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Biomedical subjects

N K Gupta

Publications and source records attributed to N K Gupta.

At least 55 records · Page 3Linked to original sources

Effect of type of resection on plasma granulocyte elastase levels following surgery for non-small cell lung carcinoma.

The lung is the primary focus of complications associated with adult respiratory distress syndrome (ARDS) and increased activation of granulocytes has been implicated in the genesis of ARDS. In the present study, plasma granulocyte elastase levels were measured in 24 patients undergoing lung resection for non-small cell lung carcinoma. Pre-, peri- and post-operative assessments of plasma elastase levels were made of patients who underwent a partial resection (lobectomy, n = 13) and patients who underwent a complete lung resection (pneumonectomy, n = 11). Preoperatively, values were similar for both patient cohorts and did not differ from those of normal volunteers. However, immediately (1 h) post-operation, elastase levels in patients who had undergone pneumonectomy were significantly elevated (300% of baseline value, P < 0.005), whereas levels were unchanged in lobectomy patients. On the 1st post-operative day (POD), elastase levels had returned to normal in pneumonectomy patients, whilst lobectomy patients now exhibited increased plasma elastase levels which remained marginally increased until the time of discharge (P < 0.05). The determinants of granulocyte activation following lung resection remain to be elucidated but may potentially relate to ischemic reperfusion in patients undergoing lobectomy, or alternatively may simply reflect the extent of manipulation, compression and contusion of lung tissue.

Aged↗

Systemic heparinization during peripheral vascular surgery: thromboelastographic, activated coagulation time, and heparin titration monitoring.

Fifteen patients (9 male, 6 female) undergoing peripheral vascular surgery were monitored during surgery for evidence of subclinical anticoagulation using the activated coagulation time (ACT), thromboelastography (TEG), and heparin titration monitoring. Assessments were made at 30-minute intervals before and after the occlusion clamp. Mean (+/- SD) ACT values preoperatively were 111 (17) seconds, and 10 minutes after 5,000 IU of heparin, the ACT was 264 (57) seconds (P < 0.001). Intraoperatively, there was a significant decline in ACT values at 30 minutes (ACT 228 [50] sec, P < 0.005) and 60 minutes (200 [46] sec, P < 0.001) postheparin. No significant difference in ACT was observed between samples drawn distally and proximally to the clamp. TEG profiles were abolished in all patients immediately following heparinization. However, in 2 patients nearly complete return of the TEG coagulation profile was observed prior to the termination of the procedure and was associated with ACT values less than 160 seconds. The heparin device was unable to accurately monitor heparin elimination at these low doses. Variability of patient response to heparinization necessitates the use of intraoperative monitoring of anticoagulation during peripheral vascular surgery.

Aged↗

201Tl myocardial perfusion SPET: adenosine alone or combined with dynamic exercise.

201Tl myocardial perfusion single photon emission tomography (SPET) with pharmacological coronary vasodilatation using adenosine is now often used in the investigation of a patient with ischaemic heart disease (IHD). In this study, we present data from two groups of patients. Group A (n = 40) experienced 201Tl SPET with adenosine only as the pharmacological stress test, using an infusion rate of 140 micrograms kg-1 min-1. Group B patients (n = 50) had the same test combined with low-level dynamic exercise. The side effects were noted for both groups and 201Tl SPET studies were acquired for stress and redistribution images. There was a lesser degree of non-cardiac side effects in patients of group B. There was a significant difference in the haemodynamic parameters between the two groups. There was no significant difference in overall sensitivity (87% versus 90%) and specificity (84% versus 88%) in the detection of IHD between the two groups. In conclusion, addition of low-level dynamic exercise with adenosine is to be preferred to adenosine infusion alone, as this protocol is better tolerated and may enhance the detection of right coronary artery disease (sensitivity = 82% versus 90%, n.s.).

Adenosine↗

Mechanism of action of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and an eIF-2 kinase (dsI).

Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.

Aminopeptidases↗

Cloning and characterization of complementary DNA encoding the eukaryotic initiation factor 2-associated 67-kDa protein (p67).

The eukaryotic initiation factor 2 (eIF-2)-associated 67-kDa glycoprotein (p67) protects eIF-2 alpha-subunit from inhibitory phosphorylation by eIF-2 kinases, such as heme-regulated inhibitor and double-stranded RNA-activated inhibitor. This promotes protein synthesis in the presence of eIF-2 kinases present in animal cells (Ray, M. K., Datta, B., Chakraborty, A., Chattopadhyay, A., Meza-Keuthen, S., and Gupta, N. K. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 539-543). In this study, the primary structure of rat p67 is determined by cDNA cloning. Based on the partial amino acid sequences of overlapping tryptic and cyanogen bromide cleaved fragments, degenerate oligonucleotides were synthesized and used as primers for the polymerase chain reaction to amplify the corresponding p67 cDNA fragment from rat liver first strand cDNA. The amplified DNA was then used as a probe to screen a rat tumor hepatoma (KRC-7) cDNA library, and a positive clone covering the entire coding region was obtained. From the cDNA sequence, an open reading frame that encodes p67 as a 480-amino acid protein with a molecular mass of 53 kilodaltons was predicted for the unglycosylated protein. The cloned cDNA was further characterized by in vitro transcription-coupled translation in micrococcal nuclease-treated reticulocyte lysate. The translated product migrated similarly to p67 in SDS-polyacrylamide gel electrophoresis and was precipitated with antibodies against p67. Northern blot analysis of rat liver poly(A)+ RNA showed a single size class (approximately 2 kilobases) of mRNA. The deduced amino acid sequence of the protein showed a highly charged N-terminal region composed of two basic polylysine blocks and an acidic aspartic acid block. The protein also exhibits significant sequence identity in the N-terminal region with human eIF-2 beta-subunit.

