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Biomedical subjects

S N Murthy

Publications and source records attributed to S N Murthy.

At least 55 records · Page 3Linked to original sources
PubMed1990

Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro.

Although the specific cause(s) of inflammatory bowel diseases (IBD) has not been identified, one theory suggests ischemia as the early event that occurs in IBD and reperfusion causes sustained release of oxyradicals, leading to inflammation and ulceration. In this study, we have confirmed that H2O2 in the concentration seen during ischemia/reperfusion is primarily responsible for cellular membrane damage in the rat colonic fragments in vitro. Hydrogen peroxide caused a time and dose-dependent increase in 6-keto-PGF1 alpha and TXB2 release. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was blocked (50%) by phospholipase A2 (PLA2) inhibitors quinacrine and dimethyleicosadienoic acid at 5 min. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was completely blocked by indomethacin, significantly blocked (69%) by nordihydroguiaretic acid, and completely blocked by catalase. Superoxide dismutase and uric acid failed to inhibit H2O2-stimulated 6-keto-PGF1 alpha release. Endogenous catalase inhibitors 3-aminotriazole and sodium azide further enhanced the release of 6-keto-PGF1 alpha stimulated by H2O2 by 29% and 73%, respectively. Xanthine-xanthine oxidase also increased 6-keto-PGF1 alpha release from the fragments by 110%. This release was not inhibited by superoxide dismutase and uric acid, but was completely inhibited by catalase. These studies suggest a direct effect of H2O2 on colonic fragments leading to submicroscopic cellular membrane damage and excess prostanoid production utilizing a PLA2/cyclooxygenase and catalase-sensitive pathway without the formation of toxic hydroxyl ions. The quick release of 6-keto-PGF1 alpha also suggests an early manifestation of H2O2-induced damage in rat colonic fragments.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Comparison of technetium 99m-phytate and technetium 99m-sulphur colloid in primary bone tumours.

Eleven patients with proven primary bone tumour (five Ewing sarcomas, six osteosarcomas) and two cases of metastatic bone involvement (primary other than bone) were investigated with 99mTc-phytate and 99mTc-sulphur colloid to compare the behaviour of the two radiopharmaceuticals at the tumour site. After intravenous administration of the respective radiopharmaceutical, imaging of the tumour site and its contralateral part was carried out at 15 min and 1 h intervals. The data were stored in our computer. Bone scanning was also carried out in all patients. 99mTc-phytate uptake was observed at the tumour site in ten cases. The 99mTc-sulphur colloid study revealed sparse or no significant uptake in eight cases. In two patients, with osteosarcoma 99mTc-sulphur colloid investigation showed uptake at the primary tumour site. However, the distribution pattern is different from that of 99mTc-phytate. No significant uptake of either 99mTc-phytate or 99mTc-sulphur colloid was observed in the two patients with metastatic skeletal disease. It may be concluded that the unusual accumulation of 99mTc-phytate at the tumour site is not due to any generalized reticuloendothelial phenomenon and that the radiopharmaceutical itself is responsible for this.

Adolescent↗
PubMed1990

Cross-linked A alpha.gamma chain hybrids serve as unique markers for fibrinogen polymerized by tissue transglutaminase.

Notwithstanding the high degree of amino acid sequence homologies between human factor XIIIa on the one hand and intracellular transglutaminases (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13) from guinea pig liver or human erythrocytes on the other, we find that the two sets of enzymes differ remarkably in the mode of cross-linking the same protein substrate--i.e., human fibrinogen. In the program of polymerization with factor XIIIa, production of the known gamma-gamma' homologous chain pairs is the dominant feature, whereas with either intracellular transglutaminase, a series of hitherto unidentified A alpha.gamma hybrid chain combinations, designated A alpha p gamma q (p and q = 1, 2, 3...), is generated and practically no gamma-gamma' dimers are formed. Two-dimensional electrophoresis is particularly useful for demonstrating the production of A alpha p gamma q structures by protein staining as well as by immunoblotting against specific antibodies to the A alpha and gamma chains of fibrinogen. These findings should aid in deciding whether the direct cross-linking of fibrinogen by transglutaminase might contribute to thrombotic processes in addition to the thrombin- and factor XIIIa-dependent pathway of clot formation.

Animals↗
PubMed1989

Uptake of 99mTc-phytate in osteosarcoma cases.

