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Biomedical subjects

M C Lee

Publications and source records attributed to M C Lee.

At least 37 records · Page 2Linked to original sources
PubMed2003

Developmental hemispheric asymmetry of interregional metabolic correlation of the auditory cortex in deaf subjects.

The functional connectivity of the auditory cortex might be altered in deaf subjects due to the loss of auditory input. We studied the developmental changes of functional connectivity of the primary auditory cortex (A1) in deaf children, deaf adults, and normal hearing adults by examining interregional metabolic correlation with (18)F-FDG PET. The mean activity of FDG uptake in the cytoarchitectonically defined A1 region served as a covariate in the interregional and interhemispheric correlation analysis. A1 metabolic rate was correlated with that of the ipsilateral superior temporal lobe in both normal and deaf subjects. This correlated area was larger in deaf children than in deaf or normal hearing adults. Concerning the functional connectivity of A1, a hemispheric asymmetry was found in that the extent of interregional correlation was clearly larger in the right than in the left hemisphere. This asymmetry was particularly pronounced in the younger deaf children. Both extent and asymmetry of the functional connectivity of A1 subsided with age. Contrary to this, a correlation between the left and the right primary auditory cortices was absent in younger deaf children but became apparent as they grew older.

Adolescent↗
PubMed2003

The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes.

OBJECTIVE: To investigate the in vitro effects of dehydroepiandrosterone (DHEA) on human osteoarthritic chondrocytes. DESIGN: Chondrocytes isolated from human osteoarthritic knee cartilage were three-dimensionally cultured in alginate beads, except for cell proliferation experiment. Cells were treated with DHEA in the presence or absence of IL-1beta. The effects on chondrocytes were analyzed using a 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay (for chondrocyte proliferation), a dimethylmethylene blue (DMB) assay (for glycosaminoglycan (GAG) synthesis), and an indole assay (for DNA amount). Gene expressions of type I and II collagen, metalloproteinase-1 and -3 (MMP-1 and -3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as the IL-1beta-induced gene expressions of MMP-1 and -3 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein synthesis of MMP-1 and -3 and TIMP-1 was determined by Western blotting. RESULTS: The treatment of chondrocytes with DHEA did not affect chondrocyte proliferation or GAG synthesis up to 100 micro M of concentration. The gene expression of type II collagen increased in a dose-dependent manner, while that of type I decreased. DHEA suppressed the expression of MMP-1 significantly at concentrations exceeding 50 micro M. The gene expression of MMP-3 was also suppressed, but this was without statistical significance. The expression of TIMP-1 was significantly increased by DHEA at concentrations exceeding 10 micro M. The effects of DHEA on the gene expressions of MMP-1 and -3 were more prominent in the presence of IL-1beta, in which DHEA suppressed not only MMP-1, but also MMP-3 at the lower concentrations, 10 and 50 micro M, respectively. Western blotting results were in agreement with RT-PCR, which indicates that DHEA acts at the gene transcription level. CONCLUSIONS: Our study demonstrates that DHEA has no toxic effect on chondrocytes up to 100 micro M of concentration and has an ability to modulate the imbalance between MMPs and TIMP-1 during OA at the transcription level, which suggest that it has a protective role against articular cartilage loss.

Adjuvants, Immunologic↗
PubMed2003

Brain glucose metabolic changes associated with neuropsychological improvements after 4 months of treatment in patients with obsessive-compulsive disorder.

OBJECTIVE: The study was designed to elucidate regional brain metabolic changes according to a treatment and their relationship with neuropsychological performance changes in obsessive-compulsive disorder (OCD). METHOD: Cerebral glucose metabolic rates were repeatedly measured before and after treatment in 10 patients with OCD using [18F]-2-fluoro-deoxyglucose positron emission tomography (PET). They were compared on a voxel-basis, and the correlations were counted between the regional metabolic changes and the degree to improvement on the neuropsychological assessments. RESULTS: After treatment, the patients showed significant (P < 0.005, two-tailed) regional metabolic changes in multiple brain areas involving frontal-subcortical circuits and parietal-cerebellar networks. Especially, the metabolic changes of the putamen, the cerebellum, and the hippocampus were significantly correlated with the improvement of the immediate- and delayed-recall scores of the Rey-Osterrieth Complex Figure Test (RCFT). CONCLUSION: These results suggest a possibility that metabolic changes of frontal-subcortical and parietal-cerebellar circuit changes may underlie cognitive improvements in patients with OCD.

