium constant values reflect the relative thermodynamic stability of the chromium(III) species-nucleophile complex. The low stabilising effect of the tetrameric species can be traced to its low thermodynamic affinity for nucleophiles.

Animals↗

Hydroxopentaamminechromium(III) promoted phosphorylation of bovine serum albumin: its potential implications in understanding biotoxicity of chromium.

Evidence for chromium(III) induced phosphorylation of a biomarker protein bovine serum albumin (BSA) is presented. Radiolabelled adenosine 5'-triphosphate (ATP) was reacted with BSA in the presence of various Cr(III) salts. While [Cr(NH3)5(H2O)]3+ brought about phosphorylation of BSA, several Cr(III) complexes, viz. [Cr(bpy)3]3+, [Cr(phen)3]3+, [Cr(en)3]3+, [Cr(salen)(H2O)2]+ and [Cr(salprn)(H2O)2]+, did not phosphorylate BSA. The Cr(III) mediated the transfer of gamma- and alpha-phosphates but not the adenine and the sugar moieties of the ATP molecule to BSA. The observed stoichiometry was 0.75 mol Pi to mol BSA for the gamma-phosphate and 0.5 mol Pi to mol BSA for the alpha-phosphate of ATP. The presence of serine phosphate and threonine phosphate was detected in the hydrolysate of phosphorylated BSA by means of comparison of Rf values with authentic samples of phosphoserine and phosphothreonine after chromatographic separation and autoradiography. [Cr(NH3)5(H2O)]3+ at pH 7.4 is known to exist as the conjugate base [Cr(NH3)5(OH)]2+ and is capable of ligand substitution involving metal-oxygen bond retention. Such anation reaction of [Cr(NH3)5(OH)]2+ with ATP subsequently leads to the esterification of alcoholic hydroxyl groups of serine and threonine of BSA. Possible consequences of chromium(III) induced in vivo phosphorylation of proteins are discussed.

Adenosine Triphosphate↗

Chromium(III) induced abnormalities in human lymphocyte cell proliferation: evidence for apoptosis.

The occupational hazards and respiratory problems of workers associated with the chromium related industries like mining, electroplating and tanning have received much focus. Although the cytotoxic and mutagenic effects of common chromium(VI) compounds are now established, to the best of our knowledge, this is the first report of apoptosis (programmed cell death) caused by a set of Cr(III) complexes in human lymphocyte cells. The effects of five Cr(III) complexes with differing ligand environment and structure as well as K2Cr2O7 on Phytohaemagglutinin (PHA) induced lymphocyte cell proliferation have been investigated. Two of the Cr(III) complexes and K2Cr2O7 are found to cause apoptosis of lymphocytes but not the others. A case for the importance of species specific effects rather than non specific metal oxidation state dependent processes has now been made.

Apoptosis↗

Nonenzymatic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose.

Nonenzymatic glycation by glucose (glucation) was compared with glycation by fructose (fructation). The rate and extent of protein-bound fluorescence generation upon fructation was about 10 times that upon glucation. In contrast, nonenzymatically glucated bovine serum albumin (BSA) released about twice as much formaldehyde upon periodate oxidation as did nonenzymatically fructated BSA. However, the rate of blocking of amino groups was similar in both proteins. Periodate oxidation of borohydride-reduced glycated BSA led to regeneration of amino groups with preservation of fluorescence. From the ratio between the decrease in formaldehyde-releasing ability and the regenerated amino groups, formaldehyde molar yields of 0.47 and 0.8 were computed for fructose- and glucose-derived Amadori groups, respectively. This is consistent with participation of both carbon 1 and carbon 3 in the Amadori rearrangement from fructose. The formaldehyde releasing ability of nonenzymatically fructated BSA attains asymptotic maximum values earlier than that of nonenzymatically glucated BSA. Thus, the higher rate of fluorescence generation in nonenzymatically fructated BSA could be explained by a faster conversion of its Amadori groups. Since fluorescence generation through the Maillard reaction has been correlated with long term complications of diabetes mellitus, the participation of nonenzymatic fructation in this pathological state deserves further exploration. This is especially relevant in tissues where fructose levels increase in diabetes as a result of the operation of the sorbitol pathway.

Chemical Phenomena↗

Insulin-dependent phosphorylation of GTP-binding proteins in phospholipid vesicles.

