Ischemic optic neuropathy after liver transplantation.
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Adult↗
Biomedical subjects
R Pai
Publications and source records attributed to R Pai.
Haemangiopericytoma--an unusual tumour--a report of 5 cases.
Haemangiopericytoma (HPC) has remained a controversial entity ever since its first description. The main histological criterion to diagnose this entity is the characteristic vascular pattern highlighted by the reticulin stain. Since this pattern can be present in several other connective tissue tumours, it is basically a diagnosis of exclusion. Electron microscopy has however been helpful in some cases.
Adolescent↗
Rapid assay for detection of chloramphenicol acetyl transferase in Haemophilus influenzae.
BACKGROUND & OBJECTIVES: Haemophilus influenzae causes a variety of life threatening infections in humans. Early detection of antimicrobial resistance is of importance in the treatment and management of infection. The modified Slack's method, a simple assay, has been evaluated in this study for the early detection of chloramphenicol resistance. METHODS: Fifty isolates of H. influenzae from invasive and non-invasive sites were included. Antimicrobial susceptibility testing was done by disc diffusion method and minimum inhibitory concentration (MIC) determination was performed for chloramphenicol only. Modified Slack's method was used to test for the production of chloramphenicol acetyl transferase (CAT). RESULTS: Invasive isolates showed higher degree of resistance to chloramphenicol (72%) compared to non-invasive ones (28%). One hundred per cent association was found between results of disc diffusion, MIC and CAT production amongst strains resistant to chloramphenicol. INTERPRETATION & CONCLUSION: The findings suggested that chloramphenicol still remains the drug of choice for treatment for non-invasive infection caused by H. influenzae. Modified Slack's method is a simple, rapid, inexpensive and reliable method for the detection of chloramphenicol resistance amongst H. influenzae.
Adult↗
Helicobacter pylori vacuolating cytotoxin (VacA) alters cytoskeleton-associated proteins and interferes with re-epithelialization of wounded gastric epithelial monolayers.
In previous studies, we demonstrated that Helicobacter pylori vacuolating cytotoxin (VacA) inhibits gastric epithelial cell proliferation and inhibits epidermal growth factor (EGF)-activated signal transduction. Cell proliferation and migration, both essential for mucosal healing are dependent on the cell cytoskeleton. Other investigators demonstrated that VacA induces vacuolation of eukaryotic cells. Since in some cells, control of actin cytoskeleton involves GTP-binding proteins of Rho family, in this study we examined whether VacA affects wound re-epithelialization, cell cytoskeleton-associated proteins Rho, Rac1 in a gastric epithelial (RGM1) cell monolayer wound model, and whether these changes correlate with vacuolation. VacA treatment significantly inhibited wound re-epithelialization, cell proliferation vs control. VacA-induced cell vacuolation strongly correlated with inhibition of wound re-epithelialization. Furthermore, VacA reduced Rac-1 protein expression and distribution, and C3-mediated ADP-ribosylation of Rho. These findings suggest that VacA may interfere with repair of gastric mucosal injury and ulcer re-epithelialization by altering cytoskeleton-dependent cell functions and signaling.
ADP Ribose Transferases↗
Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action?
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit angiogenesis in vivo and in vitro, but the mechanism of this action is unclear. Angiogenesis-formation of new capillary vessels-requires endothelial proliferation, migration, and tube formation. It is stimulated by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The cell cycle is regulated positively by cyclins and negatively by cyclin-dependent kinase inhibitors (CKI) and the retinoblastoma protein (pRb). Since the effects of NSAIDs on cell cycle-regulatory proteins in endothelial cells remain unknown, we examined the effect of indomethacin on bFGF-stimulated endothelial cell proliferation and on cell cycle regulatory proteins in rat primary aortic endothelial cells (RAEC). Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation. This inhibition correlated significantly with reduced cyclin D1 and increased p21 protein expression. Furthermore, indomethacin reduced pRb phosphorylation. These findings suggest that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels.
Animals↗
Sequential expression of adrenomedullin and its receptor during gastric ulcer healing in rats.
Adrenomedullin (AM) is a potent vasodilatory peptide. While its growth-regulating action in some cultured cells has been recognized, expression of AM and its receptor during gastric ulcer healing has not been explored. Specimens of gastric walls from control rats or gastric ulcers were obtained at 1, 3, 7, and 14 days after gastric ulcer induction. AM and its receptor mRNAs expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. By RT-PCR, AM mRNA was increased by 167% at three days, while AM receptor mRNA was increased by 234% at seven days (both P < 0.05). By in situ hybridization, AM and AM receptor mRNAs were increased at ulcer margin from three days after ulcer induction. By immunohistochemistry, AM was increased in the ulcer margin at three and seven days. In separate in vitro studies using a rat gastric epithelial (RGM1) cell line, AM treatment significantly increased transforming growth factor-alpha mRNA expression and cell proliferation.