During routine liver spleen scintigraphic studies using 99mTc-phytate in patients with proven osteosarcoma, an unusual uptake of this radiopharamaeutical at the primary site was observed. In all, five cases have been investigated and we have observed the uptake of 99mTc-phytate at the primary tumor site. Early and delayed imaging showed persistant concentration of the radiopharmaceutical. Studies with 99mTc-sulfur colloid in one of the patients did not show any uptake at the tumor site.

Adult↗
PubMed1988

Cationic environment and secretin secretion in canine duodenal mucosa in vitro.

We examined the effects of the divalent cation calcium (Ca2+) and the monovalent cations potassium (K+) and sodium (Na+) and different modalities that affect the fluxes of these cations on immunoreactive secretin (IRS) secretion from canine duodenal mucosa in vitro. In the absence of extracellular Ca2+, the basal IRS secretion was inhibited by 29%. Increased uptake of Ca2+ by passive diffusion and facilitated uptake of Ca2+ by ionophore A23187 had no effect on basal IRS secretion. However, Ca2+ channel blocking agents, LaCl3 and verapamil, inhibited basal IRS secretion by 18 and 33% respectively. High concentrations of extracellular K+ caused a dose-dependent but delayed stimulation of IRS secretion. K+-stimulated IRS secretion was not neurally mediated. Similarly, 9-aminoacridine, which blocks K+ exchange, mimicked the effects of K+. Valinomycin (10(-6) M) inhibited both K+-stimulated and 9-aminoacridine-stimulated IRS secretion. In the absence of extracellular Na+, there was a delayed inhibition of both basal and K+-stimulated IRS secretion. These results suggest that changes in cationic environment are associated with alterations in the secretion of IRS. High extracellular K+ concentration is conducive, and the absence of extracellular Na+ and Ca2+ is inhibitory to IRS secretion.

Aminacrine↗
PubMed1988

Gastrin: levels and trophic action during advancing age.

Changes in antral and serum gastrin levels as well as gastrin (G) and somatostatin (D) cell density were examined in 4- to 16-mo-old Fischer-344 rats. In these rats, the responsiveness of the gastric mucosa to the trophic action of gastrin was also examined. It was observed that whereas serum gastrin levels declined steadily between 4 and 16 mo of age, antral gastrin levels rose sharply during this period. In the antrum of 16-mo-old rats, the density of G-cells, but not D-cells, was found to be lower than in their 4-mo-old counterparts. Thus, when D- to G-cell ratios were calculated, 16-mo-old rats revealed a 50% higher D- to G-cell ratio than the 4-mo-old animals. To assess the trophic action of gastrin, groups of 4-, 8-, and 16-mo-old rats were infused subcutaneously (osmotic minipump) with either saline or gastrin (G-17-I; 250 ng.kg-1.h-1) for 14 days. The gastric mucosa was assayed for thymidine kinase (an indicator of proliferative activity) and DNA and protein content. In the saline-infused rats, gastric mucosal thymidine kinase activity increased sharply between 4 and 16 mo of age without significantly affecting DNA or protein content (expressed as milligrams per 100 g of body weight), suggesting that the age-associated rise in proliferative activity is not accompanied by increased mucosal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Cross-linked polymers in the red cell membranes of a patient with Hb-Koln disease.

Membranes isolated from the red cells of a Hb-Koln patient were shown to contain appreciable amounts of N epsilon-(gamma-glutamyl)lysine, the characteristic product of the post-translational cross-linking of proteins by transglutaminase. Such an apparently irreversible fusion of membrane proteins may contribute to the membrane defect in Hb-Koln disease.

Adult↗
PubMed1987

Rise in plasma trimethyllysine levels in humans after oral lysine load.

Oral administration of 5 g of lysine to healthy male volunteers produced a marked and progressive rise in plasma trimethyllysine (TML) from 3 to 24 h after the lysine load. Urinary TML did not register a similar rise. Plasma and urinary carnitine also increased after the lysine load. A similar rise in TML or carnitine was not seen after a 5 g tryptophan load. This suggests that the effect is specific for lysine and is not a nonspecific consequence of amino acid load.

Administration, Oral↗
PubMed1987

Intimal response of saphenous vein to intraluminal trauma by stimulated angioscopic insertion.

