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Biomedical subjects

S Chandra

Publications and source records attributed to S Chandra.

At least 127 records · Page 7Linked to original sources

Role of phosphorylation in elicitation of the oxidative burst in cultured soybean cells.

The oxidative burst is likely the most rapid defense response mounted by a plant under pathogen attack, and the generated oxidant species may be essential to several subsequent defense responses. In our effort to characterize the signal-transduction pathways leading to rapid H2O2/O2- biosynthesis, we have examined the role of protein phosphorylation in this resistance mechanism. K-252a and staurosporine, two protein-kinase inhibitors, were found to block the oxidative burst in a concentration-dependent manner. When added during H2O2 generation, the burst was observed to rapidly terminate, suggesting that continuous phosphorylation was essential for its maintenance. Importantly, phosphatase inhibitors (calyculin A and okadaic acid) were found to induce the oxidative burst in the absence of any additional stimulus. This may suggest that certain kinases required for the burst are constitutively active and that stabilization of the phosphorylated forms of their substrates is all that is required for burst activity. In autoradiographs of elicited and unstimulated cells equilibrated with 32PO4(3-), several phosphorylated polypeptide bands were revealed that could represent proteins essential for the burst.

Journal Article↗

Balloon mitral valvotomy in patients with systemic and suprasystemic pulmonary artery pressures.

Mitral stenosis with severe pulmonary artery hypertension constitutes a high risk subset for surgical commissurotomy or valve replacement. Balloon mitral valvotomy has been proposed as a technique for treating high risk surgical patients with mitral stenosis. The efficacy of this technique in patients with severe pulmonary artery hypertension, however, has not been fully evaluated. Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 450 consecutive patients. Of these, forty-five (10%) patients had systemic or suprasystemic systolic pulmonary artery pressures (110 +/- 20, range 96 to 170 mm Hg). The baseline characteristics and immediate hemodynamic results of these 45 patients with systemic/suprasystemic systolic pulmonary artery pressures (group I) were analysed and compared with those of 405 patients with subsystemic systolic pulmonary artery pressures (group II). Patients in group I were more symptomatic (New York Heart Association functional class > or = III, 96 vs. 55%, P < 0.001) and had severe subvalvular fibrosis (mitral subvalvular distance ratio [MSDR], 0.14 +/- 0.04 vs. 0.22 +/- 0.04, P < 0.01). Before PTMC, mean transmitral gradient was higher (34 +/- 8 vs. 25 +/- 4 mm Hg, P < 0.02) and mitral valve area smaller (0.5 +/- 0.3 vs. 0.9 +/- 0.4 cm2, P < 0.02) in group I patients, who also had higher pulmonary vascular resistance (16 +/- 5 vs. 9 +/- 5 U, P < 0.005). After PTMC final mean transmitral gradients (7 +/- 3 vs. 5 +/- 3 mm Hg) and mitral valve areas (1.9 +/- 0.4 vs. 2.0 +/- 0.4 cm2) were similar in both groups (P = NS). Group I patients had a greater decrease in pulmonary artery pressures (34 +/- 4 vs. 25 +/- 2%, P < 0.05) but final systolic pulmonary artery pressures (82 +/- 20 vs. 50 +/- 14 mm Hg) and pulmonary vascular resistance (12 +/- 4 vs. 6 +/- 4 U) remained significantly higher in this group (P < 0.005). Thus, in patients with severe pulmonary artery hypertension, PTMC is a safe and effective technique providing good immediate hemodynamic results.

Adult↗

Comparative tissue toxicity evaluation of four endodontic sealers.

The tissue toxicity of zinc oxide-eugenol, Tubli seal, Sealapex, and Endoflas F.S. was investigated by injecting them into the subcutaneous connective tissue of the dorsal surface of rats and studying the tissue response histologically. Animals were killed after time intervals of 48 h, 7 days, 14 days, 1 month, and 3 months; tissue sections were taken from the injection sites. Histological examination of the tissue sections revealed that all of the sealers caused some inflammation that decreased with time, except in the case of zinc oxide-eugenol where it increased from the 48th hour to the 7th day and after that showed a decreasing trend. Overall, Sealapex showed the least inflammatory reaction compared with other sealers used, because it showed moderate inflammation at 48 h that became mild in later periods. Zinc oxide-eugenol, Tubli seal, and Endoflas F.S. were severely toxic at 48 h and 7 days. This toxicity decreased gradually in later time periods. No inflammatory reaction was seen at 3 months with any of the sealers used.

Animals↗

Chloroquine encapsulated in malaria-infected erythrocyte-specific antibody-bearing liposomes effectively controls chloroquine-resistant Plasmodium berghei infections in mice.