Adrenomedullin↗
Expression of endothelin-1, and endothelin A and B receptors in portal hypertensive esophagus of rats.
Nitric oxide synthase is overexpressed in the portal hypertensive (PHT) esophagus, suggesting that expression of other vasoactive mediatora could also be affected. Therefore, in the present study we determined the expression of endothelin-1 (ET-1) and endothelin receptors, which could contribute to the regulation of the vascular tone in PHT esophagus. In esophageal specimens of PHT and sham operated rats, expression of ET-1 and its receptors A and B (ET(A)R and ET(B)R) mRNAs was studied by reverse transcription-polymerase chain reactions. ET-1 protein expression was assessed by immunostaining and enzyme immunoassay. In PHT esophagus, expression of ET-1, ET(A)R and ET(B)R mRNAs was significantly increased by 2.2-, 2.5- and 1.5-fold, respectively, compared with sham operated. The ET-1 protein was significantly increased by 2.2-fold vs. controls as measured by enzyme immunoassay. ET-1 protein was predominantly localized to endothelia of submucosal veins. Thus, portal hypertension induces over-expression of ET-1 in endothelia of esophageal submucosal vessels. Since ET-1 and its receptors could promote vascular proliferation and induce mucosal damage, the overexpressed ET-1 may play an important role in the development and rupture of esophageal varices in portal hypertension.
Animals↗
Systemic bacterial infections in bone marrow transplant patients.
The clinical microbiology department at CMC&H, Vellore in conjunction with the haematology department carries out routine surveillance of patients admitted to the hematology department. Since 1994 in a sample population of 55 patients with various underlying clinical conditions who have had bone marrow transplant, sepsis was observed in 16 patients (29%). The predominant Gram negatives associated with sepsis were non-fermenting Gram negative bacilli and all the 5 Gram positives were coagulase negative staphylococci. These organisms were susceptible to most of the routinely used antimicrobial agents. Continued surveillance is needed to determine changing trends with respect to organisms causing systemic infections and their susceptibility to antimicrobials.
Adolescent↗
Helicobacter pylori vacuolating cytotoxin (VacA) disorganizes the cytoskeletal architecture of gastric epithelial cells.
Helicobacter pylori colonization of the gastric mucosa induces peptic ulcer disease and interferes with ulcer healing. Re-epithelialization is an essential component of ulcer healing. It requires cell migration and proliferation which are dependent on the cell cytoskeleton. Most H. pylori strains produce a toxin (VacA) that induces multiple structural and functional changes in epithelial cells. In this study, we investigated the effects of VacA on the gastric epithelial cell cytoskeletal architecture. Exposure of rat gastric epithelial cells to purified VacA from H. pylori 60190 significantly inhibited actin stress fiber formation (83 +/- 5% reduction; p < 0.0001) and disorganized microtubule pattern (90 +/- 8%; p < 0.001). Furthermore, VacA treatment significantly reduced tyrosine phosphorylation of focal adhesion kinase (FAK) (by 45 +/- 6%; p < 0.002) and its expression in focal adhesions (73 +/- 8%; p < 0.0001). These findings suggest that H. pylori VacA interferes with cytoskeleton-dependent cell functions and with the transmission of signals related to cell spreading and growth.
Actin Cytoskeleton↗
Activation of Raf-1 during experimental gastric ulcer healing is Ras-mediated and protein kinase C-independent.
Our previous study demonstrated increases in epidermal growth factor receptor (EGF-R) phosphorylation and receptor tyrosine kinase and extracellular signal-regulated kinase (ERK1 and ERK2) activities in the ulcer margin of experimental gastric ulcer during healing. However, the intermediate steps linking activated receptor tyrosine kinase to ERKs during ulcer healing are as yet unknown. Raf-1 is upstream of mitogen-activated protein kinases (MAPK/ERK) and can be activated by Ras-dependent and/or Ras-independent mechanisms. Therefore, we studied Raf-1 activity, its potential activators protein kinase C (PKC) and Ras, and expression and associations of adapter proteins Shc, Grb2, and Sos during experimental gastric ulcer healing. To investigate if Raf-1-ERK activation is attributable to the epithelial component of ulcer margins, we studied the effect of EGF on PKC, Ras, and ERK activities in a rat gastric epithelial cell line (RGM1). Our results demonstrate that gastric ulceration significantly increases Raf-1 kinase activity, Grb2 and Ras protein, and Shc-Grb2 and Grb2-Sos complex levels. In contrast, PKC activity and protein level were significantly decreased in the ulcer margins. In RGM1 cells, EGF significantly increased Ras and ERK2 activities without affecting PKC activity. These findings indicate that Raf-1 activation during gastric ulcer healing is Ras mediated, involves Shc-Grb2-Sos, and is PKC-independent.
