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Biomedical subjects

A Tan

Publications and source records attributed to A Tan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Introduction of oxygen into the alkyl chain of N-decyl-dNM decreases lipophilicity and results in increased retention of glucose residues on N-linked oligosaccharides.

N-Alkylation of the alpha-glucosidase inhibitor 1-deoxynojirimycin (dNM) dramatically increases its inhibitory potency (Tan et al., J. Biol. Chem., 266, 14504-14510, 1991). However, the possibility of extending the alkyl chain to N-decyl-dNM is limited by an increase of detergent-like (amphiphilic) properties of long-chain alkylated dNM derivatives. Substitution of methylene groups in the N-decyl chain by oxygen reduced the amphiphilicity of N-decyl-dNM derivatives, while retaining their superior inhibitory properties. In intact HepG2 cells, the compound N-7-oxadecyl-dNM was found to result in the most pronounced retention of glucose residues on N-linked glycans. Permeabilization of the plasma membrane with the bacterial toxin Streptolysin O improves the inhibitory properties of the derivatives N-3,6,9-trioxadecyl-, N-7,10,13-trioxatetradecyl-, N-3-oxadecyl- and N-7-oxadecyl-dNM, but not those of dNM. These observations suggest differences in the mode of entry of the oxygen-substituted dNM derivatives in comparison with dNM. We observed that the dNM derivative N-3,6,9-trioxadecyl-dNM, devoid of inhibitory activity in intact cells, was inhibitory in Streptolysin O-permeabilized cells. Thus, the permeability barriers posed by plasma membrane and endoplasmic reticulum membrane are not equivalent. The use of a permeabilized cell system thus allows the elaboration of inhibitory principles for novel bioactive compounds where study of the isolated enzymes may not be possible, and where intact cells are not a suitable target due to permeability barriers.

1-Deoxynojirimycin↗
PubMed1994

GATA-1 is expressed in acute erythroblastic leukaemia.

Previous studies have demonstrated the expression of GATA-1 (a DNA-binding nuclear protein) in erythrocytes, megakaryocytes, eosinophils, basophils, mast cells, early marrow progenitor cells and in mouse and human erythroid leukaemia cell lines. We studied 31 bone marrow specimens from patients with acute myeloid leukaemia (AML) for GATA-1 expression by reverse transcriptase/polymerase chain reaction (RT/PCR) analysis. GATA-1 expression was detected in all of the patients with erythroleukaemia, and in one of nine patients with megakaryoblastic leukaemia, but absent from 17 patients with French-American-British (FAB) M1-5 leukaemia. In AML, GATA-1 expression is indicative of differentiation to the erythroid and possibly megakaryocytic lineages, analogous to its expression in normal haemopoiesis.

Bone Marrow↗
PubMed1994

Bone marrow transplantation in Malaysia.

The sole BMT centre in Malaysia caters only for children. Since 1987, 89 transplants have been performed using reverse barrier nursing techniques. The overall survival rate is 73% with the majority of survivors leading normal lives. The early and late infection rates of 46% and 13%, respectively, are comparable to those of other centres. Although the early septicaemia rate is 36% the immediate mortality rate is < 10%. GVHD is less frequent and severe and the interstitial pneumonitis rate lower than that in the West. The average cost of US $8000 per transplant is much lower than the cost of a transplant performed overseas. Thus we believe that our paediatric BMT programme is simple and cost-effective.

Adolescent↗
PubMed1994

Acute outcome of percutaneous Inoue-balloon mitral commissurotomy.

This study examines the acute results and the potential impact, if any, of 16 clinical, echocardiographic, hemodynamic and balloon-related variables on the acute outcomes of Inoue-balloon percutaneous transvenous mitral commissurotomy (PTMC). Of 107 patients, PTMC was successfully completed in 105 (98%) without cardioembolism or death, and resulted in an increase in mitral valve area from 0.8 +/- 0.2 cm2 to 1.7 +/- 0.4 cm2 (p = 0.0001) as assessed echocardiographically. Optimal results defined as a valve area improvement of > or = 50% and/or a final valve area of > or = 1.5 cm2 without significant mitral regurgitation (> or = 2 grade increase in mitral regurgitation or a final regurgitation > or = 3+) was obtained in 96 patients (91%). Significant mitral regurgitation was observed in six patients. On univariate analysis, patients with suboptimal results were older (52 +/- 7 vs. 44 +/- 10 years, p = 0.037) and were likely to have the procedure performed during the learning phase (first 33 vs.. subsequent 72 patients, p = 0.007) than those with optimal results, and patients with resultant significant mitral regurgitation had more severe pre-existing mitral regurgitation compared with those without (1.4 +/- 0.5 vs. 0.7 +/- 0.7, p = 0.0098). However, there were no independent predictors of either acute outcome identified in multivariate analysis. We therefore conclude that although Inoue-balloon PTMC is a safe and highly effective procedure with a low risk of creating severe mitral regurgitation, the acute outcomes cannot be accurately predicted.