Amino Acid Sequence↗

Purification and analysis of a human sarcoma associated antigen.

S1, a heterophile antigen present on human sarcoma cell lines in culture, has been previously defined by this laboratory [1,2]. This antigen is also present in guinea-pig kidney. Purification of the antigen to homogeneity has now been achieved by a combination of ammonium sulfate fractionation, DEAE-cellulose, sephadex, high pressure liquid chromotography and affinity chromotography. S1 is a monomeric protein of 70,000 Da, as indicated by the presence of a single band on SDS-PAGE. Amino acid analysis demonstrates the prevalence of glycine, lysine and glutamic acid. Aspartic acid was found to be the N-terminal residue with further sequence of glycine-valine-alanine-glutamic acid (gly-val-ala-glut).

Amino Acids↗

Bovine internal mammary artery as a conduit for coronary revascularization: long-term results.

Graft patency after coronary artery bypass grafting depends largely on the choice of conduit. Because an increasing number of patients have insufficient or poor-quality autologous material, there is a need for a suitable synthetic graft that is readily available and easy to handle and that has good long-term patency. Early results suggest that the bovine internal mammary artery graft may meet these criteria. We have used a total of 26 such grafts in 18 patients. Postoperative angiography has been performed in 19 grafts in 14 patients, 3 to 23 months after operation; of these grafts, 3 are currently patent (15.8%, compared with 85.7% and 75.0% patency for native internal mammary artery and saphenous vein grafts in the same patients). We report the results of clotting studies and an analysis of lipid status. These patients do not, however, appear to represent any atypical group, either in terms of coagulopathy, native coronary artery size, or the type of vessel disease. Nevertheless, our poor results contrast markedly with the early enthusiasm reported from other centers.

Aged↗

Long-term results in the elderly following pulmonary resection for non-small cell lung carcinoma.

The long-term results of 647 patients undergoing pulmonary resection for non-small cell lung carcinoma (NSCLC) between 1980-1988 were reviewed. One hundred forty-five (22%) were elderly patients (70 years or more, group 1), with a mean age of 72.3 years (70-81) and the other 502 (18%) were younger (69 years or less, group 2) with a mean age of 61.4 (40-69) years. The male to female ratio was 4:1 in group 1 and 3:1 in group 2. The number of patients in group 2 (n = 234, 47%) who underwent pneumonectomy was significantly greater (P < 0.01), compared to group 1 (n = 47, 32%). Cardiopulmonary complications were more frequently observed in group 1 (19.3%) than in group 2 (7.4%), P < 0.05. Although cardiac complications (i.e. arrhythmias) were more common in the elderly group, pulmonary complications (retained secretions, atelectasis) occurred more commonly in the younger group. The overall hospital mortality in group 1 and group 2 was 8.9% and 5.3%, respectively (NS), and mortality following pneumonectomy in group 1 (10.6%) was similar to that of group 2 (7.6%) (NS). The 2- and 5-year overall actuarial survival rates were 61% and 30% in group 1 and 57% and 37% in group 2 (NS). Superior survival was achieved in patients in stage I of the disease in both groups. Cell type was not a determinant of long-term survival differences between the groups whereas type of operation (lobectomy) and sex (female) were.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Orbital granulocytic sarcomas (myeloid sarcomas) in acute nonlymphocytic leukemia.

In a series of 89 patients with acute leukemia, orbital granulocytic sarcomas were observed in 7. All these patients had acute nonlymphocytic leukemia, and they were all children. The orbital involvement usually was bilateral, and the patients had proptosis, conjunctival hemorrhage, and chemosis. Morphologic, cytochemical, and immunophenotypic analyses did not show a predilection for any particular myeloid cell type. Two patients had biphenotypic leukemias with myeloid components. The ocular manifestations responded well to chemotherapy irrespective of the hematologic response.

Adolescent↗

The eukaryotic initiation factor 2-associated 67-kDa polypeptide (p67) plays a critical role in regulation of protein synthesis initiation in animal cells.