Animals↗
Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells.
BACKGROUND: Abnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular endothelial cells (ECs) and associated intracellular signaling mechanisms are not clearly understood. METHODS: In this study, we examined the effect of LDL and ox-LDL on intracellular signaling mechanisms associated with monocyte adhesion to glomerular ECs and intercellular adhesion molecule-1 (ICAM-1) expression. RESULTS: Ox-LDL, but not LDL, stimulated EC ICAM-1 expression and monocyte adhesion. Ox-LDL elevated protein tyrosine kinase (PTK) activity, and the preincubation of ECs with specific PTK inhibitors blocked ox-LDL-induced ICAM-1 message and monocyte adhesion. Whereas experimental maneuvers that inhibit either protein kinase C activation (by PKC depletion or with inhibitors) or Gi-protein-mediated pathways (pertussis toxin sensitive) had no effect on ox-LDL-induced monocyte adhesion and ICAM-1 expression. cAMP-elevating compounds did not induce ICAM-1 or monocyte adhesion. CONCLUSIONS: The data indicate that ox-LDL, by stimulating monocyte adhesion to the glomerular endothelium, may regulate monocyte infiltration within the glomerulus, supporting an early pathobiological role for atherogenic lipoproteins in glomerular injury. The results suggest that the activation of specific PTK and associated signaling may, at least in part, play a critical role in ox-LDL-mediated endothelial-monocyte interaction-related events. The data suggest that the interventions aimed at modifying associated intracellular signaling events within the glomerulus may provide potential therapeutic modalities in monocyte/macrophage-mediated glomerular disease.
Animals↗
HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway.
Although it is established that growth factors and prostaglandins function in the maintenance of gastric mucosal integrity and in the healing of gastric mucosal injury and ulceration, the regulatory relationship between growth factors and prostaglandins in the gastric mucosa is not well characterized. Therefore, we investigated whether hepatocyte growth factor (HGF) affects expression of COX-2 (the inducible form of the prostaglandin synthesizing enzyme, cyclooxygenase) in gastric epithelial cells and whether this action is mediated through the MAP (ERK) kinase signaling pathway. In RGM1 cells (an epithelial cell line derived from normal rat gastric mucosa), HGF caused an increase in COX-2 mRNA and protein by 236% and 175%, respectively (both P<0.05). This induction of COX-2 expression was abolished by pretreatment with the MAPK kinase (MEK) inhibitor PD98059. HGF also triggered a 13-fold increase in c-Met/HGF receptor phosphorylation (P<0.005) and increased ERK2 activity by 684% (P<0.01). Pretreatment with PD98059 abolished the HGF-induced increase in ERK2 activity, but not c-Met/HGF receptor phosphorylation. The specific inhibitor of p38 MAP kinase, SB203580, had no effect on HGF-induced COX-2 expression. Thus, HGF triggers activation of the COX-2 gene in gastric epithelial cells through phosphorylation of c-Met/HGF receptor and activation of the ERK2 signaling pathway.-Jones, M. K., Sasaki, E., Halter, F., Pai, R., Nakamura, T., Arakawa, T., Kuroki, T., Tarnawski, A. S. HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway.
Animals↗
Determination of penicillin resistance in Streptococcus pneumoniae and use of co-trimoxazole in treatment of pneumococcal pneumoniae.
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Anti-Bacterial Agents↗
Human DNase I contains mannose 6-phosphate and binds the cation-independent mannose 6-phosphate receptor.
DNase I isolated from human urine (hDNase) or expressed in Chinese hamster ovary (CHO) cells contains mannose-phosphorylated oligosaccharides. hDNase binds to a column of immobilized cation-independent mannose 6-phosphate receptor, with the strongest binding exhibited by the protein bearing diphosphorylated oligosaccharides. The binding is inhibited by 5 mM mannose 6-phosphate, and can be prevented by prior treatment of hDNase with alkaline phosphatase. Phosphorylated high-mannose oligosaccharides were observed at both sites of glycosylation in hDNase by high-performance liquid chromatography-mass spectrometry of a tryptic digest. These results indicate that hDNase, though not an acid hydrolase, may enter the lysosomal trafficking pathway, and may have evolved from a lysosomal enzyme.