Adult↗
PubMed1994

Radiofrequency catheter ablation of accessory pathways: the initial experience in Singapore.

Radiofrequency catheter ablation is a recently introduced non-surgical technique for curing patients with arrhythmias as a result of conduction over an accessory pathway in patients with the Wolff-Parkinson-White (WPW) syndrome. We present our initial experience with this technique. There were 90 patients (61 males, 29 females) with a mean age of 37 +/- 14.4 years (range: 13-73 years). All except one were symptomatic with a mean duration of symptoms of 10 +/- 9.4 years (range: 0.1-40 years). The indications for catheter ablation were failure of drug therapy in 71, patient's preference in 10, increased risk of sudden death in 6 and almost incessant tachycardia in 3. The radiofrequency ablation was performed using a deflectable 7 French 4 mm tip electrode catheter positioned at the mitral or tricuspid annulus. The site of the accessory pathway was localised by electrophysiological study and radiofrequency energy applied via the tip of the catheter. There were 100 accessory pathways as 10 (10%) patients had multiple accessory pathways. There were 69 (69%) left free wall, 11 (11%) posteroseptal, 13 (13%) right free wall, 6 (6%) right anteroseptal accessory pathways and one (1%) midseptal accessory pathways. Ninety-six percent (96%) of the accessory pathways were successfully ablated on the first ablation. Two of the 4 initially unsuccessful ablations were successfully reablated, giving an overall success rate of 98%. There were no major complications. In conclusion, radiofrequency catheter ablation of accessory pathways is highly successful and safe and provides a definitive cure for patients with the WPW syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Involvement of the vacuolar H(+)-ATPases in the secretory pathway of HepG2 cells.

The macrolide antibiotic concanamycin B is a highly selective inhibitor (IC50 = 5 nM) of the H(+)-ATPases of the vacuolar system. We have examined the effects of concanamycin B on the constitutive secretory pathway of the human hepatoma cell line, HepG2. In cells exposed to 10 nM concanamycin B, transport from the endoplasmic reticulum to the Golgi occurs at normal rates, as determined by pulse-chase analysis of endoglycosidase H-sensitive product in conjunction with subcellular fractionation experiments. However, intra-Golgi trafficking or Golgi to plasma membrane delivery is significantly impaired. A delay in the onset of secretion of the major secretory proteins, albumin, alpha 1-antitrypsin and transferrin is observed. Processing of N-linked glycans by sialyltransferases is inhibited, resulting in secreted glycoproteins which are modified less extensively. In view of the acidic pH of the trans-Golgi and the trans-Golgi network, these studies suggest that acidification by vacuolar ATPases is critical to achieving timely secretion and correct N-linked glycan modifications of proteins which follow the constitutive secretory pathway.

Albumins↗
PubMed1993

Early ambulation following diagnostic 7-French cardiac catheterization: a prospective randomized trial.

There is a paucity of randomized studies concerning transfemoral cardiac catheterization and its complications, in particular that of 7F catheterization. Accordingly, we conducted a prospective, randomized trial comparing early ambulation (group A) 6 hr after diagnostic 7F cardiac catheterization versus late ambulation (group B) the following morning. A total of 273 patients were randomized in the study; 142 in group A and 131 in group B (NS). Except for a difference in the indications for catheterization, the baseline and procedure-related parameters were similar between the 2 groups. Early hematoma (formed within 6 hr) developed in 6 (4%) and 7 (5%) patients in groups A and B, respectively (NS). Similarly, there was no difference in the incidence of late hematoma formation (2% in each group). All hematomas detected were small and required no surgical intervention or extension of hospital stay. Our data showed that early ambulation following 7F left heart catheterization is feasible and safe. The access site complication rate is acceptably low and minor in nature.

Cardiac Catheterization↗
PubMed1993

Laser iridoplasty in the treatment of severe acute angle closure glaucoma.