Adult↗
PubMed2002

In vitro release of vancomycin from vancomycin-loaded blood coated demineralised bone.

In vitro and in vivo studies have demonstrated the possibility that cancellous bone could be used as a carrier of antibiotics for local delivery. However, the release of antibiotics from the loaded cancellous bone is too rapid and uncertain. We hypothesised that demineralisation of cancellous bone would increase the amount of antibiotic adsorbed, and coating of the freeze-dried antibiotic-impregnated cancellous bone with bio-compatible material would prolong antibiotic release. Bovine cancellous bone blocks of equal size were demineralised using a 0.5 N HCl solution and loaded with vancomycin solution under vacuum. The loaded bone blocks were then freeze-dried. To obtain a bio-compatible coating, the vancomycin-impregnated bone blocks were soaked in fresh human venous blood for 3 h. The release of impregnated antibiotic from the bone blocks was evaluated in phosphate-buffered saline and foetal bovine serum. It was found that significantly larger amounts of vancomycin were adsorbed into the demineralised bone blocks than into the un-demineralised blocks. The blood coating was found to increase the duration of vancomycin release from the blocks. With demineralisation and blood coating, the blocks eluted vancomycin higher than therapeutic concentration for a 5-week period.

Absorption↗
PubMed2002

A Monte Carlo dose calculation tool for radiotherapy treatment planning.

A Monte Carlo user code, MCDOSE, has been developed for radiotherapy treatment planning (RTP) dose calculations. MCDOSE is designed as a dose calculation module suitable for adaptation to host RTP systems. MCDOSE can be used for both conventional photon/electron beam calculation and intensity modulated radiotherapy (IMRT) treatment planning. MCDOSE uses a multiple-source model to reconstruct the treatment beam phase space. Based on Monte Carlo simulated or measured beam data acquired during commissioning, source-model parameters are adjusted through an automated procedure. Beam modifiers such as jaws, physical and dynamic wedges, compensators, blocks, electron cut-outs and bolus are simulated by MCDOSE together with a 3D rectilinear patient geometry model built from CT data. Dose distributions calculated using MCDOSE agreed well with those calculated by the EGS4/DOSXYZ code using different beam set-ups and beam modifiers. Heterogeneity correction factors for layered-lung or layered-bone phantoms as calculated by both codes were consistent with measured data to within 1%. The effect of energy cut-offs for particle transport was investigated. Variance reduction techniques were implemented in MCDOSE to achieve a speedup factor of 10-30 compared to DOSXYZ.

Computer Simulation↗
PubMed2002

Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation.

OBJECTIVE: This study was designed to investigate whether an elevated serum antithyroglobulin antibody (TgAb) reflects cancer recurrence in thyroglobulin (Tg)-undetectable patients with differentiated thyroid carcinoma (DTC) after thyroid ablation. DESIGN: We measured serum TgAb level and evaluated the disease status in 226 DTC patients who had undergone remnant ablation and showed an undetectable Tg result as assessed by immunoradiometric assay. MEASUREMENTS: Radioligand assay of TgAb was performed. Recurrence was assessed by 131I scan, 18F-fluorodeoxyglucose positron emission tomography, sonography, computed tomography, or by surgical operation. RESULTS: Fifty-one patients (22.6%) of the Tg-undetectable patients showed positive TgAb, and 25 (49.0%) of these were confirmed with recurrence. The recurrence rate of TgAb-positive patients was higher than that of TgAb-negative patients (3.4%; P < 0.0001). During follow-up, 73.1% of the disease-free patients showed spontaneously decreased TgAb levels. A total of 71.4% of patients with recurrent cancer, who showed responses to surgical operation or radio-iodine treatment, also showed a decreased TgAb level. CONCLUSIONS: Persistently elevated TgAb levels appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum Tg results. Thus, the routine measurement of TgAb in such patient populations may be indicated.