Endothelial damage after simulated angioscopic insertion was evaluated in 22 dogs by radioimmunoassay of endogenous 6-keto-prostaglandin F1 alpha (stable product of prostacyclin produced by the endothelium) by means of a closed perfusion system and scanning electron microscopy. In 20 dogs, a 1.7 mm diameter polyethylene tube similar in size and physical characteristics to a commercially available angioscope was passed once into the distal venotomy site and out of the proximal venotomy site for a total distance of 15 cm in the left saphenous vein (group A) and 10 times in both directions in the right saphenous vein, destroying all valves (group B). The vein segments were examined immediately after simulated angioscopic insertion and at intervals of 2, 3, and 4 weeks. The remaining two dogs were used as control animals to establish baseline prostacyclin production. All veins were patent when harvested. Scanning electron microscopy revealed globular and contracted endothelial cells in some areas of group A veins, whereas partial longitudinal absence of endothelial cells was noted in group B veins. Intimal coverage was complete by 2 weeks in group A veins and between 3 and 4 weeks in group B veins. Prostacyclin synthesis of group B veins was significantly less than that of group A at day 1 and at 2 weeks after operation (p less than 0.05), reaching that of control vein synthesis by 4 weeks. This study suggests that simulated angioscopic trauma of the luminal surface of the canine saphenous vein had no negative effect on early patency.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Neurohormonal regulation of secretin secretion in canine duodenal mucosa in vitro.

We examined the effects of cholinergic, peptidergic and GABAergic agents on secretin secretion from canine duodenal mucosal explants incubated in organ culture media. Carbachol (10(-12) to 10(-4) M), atropine (10(-6) to 10(-4) M), hexamethonium (10(-6) to 10(-4) M), and somatostatin did not alter basal secretion of secretin. Somatostatin (10(-7) to 10(-8) M) inhibited secretin secretion stimulated by pH 4.5. Met, Leu and their D-ala2-analogs inhibited both basal and pH 4.5-stimulated secretin. Naloxone reversed the inhibition caused by met-enkephalin at pH 7.4. GABA (10(-9) to 10(-6) M) stimulated both basal and pH 4.5-stimulated secretin secretion. GABA-stimulated secretin secretion was neuronal in nature, bicuculline sensitive and was mediated via post ganglionic cholinergic neurons. GABA-stimulated secretin secretion was inhibited by both somatostatin and metenkephalin, suggesting that GABA-stimulated secretin secretion may be under the inhibitory control of peptidergic agents as well.

Animals↗
PubMed1984

Hemoglobin binds to the amino-terminal 23-residue fragment of human erythrocyte band 3 protein.

Hemoglobin, aldolase and glyceraldehyde 3-phosphate dehydrogenase are known to bind to the cytoplasmic domain of band 3 protein. Binding of glycolytic enzymes to band 3 protein is inhibited by its amino-terminal fragments. To precisely localize the sequence portion of band 3 protein to which hemoglobin binds and to see whether the same region of amino-acid sequence binds both hemoglobin and glycolytic enzymes, a simple, direct solid-phase binding assay was developed. Peptides generated from the 23-kDa fragment by trypsin, cyanogen bromide and mild acid hydrolysis were used as inhibitors to determine the minimal sequence structure involved in the binding of the 23-kDa fragment to hemoglobin. The shortest peptide which inhibits the binding of the 23-kDa fragment is an acid cleavage peptide containing the sequence positions 1 to 23. This sequence is unusual as 14 of its residues are negatively charged, it contains no basic residues and has its amino terminus blocked. Using aldolase, glyceraldehyde-3-phosphate dehydrogenase and hemoglobin as competitive inhibitors in the binding of 23-kDa fragment, the affinity of hemoglobin to this fragment appears several-fold weaker than that of both the enzymes. These findings demonstrate that glycolytic enzymes and hemoglobin bind competitively to the same polyanionic sequence region of band 3 protein.

Amino Acid Sequence↗
PubMed1983

Amino acid sequence of the N alpha-terminal 201 residues of human erythrocyte membrane band 3.

We have determined the amino acid sequence of the N alpha-terminal portion of band 3, the anion transport protein of the human erythrocyte membrane. The material analyzed was a 201-residue, 23,053-Da fragment cleaved from the cytoplasmic end of band 3 by S-cyanylation. The sequence had these notable features. 1) The N alpha-terminal region was extraordinarily acidic, second only to a segment of similar size from the sigma factor of Escherichia coli RNA polymerase. The first 33 residues contained 6 aspartic acid and 12 glutamic acid residues, no basic residue, and a blocked N alpha-amino group. 2) The first 11 residues of the protein had a striking resemblance to the following 11 residues. 3) In contrast to the acidic N alpha-terminal third, the COOH-terminal two-thirds of the 23,053-Da fragment had a predominantly basic character. The highly acidic character of the N alpha-terminal portion of band 3 accounts for the capacity of this part of the protein to bind glycolytic enzymes in a highly electrostatic fashion, presumably through interaction with their cationic substrate-binding sites.

