Search PubMed⌕ Search

Biomedical subjects

S T Lim

Publications and source records attributed to S T Lim.

At least 37 records · Page 2Linked to original sources

Focal pulmonary uptake during Tc-99m myocardial perfusion SPECT imaging.

PURPOSE: To evaluate the incidence and origin of abnormal focal pulmonary uptake during myocardial perfusion SPECT imaging (MSPECT). METHODS: For evaluation of chest pain, 790 men and 581 women (mean age, 56 +/- 13 years) underwent MSPECT. All of them received adenosine for pharmacologic stress and Tc-99m tetrofosmin (TF, n = 817) or Tc-99m sestamibi (MIBI, n = 554) for myocardial perfusion imaging. RESULTS: Review of chest radiography with or without computed tomography revealed 111 (8.1%) focal pulmonary diseases. Among them, 38 (34.2%) showed focal pulmonary uptake (TF, 22; MIBI, 16); 27 (30.7%) of 88 showed previous pulmonary tuberculosis; 2 of 10 (20%) benign pulmonary nodules; 4 of 5 (80%) metastatic lung cancers; 2 of 4 (50%) primary lung cancers; and 3 of 4 (75%) pneumonias. No difference in uptake was noted for the two imaging agents. Intensity of uptake did not vary with origin of the uptake. Focal abnormal pulmonary uptake was found in 2.8% of patients undergoing MSPECT and in 34.2% of patients in whom radiological examinations showed regional pulmonary disease. In patients with abnormal pulmonary uptake on MSPECT, 16% had a malignant lesion, whereas 75% of patients with a pulmonary nodule shown on radiography and focal pulmonary uptake on MSPECT had a malignant lesion. CONCLUSIONS: Although the incidence of abnormal pulmonary uptake during MSPECT was very low, the incidence of malignant lesions in the patients with nodular pulmonary uptake was relatively high.

Adenosine↗

The C-terminal tail of the metabotropic glutamate receptor subtype 7 is necessary but not sufficient for cell surface delivery and polarized targeting in neurons and epithelia.

Complex neuronal functions rely upon the precise sorting, targeting, and restriction of receptors to specific synaptic microdomains. Little is known, however, of the molecular signals responsible for mediating these selective distributions. Here we report that metabotropic glutamate receptor subtype 7a (mGluR7a) is polarized at the basolateral surface when expressed in Madin-Darby canine kidney (MDCK) epithelial cells but is not polarized when expressed in cultured hippocampal neurons. Truncation of the mGluR7 cytoplasmic tail produces a protein that is restricted to a perinuclear intracellular compartment in both neurons and MDCK cells, where this protein colocalizes with a trans-Golgi network antigen. The mGluR7 cytoplasmic domain appended to the transmembrane portion of the vesicular stomatitis virus G protein and the ectodomain of human placental alkaline phosphatase is distributed over the entire cell surface in cultured neurons. When expressed in MDCK cells, this construct remains in an intracellular compartment distinct from endosomes or lysosomes. Thus, the cytoplasmic tail domain of mGluR7 is necessary but not sufficient for polarized targeting in MDCK monolayers, whereas in neurons the cytoplasmic tail is sufficient for cell surface expression but not polarization. Additional mechanisms are likely required to mediate mGluR7 neuronal polarization and synaptic clustering.

Animals↗

Structural characterization of beta-D-(1 --> 3, 1 --> 6)-linked glucans using NMR spectroscopy.

Nondestructive structural analysis of a series of beta-D-(1 --> 3, 1 --> 6)-linked glucans (laminaran, curdlan, yeast glucan, scleroglucan, etc.) was performed using two-dimensional NMR spectroscopy. The relative ratios of H-1 at different AGUs provided the information about DPn and DB. The alpha-, and beta-anomeric protons on reducing terminals were assigned at 5.02 to approximately 5.03 ppm (J 3.6 to approximately 3.7 Hz), and 4.42 to approximately 4.43 ppm (J 7.6 to approximately 7.9 Hz), respectively, whereas the H-1 protons of internal AGUs and beta-(1 --> 6)-branched AGUs appeared at 4.56 to approximately 4.59 ppm (J 7.6 to approximately 7.8 Hz), and 4.26 to approximately 4.28 ppm (J 7.6 to approximately 10.6 Hz), respectively, in a mixed solvent of 6:1 Me2SO-d6-D2O at 80 degrees C. In the solvent, the OH peaks were eliminated from the spectra allowing the H-1 protons to appear clearly. In addition, the nonreducing terminal H-1 and H-1 at the AGU next to reducing terminal could be assigned at 4.45 to approximately 4.46 ppm (J 7.8 to approximately 7.9 Hz), and 4.51 to approximately 4.53 ppm (J 7.8 Hz), respectively. The DPn of the laminaran was 33 (polydispersity 1.12) and the DB was 0.07. The number of glucosyl units in the side chain of laminaran is more than one. The DPn and DB of the water-insoluble yeast glucan were 228 and 0.003, respectively. However the DPn of water soluble yeast glucan phosphate and curdlan was changed upon the number of freeze-drying processes and the content of water in the mixed solvent, respectively. And the DB of those were calculated as 0.02 and 0, respectively. The DB of scleroglucan was precisely calculated as 0.33, compared with the previously reported data. The H-1s at different AGUs of the various beta-D-(1 --> 3, 1 --> 6)-linked glucans having different DB can be exactly assigned by their chemical shifts in the mixed solvent system. This NMR analysis can be effectively used to determine the DP and DB of polysaccharides in a simple and non-destructive manner.