The involvement of GTP-binding proteins (G proteins) in insulin action has been investigated in an in vitro system. Insulin receptors that have been purified by wheat germ lectin chromatography and either tyrosine-agarose chromatography, sucrose density centrifugation, or insulin-Sepharose chromatography have been co-inserted into phospholipid vesicles with different purified G proteins. The results of these studies indicate that a specific insulin-promoted phosphorylation of two G proteins, Go and Gi, can occur in these phospholipid vesicles. Bovine retinal transducin is a poor substitute for Go and Gi, being only weakly phosphorylated by the insulin receptor, and bovine brain Gs is not a substrate. The phosphorylation of Gi and Go occurs primarily on the alpha-subunits. Under optimal conditions, about one alpha o- or alpha i-subunit is phosphorylated on a tyrosine residue for every two beta-subunits of the insulin receptor, suggesting a 1:1 interaction between these G proteins and the heterotetrameric (alpha 2 beta 2) insulin receptor molecular. The inactive (GDP-bound) form of the alpha-subunits appears to be the preferred substrate, with the phosphorylation being significantly reduced in alpha o and alpha i upon the binding of guanosine 5'-O-thiotriphosphate (GTP gamma S) and completely eliminated in the pure alpha-GTP gamma S complex of transducin. The Gi and Go proteins also cause an enhancement of the insulin-stimulated receptor autophosphorylation. This enhancement is a reflection of an increased incorporation of the insulin receptor into lipid vesicles which is induced by these G proteins. Taken together these results provide evidence for the interactions of G proteins with the insulin receptor in a lipid milieu.

Animals↗

An antibody directed against the carboxyl-terminal decapeptide of the alpha subunit of the retinal GTP-binding protein, transducin. Effects on transducin function.

An antibody (AS/7) prepared against the carboxyl-terminal decapeptide of the alpha subunit of transducin (alpha T) has been used in various reconstitution studies aimed at characterizing the role of the carboxyl-terminal domain in the different functional activities of transducin. The peptide-specific antibody is a potent inhibitor of the rhodopsin-stimulated GTPase activity in phospholipid vesicle systems containing pure rhodopsin and pure holo-transducin, or rhodopsin and the purified alpha T and beta/gamma (beta gamma T) subunit components, with the highest levels of inhibition (80-95%) occurring under conditions where the molar ratio of holo-transducin (or alpha T) to AS/7 approximately equal to 1. The inhibition of the receptor-stimulated GTPase does not represent an interference in the interactions between the alpha T subunit and the beta gamma T complex, since essentially identical levels of inhibition are observed when AS/7 is preincubated with either free alpha T, holo-transducin, or alpha T in the presence of excess beta gamma T, prior to assay. The AS/7-induced inhibition also does not appear to reflect an alteration in the ability of alpha T to bind or hydrolyze GTP and, in fact, the incubation of alpha T with AS/7 results in a stimulation of the intrinsic GTPase activity for alpha T alone (i.e. in the absence of rhodopsin). Thus, we conclude that the inhibition of the rhodopsin-stimulated GTPase activity by AS/7 is due to the direct blocking (by the antibody) of rhodopsin-alpha T interactions. While AS/7 is capable of uncoupling rhodopsin-transducin interactions, it appears to promote the stimulation of the cyclic GMP phosphodiesterase (PDE) by an activated alpha T subunit. Specifically, when the pure alpha T-guanosine 5-O-(3-thiotriphosphate) (alpha TGTP gamma S) species is preincubated with AS/7 prior to its addition to an assay solution containing PDE, there is at least a 4-fold increase in the resultant cyclic GMP hydrolysis relative to the activities measured with alpha TGTP gamma S, alone, or with alpha TGTP gamma S preincubated with nonimmune (control) rabbit IgG. The AS/7-induced promotion is specific for the active form of alpha T; the inactive alpha TGDP species does not stimulate PDE activity either in the presence or absence of the antibody. The different effects by AS/7 on the various activities of the alpha T subunit highlight the existence of distinct functional domains on alpha T.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

Administration of an aldose reductase inhibitor induces a decrease of collagen fluorescence in diabetic rats.

As a consequence of an increased flux through the sorbitol pathway fructose levels rise in various tissues in diabetes. Also, in vitro nonenzymatic fructosylation of protein induces the generation of fluorescence at a rate 10 times greater than glucosylation. The administration of sorbinil, an aldose reductase inhibitor known to lower tissue fructose concentration, to experimental diabetic rats led to a decrease in the fluorescence related to advanced Maillard products in their skin collagen. This effect is consistent with the in vivo occurrence of nonenzymatic fructosylation of collagen. A potential pathogenetic role for this posttranslational modification in diabetic complications should be considered.

Aldehyde Reductase↗

Vasculitis in Goodpasture's syndrome.

Because of differing diagnostic criteria, a controversy exists as to whether vasculitis may occur in patients with Goodpasture's syndrome. Using strict criteria (pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane antibody), we found histological evidence of vasculitis in two of 18 patients with Goodpasture's syndrome. The vasculitis was found in kidney biopsy specimens. Clinically, these two patients did not differ from other patients who have Goodpasture's syndrome without vasculitis. The presence of vasculitis should not exclude the diagnosis of Goodpasture's syndrome.

Adolescent↗