Adolescent↗
PubMed2002

Synthesis of 188 Re-labelled long chain alkyl diaminedithiol for therapy of liver cancer.

Radioisotope-labelled lipiodol has been used in the therapy of liver cancer. Recently a lipiodol solution of 188Re-labelled diaminedithiol (DD) has been reported to show a high uptake in the liver cancer. We synthesized long-chain alkyl DD derivatives to improve their uptake and retention in tissue. As the length of the alkyl chain increased, tissue uptake and retention also increased due to hydrophobic interaction with lipiodol. Among the synthesized compounds, the lipiodol solution of 188Re-HDD, the DD derivative with the longest side chain (C16), is a promising agent for therapy of liver cancer.

Animals↗
PubMed2002

Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer.

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.

Adult↗
PubMed2001

Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception.

Opioid receptors are known to undergo complex regulatory changes in response to ligand exposure. In the present study, we examined the effect of morphine on the in vitro and in vivo density and trafficking of delta opioid receptors (deltaORs). Prolonged exposure (48 hr) of cortical neurons in culture to morphine (10 microm) resulted in a robust increase in the internalization of Fluo-deltorphin, a highly selective fluorescent deltaOR agonist. This effect was mu-mediated because it was entirely blocked by the selective mu opioid receptor antagonist d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) and was reproduced using the selective mu agonist fentanyl citrate. Immunogold electron microscopy revealed a marked increase in the cell surface density of deltaORs in neurons exposed to morphine, indicating that the increase in Fluo-deltorphin internalization was caused by increased receptor availability. Prolonged morphine exposure had no effect on deltaOR protein levels, as assessed by immunocytochemistry and Western blotting, suggesting that the increase in bioavailable deltaORs was caused by recruitment of reserve receptors from intracellular stores and not from receptor neosynthesis. Complementary in vivo studies demonstrated that chronic treatment of adult rats with morphine (5-15 mg/kg, s.c., every 12 hr) similarly augmented targeting of deltaORs to neuronal plasma membranes in the dorsal horn of the spinal cord. Furthermore, this treatment markedly potentiated intrathecal d-[Ala(2)]deltorphin II-induced antinociception. Taken together, these results demonstrate that prolonged stimulation of neurons with morphine markedly increases recruitment of intracellular deltaORs to the cell surface, both in vitro and in vivo. We propose that this type of receptor subtype cross-mobilization may widen the transduction repertoire of G-protein-coupled receptors and offer new therapeutic strategies.

Analgesics↗
PubMed2001

Ganglioside composition and histology of a spontaneous metastatic brain tumour in the VM mouse.

Glycosphingolipid abnormalities have long been implicated in tumour malignancy and metastasis. Gangliosides are a family of sialic acid-containing glycosphingolipids that modulate cell-cell and cell-matrix interactions. Histology and ganglioside composition were examined in a natural brain tumour of the VM mouse strain. The tumour is distinguished from other metastatic tumour models because it arose spontaneously and metastasizes to several organs including brain and spinal cord after subcutaneous inoculation of tumour tissue in the flank. By electron microscopy, the tumour consisted of cells (15 to 20 microm in diameter) that had slightly indented nuclei and scant cytoplasm. The presence of smooth membranes with an absence of junctional complexes was a characteristic ultrastructural feature. No positive immunostaining was found for glial or neuronal markers. The total ganglioside sialic acid content of the subcutaneously grown tumour was low (12.6 +/- 0.9 microg per 100 mg dry wt, n = 6 separate tumours) and about 70% of this was in the form of N-glycolylneuraminic acid. In contrast, the ganglioside content of the cultured VM tumour cells was high (248.4 +/- 4.4 microg, n = 3) and consisted almost exclusively of N-acetylneuraminic acid. The ganglioside pattern of the tumour grown subcutaneously was complex, while GM3, GM2, GM1, and GD1a were the major gangliosides in the cultured tumour cells. This tumour will be a useful natural model for evaluating the role of gangliosides and other glycolipids in tumour cell invasion and metastasis.

Animals↗
PubMed2001

Endothelin receptors in human and guinea-pig gallbladder muscle.