Amino Acid Sequence↗
Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats.
Anti-tumor necrosis factor alpha (TNF-alpha) treatment decreases nitric oxide (NO) synthesis and ameliorates the hyperdynamic circulation in portal hypertensive rats. We have recently demonstrated that nitric oxide synthase isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that resultant NO overproduction probably is responsible for the increased susceptibility of the mucosa to damage. In the present study, we examined whether TNF-alpha is overexpressed in portal hypertensive gastric mucosa and whether anti-TNF-alpha treatment affects gastric NOS3 messenger RNA (mRNA) and protein expression. We examined plasma concentrations of TNF-alpha and its protein expression in gastric specimens from portal hypertensive and sham-operated rats using Western blotting and immunohistochemistry. We also measured gastric mucosal blood flow, gastric expression of NOS3 mRNA and protein, and NOS3 enzyme activity in rats with and without TNF-alpha-neutralizing antibody treatment. The TNF-alpha protein levels in portal hypertensive stomachs were significantly increased by 57% compared with levels in sham-operated controls. TNF-alpha antibody treatment normalized gastric mucosal blood flow in portal hypertensive stomachs and significantly reversed overexpression of gastric NOS3 mRNA, protein, and its enzyme activity in portal hypertensive rats by 48%, 45%, and 33%, respectively. These results suggest that TNF-alpha may regulate NOS3 expression in the portal hypertensive stomach and that anti-TNF-alpha treatment may ameliorate the pathophysiological abnormalities of portal hypertensive gastric mucosa.
Animals↗
Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats.
BACKGROUND & AIMS: Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers. METHODS: We studied EGF-R levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters. RESULTS: During the initial stages of healing (3 and 7 days), ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1 activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46 treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R phosphorylation, and ERK1 and ERK2 activity. CONCLUSIONS: These findings indicate that experimental gastric ulcer healing involves activation of EGF-R-ERK signal transduction pathway.
Animals↗
Induction of cyclooxygenase-2 in a rat gastric epithelial cell line by epiregulin and basic fibroblast growth factor.
Prostaglandins play an important role in maintaining gastric mucosal integrity. Cyclooxygenases (COX-1 and -2) are the key enzymes involved in prostaglandin synthesis. COX-2 expression in gastric epithelial cells remains a subject of controversy, and a possible regulation of gastric COX-2 by growth factors has not been explored. Therefore, we studied the effect of growth factors including epiregulin, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) on expression of COX-2 in a gastric epithelial cell line (RGM1) derived from normal rat gastric mucosa. Cells were incubated with 10 or 100 ng/ml of EGF. epiregulin, bFGF, or VEGF for 1, 2, 3, 6, and 24 h. COX-2 mRNA expression was determined by RT-PCR using specific COX-2 primers and COX-2 protein expression was determined by Western blotting. This study showed that COX-2 mRNA and protein are expressed in the gastric epithelial RGM1 cell line and that epiregulin and bFGF (but not VEGF) significantly increase expression of COX-2 mRNA and protein. Because PGs play an important role in mucosal defense, this study suggests that some growth factors contribute to maintaining mucosal integrity via activation of the COX-2 gene.
Animals↗
Translocation of MAP (Erk-1 and -2) kinases to cell nuclei and activation of c-fos gene during healing of experimental gastric ulcers.
We examined localization of extracellular signal regulated kinases (Erk) 1 and 2, and c-fos mRNA expression in normal and ulcerated gastric mucosa in rats at 1, 3 and 7 days after gastric ulcer induction. In normal gastric mucosa immunofluorescence signal for Erk-1 and Erk-2 was detectable in surface epithelial, neck and some glandular cells. In gastric mucosa of the ulcer margin, almost all epithelial cells displayed strong Erk-1 and Erk-2 immunoreactivity in the basolateral membranes and the cytoplasm. In addition 19+/-3% of cells showed nuclear localization of the Erk-1 and -2 signal. The c-fos mRNA expression was increased by 790+/-14% and 220+/-10%, respectively in gastric ulcer at 3 and 7 days after ulcer induction. Since in in vitro models nuclear translocation of Erk-1 and -2 triggers cell proliferation, our finding indicates relevance of this mechanism to gastric ulcer healing.
Animals↗