The suitability of liposomes as drug carriers in the treatment of drug-resistant rodent malaria was examined after covalently attaching F(ab')2 fragments of a mouse monoclonal antibody (MAb), MAb F10, raised against the host cell membranes isolated from the Plasmodium berghei-infected mouse erythrocytes, to the liposome surface. The antibody-bearing liposomes thus formed specifically recognized the P. berghei-infected mouse erythrocytes under both in vitro and in vivo conditions. No such specific binding of the liposomes with the infected cells was observed when MAb F10 was replaced by another mouse monoclonal antibody, MAb D2. Upon loading with the antimalarial drug chloroquine, the MAb F10-bearing liposomes effectively controlled not only the chloroquine-susceptible but also the chloroquine-resistant P. berghei infections in mice. The chloroquine delivered in these liposomes intravenously at a dosage of 5 mg/kg of body weight per day on days 4 and 6 postinfection completely cured the animals (75 to 90%) of chloroquine-resistant P. berghei infections. These results indicate that selective homing of chloroquine to malaria-infected erythrocytes may help to cure the chloroquine-resistant malarial infections with low doses of chloroquine.

Animals↗

Golgi apparatus is involved in intracellular Ca2+ regulation in epithelial LLC-PK1 cells.

Several lines of evidence suggest that the Golgi apparatus is involved in Ca2+ regulation in renal epithelial LLC-PK1 cells. Laser scanning confocal microscopy (LSCM) was employed to establish that a prominent perinuclear region is occupied mainly by the Golgi apparatus in this cell line. LSCM measurements in individual cells with the ionized Ca2+ indicator calcium green revealed that stimulation of LLC-PK1 cells with arginine vasopressin (AVP) resulted in the elevation of ionized Ca2+ levels. However, the vasopressin-induced rise in ionized Ca2+ was attenuated if the Golgi apparatus was disassembled by pretreating the cells with brefeldin A (BFA). Subcellular measurements of total Ca2+ with ion microscopy in cryogenically prepared cells indicated that 1) within 1 min of AVP treatment significant quantities of sequestered Ca2+ were released from the perinuclear Golgi region and 2) the BFA treatment reduced the total Ca2+ stored in the Golgi region. These observations indicate that the Golgi apparatus is sensitive to hormonal stimulation and may play important roles in intracellular Ca2+ regulation in LLC-PK1 cells.

Animals↗

Improved safety from plasma derivatives: purification and viral elimination characteristics of mononine.

The occurrence of viral transmission with coagulation factor concentrates treated with a single virus elimination step has resulted in a consensus that multiple virus elimination steps must be incorporated in the processing of these proteins. As an example of this methodology, the steps included in the purification of the factor VIII concentrate Monoclate-P are reviewed and those used to purify the factor IX concentrate Mononine--monoclonal antibody chromatography, sodium thiocyanate incubation, and a novel ultrafiltration system--are described. Rigorous quality control/quality assurance during processing is essential. The ultimate safety of the product used clinically further requires monitoring of long-term stability and verification of the absence of neoantigens that could stimulate unusual levels of antibody formation. Standardization of regulatory compliance will further strengthen the safety of all products. The zeal to add further barriers to viral contamination should not compromise the timely assessment of these additional protections.

Antibodies, Monoclonal↗

Efficacy and safety of oral iron chelating agent deferiprone in beta-thalassemia and hemoglobin E-beta thalassemia.

OBJECTIVES: To assess efficacy and safety of oral iron chelating agent deferiprone (DFP) in patients with beta thalassemia and hemoglobin E-beta thalassemia. DESIGN: Non-randomized study. SETTING: Hematology Out-Patient Department. SUBJECTS: Forty-one patients of beta thalassemia and hemoglobin E-beta thalassemia. INTERVENTIONS: DFP was given to 20 patients, 10 patients of beta thalassemia and 10 with hemoglobin E-beta thalassemia; the rest were taken as controls. RESULTS: A significant fall in serum ferritin was observed in the study group along with rise in urinary iron excretion (p < 0.05). Adverse effects of DFP were nausea and vomiting (30%), significant arthropathy requiring stopping of the drug (30%), and reversible neutropenia in one patient. All these complications could be managed easily with medical supervision and no death or permanent disability was seen. CONCLUSIONS: DFP is an effective and fairly well tolerated oral iron chelating agent. The side effects that occur can be tackled easily if monitored properly.

Administration, Oral↗

Pulmonary valvuloplasty using Inoue balloon catheter.