Twenty eyes of 19 patients presenting with acute angle closure glaucoma (AACG) which failed to respond to medical treatment were treated with laser iridoplasty. In all 20 eyes, laser peripheral iridectomy (PI) was prevented by a hazy cornea. In all cases, iridoplasty resulted in a rapid and significant reduction in intraocular pressure. Laser iridoplasty appears to have a useful role in the management of medically unresponsive AACG, particularly in those cases where laser peripheral iridotomy (PI) has failed or is not possible to perform.

Acute Disease↗
PubMed1993

New directions in cardiovascular mapping and therapy.

Cardiovascular mapping has allowed us to fully understand the mechanisms of some of the cardiac arrhythmias and enabled us to devise new therapeutic options for them. Endocardial mapping by electrophysiological studies using three to four endocardial catheters introduced via the vein or artery to the heart allows us to directly map the electrical activity of the heart during sinus rhythm and during abnormal tachyarrhythmias. The simultaneous recording of electrical activity from the surface electrocardiogram, right ventricular apex, His bundle, high right atrium, coronary sinus, with or without a roving mapping catheter, enables us to precisely map the electrical activation sequence in the heart. This technique has been especially useful for mapping supraventricular tachycardias and the precise mapping of the accessory pathway or slow pathway potentials have now allowed us to selectively ablate them using radiofrequency energy delivered via the tip of the endocardial catheter. Intraoperative direct cardiac mapping has allowed us to reconfirm the findings of endocardial catheter mapping immediately prior to surgery. The intraoperative mapping is more precise and allows direct visualisation of the abnormal site for the surgeon to operate. Computerised mapping using multichannel recordings has facilitated mapping of the abnormal site for patients with haemodynamically unstable or nonsustained ventricular tachycardia, and thus allows the surgeon to perform surgical resection or cryoablation of the abnormal site. Cardiovascular mapping has thus enabled us not only to understand the mechanisms of cardiac arrhythmias but allows us to provide curative therapy for patients who are at risk from sudden arrhythmic death or otherwise need life long drug therapy.

Adult↗
PubMed1992

Retrograde transport from the Golgi region to the endoplasmic reticulum is sensitive to GTP gamma S.

The involvement of GTP-binding proteins in the intracellular transport of the secretory glycoprotein alpha 1-antitrypsin was investigated in streptolysin O-permeabilized HepG2 cells. This permeabilization procedure allows ready access to the intracellular milieu of the membrane-impermeant, nonhydrolyzable GTP analog GTP gamma S. In streptolysin O-permeabilized HepG2 cells, the constitutive secretory pathway remains functional and is sensitive to GTP gamma S. Exposure of HepG2 cells to brefeldin A resulted in redistribution of Golgi-resident glycosyltransferases (including both alpha 2----3 and alpha 2----6 sialyltransferases) to the ER. This redistribution was sensitive to GTP gamma S. Our results suggest that GTP-binding proteins are involved in the regulation not only of the anterograde, but also of the retrograde, pathway.

Bacterial Proteins↗
PubMed1992

Non-surgical closure of patent ductus arteriosus with the Rashkind PDA occluder system.

Transcatheter closure of Patent Ductus Arteriosus (PDA) was done in 18 children using the USCI Rashkind PDA occluder system. Patient age ranged from 1.2 to 14 years and their weights ranged from 8 to 36 kg. Isolated restrictive PDA was present in 15 patients; 3 had additional cardiac defects. The diameter of the PDA ranged from 2 to 6 mm as determined by lateral aortogram. PDA occlusion was successfully done in all 18 children. Ten 12 mm and eight 17 mm occluders were implanted with no complications. Post-implant aortogram showed complete ductal closure in 6 and trivial or small residual ductal flow in 12 cases. Doppler color flow mapping done within 3 days of the procedure showed complete ductal closure in 9, 8 had trivial ductal flow and 1 had small ductal flow. Transcatheter technique using a Rashkind PDA occluder system is a safe and effective method of non-surgical PDA occlusion.

Adolescent↗
PubMed1992

Percutaneous transluminal coronary angioplasty in acute cardiogenic shock: an overview of the current strategy with a case illustration.

Cardiogenic shock from severe left ventricular dysfunction remains the most common cause of death in patients with acute myocardial infarction despite the advent of inotropic agents and intra-aortic balloon support. Lytic agents have not convincingly reduced mortality when administered in a shock scenario. Recently, observational studies have demonstrated survival benefit when mechanical revascularisation, particularly balloon angioplasty, is performed early in such patients. In this article, we report a case of an extensive anterior myocardial infarction with cardiogenic shock who underwent successful acute balloon angioplasty and prolonged intracoronary thrombolysis and use it to illustrate the current evolving interventional approach in the treatment of such a complex clinical syndrome.