We measured contraction of muscle strips caused by endothelin (ET) isopeptides and binding of (125)I-ET-1 to muscle cell membranes prepared from human and guinea-pig gallbladders. Visualization of (125)I-ET-1 binding sites in tissue was performed by autoradiography. Results in human were similar to those in guinea-pig. ET-1 caused tetrodotoxin and atropine-insensitive contraction. The relative potencies for ET isopeptides to cause contraction were ET-1=ET-2>ET-3. ET-1 caused contraction was only slightly inhibited by BQ-123 (potent ET(A) receptor antagonist) and not by BQ-788 (potent ET(B) receptor antagonist). It was inhibited by the combination of both. Autoradiography localized (125)I-ET-1 binding to the smooth muscle layer. Binding of (125)I-ET-1 to muscle cell membranes was saturable and specific. Analysis of dose-inhibition curves demonstrated the presence of two classes of receptors. One class (ET(A) receptor) had a high affinity for ET-1 and ET-2 but a low affinity for ET-3, and the other (ET(B) receptor) a high affinity for ET-1, ET-2 and ET-3. These results demonstrate that similar to guinea-pig, human gallbladder possesses both ET(A) and ET(B) receptors cooperating to mediate muscle contraction.

Adult↗
PubMed2001

The solution structure of C1-T1, a two-domain proteinase inhibitor derived from a circular precursor protein from Nicotiana alata.

A two-domain portion of the proteinase inhibitor precursor from Nicotiana alata (NaProPI) has been expressed and its structure determined by NMR spectroscopy. NaProPI contains six almost identical 53 amino acid repeats that fold into six highly similar domains; however, the sequence repeats do not coincide with the structural domains. Five of the structural domains comprise the C-terminal portion of one repeat and the N-terminal portion of the next. The sixth domain contains the C-terminal portion of the sixth repeat and the N-terminal portion of the first repeat. Disulphide bonds link these C and N-terminal fragments to generate the clasped-bracelet fold of NaProPI. The three-dimensional structure of NaProPI is not known, but it is conceivable that adjacent domains in NaProPI interact to generate the circular "bracelet" with the N and C termini in close enough proximity to facilitate formation of the disulphide bonds that form the "clasp". The expressed protein, examined in the current study, comprises residues 25-135 of NaProPI and encompasses the first two contiguous structural domains, namely the chymotrypsin inhibitor C1 and the trypsin inhibitor T1, joined by a five-residue linker, and is referred to as C1-T1. The tertiary structure of each domain in C1-T1 is identical to that found in the isolated inhibitors. However, no nuclear Overhauser effect contacts are observed between the two domains and the five-residue linker adopts an extended conformation. The absence of interactions between the domains indicates that adjacent domains do not specifically interact to drive the circularisation of NaProPI. These results are in agreement with recent data which describe similar PI precursors from other members of the Solanaceae having two, three, or four repeats. The lack of strong interdomain association is likely to be important for the function of individual inhibitors by ensuring that there is no masking of reactive sites upon release from the precursor.

Amino Acid Sequence↗
PubMed2001

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Adult↗
PubMed2001

Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression.

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) seems to play an important role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF expression. We investigated the effect of VEGF expression on renal cell carcinoma (RCC) and the correlation between the expression of VEGF and tumor angiogenesis and p53 protein expression. METHODS: Sixty-two RCCs were examined by immunohistochemical studies with anti-VEGF, anti-p53, and anti-CD34 antibodies. RESULTS: Forty tumors (80.6%) were classified as VEGF positive, and 28 tumors (45.2%) were positive for p53 protein. The microvessel density was 75.3 +/- 33.5. A significant correlation was found between VEGF expression and both the nuclear grade (P < 0.05) and the TNM stage (P < 0.05). The tumors with VEGF expression had a significantly higher microvessel density than those without VEGF expression (P < 0.01). There was no statistically significant correlation between p53 protein and VEGF expression. No statistically significant differences in survival were found to be associated with microvessel density, VEGF expression or p53 protein expression. By using multivariate survival analyses, nuclear grade (P < 0.05) and TNM stage (P < 0.05) were the only independent prognostic factors. CONCLUSIONS: Our data do not show a direct regulation of VEGF expression by p53. We suggest that VEGF expression plays a role in the promotion of angiogenesis in RCC.