Carbohydrate Conformation↗

Inhibitory effect of Artemisia asiatica alkaloids on acetylcholinesterase activity from rat PC12 cells.

We screened 42 Korean traditional tea plants to determine the inhibitory effect of acetylcholinesterase and attenuation of toxicity induced by amyloid-beta peptide, which were related to the treatment of Alzheimer's disease (AD). The methanolic extract from Artemisia asiatica among tested 42 tea plants, showed the highest inhibitory effect (48%) on acetylcholinesterase in vitro. The methanolic extract was further separated with n-hexane, chloroform, and ethyl acetate of water, in order. The chloroform solubles, which were high in inhibitory effect of acetylcholinesterase, were repeatedly subjected to open column chromatography on silica gel. From the highest inhibitory fraction (78%) on acetylcholinesterase, the single compound was obtained by the Sep-Pak Cartridge (C18: reverse phase column). This compound was found to react positively on Dragendorff's reagent (potassium bismuth iodide), which typically reacted with the alkaloid. This compound was purified by HPLC (mu-bondapack C18 reverse phase column: 3.9 x 150 mm). The IC50 (the concentration of 50% enzyme inhibition) value of this compound was 23 micrograms/ml and the inhibitory pattern on acetylcholinesterase was mixed with competitive/non-competitive type. We examined the effects of this compound on toxicity induced by A beta (25-35) in rat pheochromocytoma PC12 cells. Pretreatment of the PC12 cells for 2 h with an alkaloid of Artemisia asiatica (1200 microg/ml) reduced the toxicity induced by A beta. This study demonstrated that an alkaloid of Artemisia asiatica, which was metabolized to small molecule in digestive tract and then could pass through the blood-brain barrier, appeared to be an acetylcholinesterase inhibitor with a blocker of neurotoxicity induced by A beta in human brain causing Alzheimer's disease.

Acetylcholinesterase↗

Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan.

Rapid mucociliary clearance of intranasally administered drugs is often a key factor in determining the bioavailability of such therapeutic agents. The use of mucoadhesive microparticles provide a potential strategy for improving retention of drugs within the nasal cavity, and thereby improve the resultant pharmacokinetic profile. This study describes the comparison of a number of novel, potentially mucoadhesive microspheres, prepared by solvent evaporation, composed of hyaluronic acid (HA), chitosan glutamate (CH) and a combination of the two with microcapsules of HA and gelatin prepared by complex coacervation. The microspheres had a mean particle size of 19.91+/-1.57 microm (HA), 28.60+/-1.34 microm (HA/CH), 29.47+/-3.58 microm (CH). The incorporation of a model drug, gentamicin sulphate (%) was 46.90+/-0.53 (HA), 28.04+/-1.21 (HA/CH) and 13.32+/-1.04 (CH). The in vitro release profiles of microsphere formulations prepared by solvent evaporation were determined. The release of gentamicin from HA and HA/CH was 50% longer than CH and was best modelled as a release from a matrix. The degree of mucoadhesion of each formulation was investigated by determining the mucociliary transport rate (MTR) of the microparticles across an isolated frog palate. Acacia/gelatin microcapsules were used as a positive control. The rank order of mucoadhesion for the microspheres and the microparticles was HA=HA/CH>CH>HA/gelatin>CHins. The entrapment of gentamicin did not affect the mucoadhesive properties (P>0.05, Mann--Whitney U-test). The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential of HA with the penetration enhancing effect of chitosan.

Acacia↗

A novel targeting signal for proximal clustering of the Kv2.1 K+ channel in hippocampal neurons.