We report balloon pulmonary valvuloplasty using the Inoue catheter in three patients with severe valvular pulmonic stenosis. The mean right ventricular systolic pressure and the pulmonary valvular peak to peak systolic gradients decreased from 140 +/- 23 to 40 +/- 26 mmHg (P < 0.001) and 120 +/- 26 to 8 +/- 8 mmHg (P < 0.001) respectively. This report suggests that pulmonary valvuloplasty using the Inoue balloon catheter technique is feasible, safe and effective.

Adolescent↗

Modified Inoue technique for a patient with giant left atrium.

Negotiating an Inoue balloon catheter into the left ventricle, in the presence of mitral stenosis, can present a problem when carried out on patients with giant left atrium. We report a manoeuvre to overcome this problem by utilizing the reverse double loop of an Inoue balloon catheter in the large left atrial cavity.

Adolescent↗

Imaging of total intracellular calcium and calcium influx and efflux in individual resting and stimulated tumor mast cells using ion microscopy.

Ion microscopy was employed to investigate intracellular total calcium concentrations and calcium influx, and efflux in resting and antigen-stimulated tumor mast cells (RBL-2H3 cells). The nucleus, a perinuclear region which included the Golgi apparatus (Golgi region), and the remaining cytoplasm were spatially resolved with the Cameca IMS-3f ion microscope in cryogenically prepared cells. In resting cells the nucleus contained about 0.60 mM, the Golgi region about 1.2 mM, and the remaining cytoplasm about 1.0 mM total calcium. Antigen stimulation of rat basophilic leukemia cells resulted in a significant loading of calcium in all three cellular compartments. Antigen stimulation in the absence of extracellular calcium resulted in a significant loss of total calcium from all three intracellular compartments. Influx and efflux of calcium were measured simultaneously in resting and stimulated cells by using stable 44Ca in the extracellular solution, and by imaging mass 40 to determine the native intracellular calcium (40Ca) and mass 44 to localize the 44Ca that entered the cell from extracellular solution. After a 10-min incubation, 0.240 fmol of the total calcium per cell had been replaced with 44Ca, which amounts to about 33% of the total cell calcium. If antigen was present during this incubation there was an additional loss of 0.229 fmol of 40Ca and an added gain of 0.476 fmol of 44Ca per cell, which corresponds to a net increase in total intracellular calcium of 0.247 fmol.

Animals↗

Percutaneous transvenous mitral commissurotomy for restenosis after surgical mitral valvotomy.

Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 350 patients. Of these patients, 51 (15%) (30 women and 21 men, aged 32 +/- 11 years) had restenosis 11 +/- 4 years following surgical valvotomy. Forty (79%) patients were in New York Heart Association (NYHA) class III and 11 (21%) were in class IV. PTMC resulted in an increase in mitral valve area from 0.82 +/- 0.3 to 1.9 +/- 0.2 cm2 (p < 0.001), an increase in cardiac index from 1.9 +/- 0.4 to 2.8 +/- 0.5 l/min/m2 (p < 0.001), and a decrease in mean transmitral gradients from 29 +/- 4 to 6 +/- 4 mmHg (p < 0.001). The results did not differ from those observed in 299 patients without prior surgical valvotomy. On univariate analysis, the subvalvular fibrosis, assessed angiographically, and the duration from prior surgery were not found to influence the overall outcome. At 24 weeks, 46 of 48 (96%) patients in whom clinical follow-up was available, were found to be in NYHA class I and 2 (4%) patients were in class II. Thus, PTMC is a safe and effective procedure for patients with mitral restenosis following surgical valvotomy.

Adolescent↗

Influence of subvalvular fibrosis on results and complications of percutaneous mitral commissurotomy with use of the Inoue balloon.

In 136 consecutive patients who underwent percutaneous transvenous mitral commissurotomy (PTMC) with use of the single rubber-nylon (Inoue) balloon Inoue balloon angiographically analyzed subvalvular fibrosis was assessed retrospectively with regard to results and complications. There were 53 males and 83 females, with a mean age of 22 +/- 11 years (range 10 to 48 years). For the entire group, mitral valve area increased from 0.7 +/- 0.3 to 2.1 +/- 0.6 cm2 (p < 0.001). Valve area increased from 0.7 +/- 0.12 to 1.8 +/- 0.14 cm2 in patients with severe subvalvular fibrosis (n = 55) and from 0.8 +/- 0.11 to 1.9 +/- 0.12 cm2 in cases with mild to moderate subvalvular fibrosis (n = 80; p = NS). The number of patients with 2+ or greater increase in mitral regurgitation was not different between the two groups (6% vs 5.5%, p = NS). None of the patients required mitral valve replacement immediately after PTMC. We conclude that, with use of the Inoue balloon, PTMC can be successfully performed in patients with severe subvalvular fibrosis.

Adolescent↗