Acute Disease↗
PubMed1992

Diurnal tear cycle: evidence for a nocturnal inflammatory constitutive tear fluid.

To investigate the tear film in the closed eye, microliter tear samples were collected without overt reflex stimulation throughout the diurnal cycle, with closed eye samples recovered immediately upon eye opening. Samples were subjected to agarose, polyacrylamide, and two-dimensional electrophoresis, coupled with immunofixation, immunoblot, and lectin blot assays. Major protein constituents were densitometrically and immunologically quantified. Results revealed a distinct progression in composition from reflex to open to closed eye tear samples. Total protein increased from 6.0 to 9.0 to 18.0 mg/ml, secretory IgA increased from less than 0.23 to 0.85 to 8.40 mg/ml, and serum albumin increased from 0.02 to 0.06 to 1.10 mg/ml. In contrast, concentrations of the major reflex tear components (lysozyme, lactoferrin, and tear specific prealbumin) remained essentially static. Immunoblot assay for complement C3 and C3c revealed that eye closure was associated with C3 activation. Results indicate that: (1) the reflex and closed eye tear layers represent opposite extremes in composition and likely origins, with open eye tear film suggesting an intermediate origin; (2) reflex tears are derived from a neurologically inducible lacrimal or accessory gland secretion composed almost exclusively of lysozyme, lactoferrin, tear specific prealbumin, and a minor mixed alpha to beta globulin fraction; (3) upon eye closure, reflex secretion ceases or greatly diminishes, with ongoing slower flow maintained by a constitutive secretion composed almost exclusively of secretory IgA; (4) the closed eye environment induces a subclinical inflammation, accounting in part for the marked rise in albumin concentration. This increase, coupled with that of secretory IgA, may play a critical role in protecting the closed eye environment from pathogens. However, this may render the closed eye environment particularly vulnerable to inflammatory and immune-mediated pathological processes, such as those seen with extended wear soft contact lenses.

Adult↗
PubMed1991

Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships.

The ability of the glucosidase inhibitor 1-deoxynojirimycin (dNM) and a series of N-alkylated dNM derivatives to interfere with biosynthesis, transport, and maturation of the glycoprotein alpha 1-antitrypsin in HepG2 cells was investigated. Inhibition of endoplasmic reticulum glucosidase I and II by dNM and its derivatives resulted in an intracellular accumulation of alpha 1-antitrypsin with glucose-containing high mannose type oligosaccharides (precursor). N-alkylation of dNM increased its potency in inhibiting endoplasmic reticulum glucosidases, as determined from the concentration required for half maximal inhibition. N-Alkylated derivatives of dNM were better able to inhibit glucosidase I than glucosidase II (deduced from the number of glucose residues retained in Endo H-releasable oligosaccharides). The inhibition of glucosidase activity imposed by alkylated dNM derivatives was less easily reversed than that by dNM, an effect most pronounced for N-methyl-dNM. Branching of the alkyl group of dNM derivatives decreased the inhibitory potency. Although dNM and its derivatives interfered strongly with intracellular oligosaccharide processing, they did not completely block N-glycan maturation of alpha 1-antitrypsin even at the highest concentrations tested.

1-Deoxynojirimycin↗
PubMed1991

The ligand recognized by ELAM-1 on HL60 cells is not carried by N-linked oligosaccharides.

The sialyl Lewis-x determinant is a ligand for ELAM-1, a major adhesion molecule for HL60 cells and neutrophils. ELAM-1 expression can selectively be induced on human umbilical vein endothelial cells (HUVEC) by tumor necrosis factor, interleukin 1 and lipopolysaccharide. The determinant sialyl Lewis-x is found on both glycolipids as well as on glycoproteins. Using specific inhibitors of the biosynthesis of N-linked glycosylated glycoproteins, we investigated whether N-linked glycans or their modifications are involved in ELAM-1-dependent adhesion of HL60 cells to activated HUVEC. The inhibitors of glycoprotein processing N-methyl-deoxynojirimycin, 1-deoxymannojirimycin and swainsonine did not affect ELAM-1-dependent adhesion. Complex-type N-linked glycans are not required for ELAM-1 mediated adhesion, and therefore the ligand for ELAM-1 is most likely a glycolipid, or a glycoprotein carrying O-linked oligosaccharides.

Cell Adhesion↗