The discrete localization of ion channels is a critical determinant of neuronal excitability. We show here that the dendritic K+ channels Kv2.1 and Kv2.2 were differentially targeted in cultured hippocampal neurons. Kv2.1 was found in high-density clusters on the soma and proximal dendrites, while Kv2.2 was uniformly distributed throughout the soma and dendrites. Chimeras revealed a proximal restriction and clustering domain on the cytoplasmic tail of Kv2.1. Truncations and internal deletions revealed a 26-amino acid targeting signal within which four residues were critical for localization. This signal is not related to other known sequences for neuronal and epithelial membrane protein targeting and represents a novel cytoplasmic signal responsible for proximal restriction and clustering.

Amino Acid Sequence↗

The predictive value of uvulo-palatoglossal junctional ulcers as an early clinical sign of exanthem subitum due to human herpesvirus 6.

BACKGROUND: The clinical sign of uvulo-palatoglossal junctional (UPJ) ulcers was first noted in 1983 in a 5.5-month-old baby with exanthem subitum (ES). An earlier prospective clinical study showed that there was a strong association of UPJ ulcers and occurrence of ES with a positive predictive value of 95.3% and negative predictive value of 100%. OBJECTIVE: To determine the value of uvulo-palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem subitum (ES) due to human herpesvirus 6 (HHV 6) infection. STUDY DESIGN: A case-control study of 20 febrile children with UPJ ulcers versus 26 febrile children without UPJ ulcers. These children were followed up for any development of ES and investigated for human herpesvirus 6 (HHV 6) as the causative agents of the febrile episodes. RESULTS: In this study, 20 out of 46 febrile children aged 3 months to 3 years with UPJ ulcers were virologically and/or serologically confirmed to be due to primary HHV 6 infection. The rest of the 26 children without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers, only 17 of the 19 children with adequate follow-up till subsidence of fever developed ES. None of the 26 children without UPJ ulcers developed ES. CONCLUSION: Statistically, there was a significant association of UPJ ulcers as an early sign of ES with a positive predictive value of 89.5% and negative predictive value of 100%. This finding also suggests that the presence of UPJ ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6 infection.

Antibodies, Viral↗

Factors associated with male infertility: a case-control study of 218 infertile and 240 fertile men.

OBJECTIVE: To determine the likely risk factors, such as smoking and drinking habits, and occupational groups, for infertility in a group of infertile men with no known cause, compared with a group of fertile men; and to examine the effects of the semen parameters, such as volume, density, motility, viability and normal morphology, on fertility. DESIGN: A case-control study. SETTING: The department of obstetric and gynaecology of a tertiary general hospital. PARTICIPANTS: Six hundred and forty consecutive male partners of couples trying to conceive were recruited from an infertility clinic. Of these, the cases comprised 218 men who had no known cause for their infertility. Two hundred and forty men whose wives were pregnant at the time of the study were recruited as controls. RESULTS: The semen parameters (e.g. density, total sperm counts, motility, viability and normal morphology) of all cases were significantly poorer than that of the controls. The risk of infertility is associated with smoking (crude OR 2 x 82, 95% CI 1 x 93-4 x 13; adjusted OR 2 x 96; 95% CI 1 x 98-4 x 42). Technicians (adjusted OR 2 x 81; 95% CI 1 x 51-4 x 24) and professional, senior officials and managers were also at a greater risk of infertility (adjusted OR 2 x 36; 95% CI 1 x 26-4 x 40), compared with service and clerical workers. The significant factors predicting infertility were smoking, density of sperm, and viability of sperm. Smoking increased the odds of being infertile. Higher sperm counts and larger percentage of viable sperm decrease the odds of infertility. Based on the multiple logistic regression model, the odds ratio for infertility = (94 x 70) x (2 x 88(smoking)) X (0 x 29(logdensity)) X (0 x 95(viability)). CONCLUSION: Smoking, density of sperm and the viability of sperm are significant predictors for infertility among men.

Adult↗

Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization.

Using growth factors to induce vasculogenesis is a promising approach in the treatment of ischemic legs and myocardium. Because the vasculogenesis requires a cascade of growth factors, their receptors, and intracellular signals, such therapies may require the application of more than a single growth factor. We examined the effect of 2 endothelial cell-specific growth factors, angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), on primary cultured porcine coronary artery endothelial cells. VEGF, but not Ang1, increased DNA synthesis and cell number. Ang1 or VEGF induced migration and sprouting activity, increased plasmin and matrix metalloproteinase-2 secretion, and decreased tissue inhibitors of metalloproteinase type 2 secretion. A combination of the submaximal doses of Ang1 and VEGF enhanced these effects and was more potent than the maximal dose of either alone. In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone. Angiographic analyses revealed that larger blood vessels were formed after gene delivery of Ang1 or Ang1 plus VEGF than after VEGF gene delivery. These results suggest that combined treatment of Ang1 and VEGF could be used to produce therapeutic vascularization.

Angiopoietin-1↗