Adult↗
PubMed2001

Antioxidant effect of melatonin in human retinal neuron cultures.

This study investigates whether the neurohormone melatonin can prevent the retinal neuronal injury caused by reactive oxygen species (ROS) in cultured human retinal neuronal cells. Cultures of human retinal neuronal cells established from a variety of donors were grown to 14 days and then subjected to experimental hypoxanthine/xanthine oxidase (HX/XO)-induced injury. Intracellular production of ROS by administration of HX/XO was confirmed by flow cytometry; the ROS resulted in both apoptotic and necrotic pattern of cell death in the retinal neuron cultures. The efficacy of melatonin against ROS injury was quantitated by MTT assay, enzyme immunoassay, and immunocytochemistry for neurofilament protein. The antioxidative effect of melatonin was compared with that of alpha-tocopherol. Retinal neuronal injury significantly reduced in a dose-response manner by a treatment of 1.0-8.0 mM alpha-tocopherol. Melatonin, in concentrations of more than 2.0 mM, also significantly reduced the injury. About 70% of cells are rescued by pretreatment with 1.0 mM alpha-tocopherol and 8.0 mM melatonin in the MTT assay. Our observations suggest that melatonin can rescue retinal neurons from ROS injury in human retinal cell cultures.

Adult↗
PubMed2001

Quantification of F-18 FDG PET images in temporal lobe epilepsy patients using probabilistic brain atlas.

A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). It is a good frame for calculating volume of interest (VOI) in many fields of brain images. After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices (AI) were calculated and used for finding epileptogenic zones in mesial temporal lobe epilepsy (mTLE). FDG PET images from 18 surgically confirmed mTLE patients and 22 age-matched controls were spatially normalized to the average brain MRI template of ICBM. Counts from normalized PET images were multiplied with the probability of 12 VOIs from SPAM images in both temporal lobes. Finally AI were calculated on each pair of VOIs, and compared with visual assessment. If AI of mTLE patients were not within 2.9 standard deviation from those of normal control group (P < 0.008; Bonferroni correction for P < 0.05), epileptogenic zones were considered to be found successfully. The counts of VOIs in the normal control group were symmetric (AI < 4.3%, paired t test P > 0.05) except for those of the inferior temporal gyrus (P < 0.001). By AIs in six pairs of VOIs, PET in mTLE had deficit on one side (P < 0.05). Lateralization was correct in only 14/18 of patients by AI, but 17/18 were consistent with visual inspection. In three patients with normal AI, PET images were symmetric on visual inspection. The asymmetric indices obtained by taking the product of the statistical probability anatomical map and FDG PET, correlated well with visual assessment in mTLE patients. SPAM is useful for the quantification of VOIs in functional images.

Adult↗
PubMed2001

Bombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes.

Bombycis corpus(BC) or Bombyx Batryticatus, a batryticated silkworm and white-stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In the present study, we have examined the protective effect of the water extracts against Amyloid- beta(A beta) 25-35 peptide-induced cytotoxicity by microscopic observation and LDH assay, and its action on antioxidative enzymes using cultured astrocyte cells. A beta 25-35-induced cell death was protected by the application of water extract of BC in a dose-dependent manner, and concentrations of 10(-6)to 10(-7)g ml(-1)showed a significant effect compared to exposure of A beta 25-35 alone. When antioxidative enzyme activities such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S transferase (GST) were assayed after A beta 25-35 treatment, most enzyme activities were decreased in a similar fashion. BC treatment of A beta 25-35-treated astrocytes did not affect the enzyme activities of catalase, GSH-Px and GST. However, only SOD activity was enhanced by BC treatment and this may result from the potentiation of the antioxidative ability of BC. The protective effect of BC against cytotoxicity induced by Abeta 25-35 strongly indicates that BC could be a protective agent for free radical generating compounds, and that Abeta 25-35 is not only a potent lipid peroxide inducer, but can also cause changes in antioxidative enzymes. From the results, it was concluded that BC has a protective effect against Abeta -induced cytotoxicity in cultured astrocyte cells through the inhibition of lipid peroxidation and protection of antioxidative enzymes.

Amyloid beta-Peptides↗