Amino Acid Sequence↗
PubMed1983

Bile acid and pancreatic trypsin outputs are parallel during intraduodenal infusion of essential amino acids.

There is disagreement as to whether contraction of the gallbladder occurs simultaneously with secretion of pancreatic enzymes during food ingestion. One study that employed exogenous cholecystokinin (CCK) alone showed dissociation of total bile acids (TBA) and trypsin outputs, while another study that employed exogenous CCK plus secretin showed parallel outputs of TBA and trypsin. Since previous studies have suggested that intraduodenal infusion of essential amino acids (EAA) evokes pancreaticobiliary secretion similar to that observed with food ingestion, we infused increasing doses of EAA intraduodenally in 10 subjects with intact gallbladder and in 10 subjects with previous cholecystectomy and measured total bile acids and trypsin outputs serially. In subjects with intact gallbladder, increasing molar doses of EAA induced parallel increases of TBA and trypsin outputs. In subjects with previous cholecystectomy trypsin outputs during infusion of EAA were similar to subjects with intact gallbladder, but their TBA outputs remained constant during the entire infusion period. Serial concentrations of plasma secretin did not change during intraduodenal infusion of EAA. These observations suggest that the gallbladder empties bile in concert with secretion of pancreatic enzymes following food ingestion.

Amino Acids, Essential↗
PubMed1983

Basal motor activity of the distal colon: a reappraisal.

The significance of recent motor data on the distal colon in irritable bowel syndrome is obscured by methodological questions such as bowel preparation, variability and reproducibility of motor activity and segmental differences. Thirty subjects were studied after prior bowel cleansing with a water enema on two separate occasions 1 wk apart (10 with one bowel movement per day, 10 with two to three per week, and 10 with three to 12 per day). Two additional studies were performed in 10 of the subjects, one with and one without prior cleansing. The motility indices of the cleansed and unwashed colon were dissimilar. The motility index per 3 min varied markedly over 3 h, and the indices between the paired studies were rarely identical. Marked segmental differences were noted. The mean motility index per 3 min of the constipated and the diarrhea groups was significantly greater than that of normals only in the 15-cm segment. In view of these variables, caution should be exercised in the interpretation of basal motor activity of the distal colon.

Colon↗
PubMed1982

Effect of red cell membrane binding on the catalytic activity of glyceraldehyde-3-phosphate dehydrogenase.

Band 3, the anion transport protein of the human erythrocyte, provides the site of association of certain glycolytic enzymes with the membrane. We have now demonstrated that glyceraldehyde-3-P dehydrogenase is inhibited, reversibly and completely, when membrane bound. The inhibition was competitive with respect to NAD+ and arsenate, but was noncompetitive with glyceraldehyde-3-P. Peptide fragments containing the NH2-terminal 23 residues of band 3 also inhibited the enzyme and displaced it from ghosts. Thus, the red cell membrane binding site for glyceraldehyde-3-P dehydrogenase is the same as that for aldolase, the polyanionic NH2-terminal region of the band 3 polypeptide.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1982

Gastric and pancreatic function in patients with end-stage renal disease.

Gastroduodenal disease such as peptic ulcer and duodenitis is increased in patients with end-stage renal disease. Gastric hypersecretion of acid proposed as the underlying mechanism has been disputed because peptic ulcer has occurred even in those with normal or low gastric acid secretion. We studied the pancreatic exocrine secretion of bicarbonate (HCO3) and the concentration of plasma pepsinogens in addition to gastric acid secretion in 15 patients on chronic hemodialysis, 10 patients wih previous renal transplantation and compared them with 10 subjects without gastrointestinal or renal disease. We confirmed hypersecretion of gastric acid in renal disease. We confirmed hypersecretion of gastric acid in renal patients on chronic hemodialysis but not in transplant patients. In addition, we found basal but hyposecretion of HCO3 and hyperpepsinogenemia in both renal groups. These observations suggest that the high incidence of gastroduodenal disease in end-stage renal disease might, in part, be due to the simultaneous occurrence of gastric acid hypersecretion, basal hyposecretion of HCO3 by the pancreas, and hyperpepsinogenemia.

Adult↗