The eukaryotic initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p67) isolated from reticulocyte lysate protects the eIF-2 alpha subunit from eIF-2 kinase-catalyzed phosphorylation and promotes protein synthesis in the presence of active eIF-2 kinases. We have now studied the roles of p67 and eIF-2 kinases in regulation of protein synthesis using several animal cell lysates and an animal cell line (KRC-7) in culture under various growth conditions. The results are as follows. (i) Both p67 and eIF-2 kinase(s) are present in active forms in all animal cells under normal growth conditions and p67 protects the eIF-2 alpha subunit from eIF-2 kinase-catalyzed phosphorylation, thus promoting protein synthesis in the presence of active eIF-2 kinases. (ii) In heme-deficient reticulocyte lysates and in serum-starved KRC-7 cells in culture, p67 is deglycosylated and subsequently degraded. This leads to eIF-2 kinase-catalyzed eIF-2 alpha-subunit phosphorylation and thus to protein synthesis inhibition. (iii) Addition of a mitogen (namely, phorbol 12-myristate 13-acetate) to serum-starved KRC-7 cells in culture induces an increase of p67 and thus increases protein synthesis. These results suggest the following conclusions. (i) Protein synthesis inhibition in a heme-deficient reticulocyte lysate is not due to the activation of an eIF-2 kinase (heme-regulated inhibitor), as is generally believed, but is due to degradation of p67. The heme-regulated inhibitor is present in an active form and possibly in equal amounts in both heme-deficient and heme-supplemented reticulocyte lysates but cannot phosphorylate eIF-2 alpha subunit because of the presence of p67. (ii) p67 is essential for protein synthesis as it protects the eIF-2 alpha subunit from eIF-2 kinase-catalyzed phosphorylation and promotes protein synthesis in the presence of one or more active eIF-2 kinases present in all animal cells. (iii) p67 is both degradable and inducible. Only the p67 level correlates directly with the protein synthesis activity of the cell, indicating that p67 is a critical factor in protein synthesis regulation in animal cells.

Animals↗

Fatal Legionella maceachernii pneumonia in Canada.

A case of pneumonia and acute tubular necrosis was caused by an initially unknown species of Legionella. The organism was later identified as Legionella maceachernii by a combination of cultural, biochemical, and serological methods along with a gas-liquid chromatographic profile.

Canada↗

Heparin rebound phenomenon--much ado about nothing?

Significant postoperative bleeding following open-heart surgery is often ascribed to the so-called heparin 'rebound' phenomenon and as such is treated with additional empiric doses of protamine sulphate. However, inappropriate protamine administration has been reported to be associated with acute pulmonary hypertension. The efficacy of heparin reversal was investigated in 42 patients undergoing open-heart surgery. The standard heparin bolus of 3 mg/kg body weight (4.1 IU/ml blood) administered before cardiopulmonary bypass was countered at the end of bypass using an empirical equivalent (3 mg/kg) of protamine. This regimen resulted in complete heparin neutralization (measured by the Hepcon HMS [Hemotec Inc., Englewood, CO, USA]) 15 min after protamine administration in all 42 patients, but heparin levels (0.4 IU/ml) were transiently detectable (duration less than 1 h) in six (14%) of the 42 cases 2 h later. Twenty-four hour postoperative bleeding in these patients did not differ significantly from that seen in patients who did not exhibit heparin rebound. Similarly, the thrombelastographic profiles (at 15 min and 2 h post-operation) and coagulation screen (prothrombin time, activated partial thromboplastin time, activated clotting time and platelets) did not differ significantly from those of non-rebound patients. The significance, if any, of the phenomenon of heparin rebound following cardiac surgery remains to be elucidated, and, until such time, conservative administration of protamine in response to 'rebound' is recommended.

Adolescent↗

Contact thermal burns of the cornea.

The records of 59 patients (66 eyes) with contact thermal burns of the cornea (unilateral in 52 cases and bilateral in 7) were reviewed to determine the causes, clinical presentation, management and complications of such injuries. Most of the injuries (90%) occurred at home. The commonest cause was splashing of boiling fluids (42% of cases), followed by contact with red-hot firecracker particles (18%) and lit match heads (17%). In 59 eyes (89%) the burn was limited to the corneal epithelium, in 5 (8%) the superficial stroma was also involved, and in 2 (3%) there was associated corneal perforation caused by mechanical impact of foreign bodies. Débridement of the coagulated epithelium with patching was the most successful treatment, healing 48 (73%) of the eyes. Postburn complications were rare, the most common being development of inferior symblepharon, in three eyes (4%).

Adolescent↗

Lack of late skin necrosis in man after high-dose irradiation using small field sizes: experiences of grid therapy.

Out of a total of 437 patients with superior vena caval syndrome or advanced malignancy, given single-dose grid radiotherapy, four survived to 7 years. The dose to the skin under each of the 77 holes in the grid was approximately 58 Gy. The lack of skin necrosis in the total of 308 skin circles of 1 cm diameter among these survivors, compared with known necrosis rates in larger irradiated areas, implies that there is a marked field-size effect for late necrosis in small areas of irradiated skin.

Adult↗