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Biomedical subjects

S C Lee

Publications and source records attributed to S C Lee.

At least 109 records · Page 6Linked to original sources
PubMed2001

Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene.

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Aged↗
PubMed2001

Young children's use of syntactic cues to learn proper names and count nouns.

In 6 experiments, 144 toddlers were tested in groups ranging in mean age from 20 to 37 months. In all experiments, children learned a novel label for a doll or a stuffed animal. The label was modeled syntactically as either a count noun (e.g., "This is a ZAV") or a proper name (e.g., "This is ZAV"). The object was then moved to a new location in front of the child, and a second identical-looking object was placed nearby. The children's task was to choose 1 of the 2 objects as a referent for the novel word. By 24 months, both girls (Experiment 2) and boys (Experiment 5) were significantly more likely to select the labeled object if they heard a proper name than if they heard a count noun. At 20 months, neither girls (Experiments 1 and 6) nor boys (Experiment 1) demonstrated this effect. By their 2nd birthdays, children can use syntactic information to distinguish appropriately between labels for individual objects and those for object categories.

Child Language↗
PubMed2001

A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus.

In systemic lupus erythematosus, antibodies against double-stranded DNA are a major contributor to renal disease. We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA. This sequence is also present in the extracellular domain of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a and NR2b. Here we show that the NR2 receptor is recognized by both murine and human anti-DNA antibodies. Moreover, anti-DNA antibodies with this cross-reactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus erythematosus contains these antibodies and also mediates neuronal death via an apoptotic pathway. These observations indicate that lupus antibodies cross-react with DNA and NMDA receptors, gain access to cerebrospinal fluid and may mediate non-thrombotic and non-vasculitic abnormalities of the central nervous system.

Animals↗
PubMed2001

Phage display mutagenesis of the chimeric dual cytokine receptor agonist myelopoietin.

Myelopoietins comprise a class of chimeric cytokine receptor agonists consisting of an hIL-3 (human interleukin-3) receptor agonist and an hG-CSF (human granulocyte colony-stimulating factor) receptor agonist linked head-to-tail at their respective carboxy and amino termini. The combination of an early acting cytokine (hIL-3) with a late acting one (hG-CSF) allows efficient hematopoeitic reconstruction following myeloablative insult, and drives differentiation of non-myelocytic lineages (ie thrombocytic lineages) that are inaccessible using hG-CSF alone, in both preclinical models and clinical settings. A myelopoietin species was displayed and mutagenized on filamentous bacteriophage: both component agonists of myelopoietin were presented in biologically functional conformations as each recognized its corresponding receptor. Five amino acid positions in a short region of the hG-CSF receptor agonist module of myelopoietin that had been identified as important for proliferative activity were mutagenized. Display was used because it allows very 'deep' mutagenesis at selected residues: >10(5) substitution variants were affinity-screened using the hG-CSF receptor and 130 new, active variants of myelopoietin were identified and characterized. None of the selected variants were significantly more active than the parental myelopoietin species in a hG-CSF-dependent cell proliferation assay, though many were as active. Many of these relatively high-activity variants contained parental amino acids at several positions, suggesting the parental sequence may already be optimal at these positions for the assays used, and potentially accounting for the failure to identify enhanced bioactivity variants. Analysis of substitutions of high-activity variants complements and extends previous alanine scanning, and other genetic and biochemical data for hG-CSF variants.

Cytokines↗
PubMed2001

A case of porphyria cutanea tarda in association with idiopathic myelofibrosis and CREST syndrome.

We report a 56-year-old Korean woman with porphyria cutanea tarda (PCT), showing multiple scarring bullae and hypertrichosis on sun-exposed areas of skin with postinflammatory hyperpigmentation. Sclerodermoid changes were also found on both hands, the face and neck. The patient had suffered from CREST syndrome, manifesting with Raynaud's phenomenon and sclerodactyly, for more than 15 years. Anticentromere antibody was positive. She had presented with splenomegaly 3 years before the development of PCT, and was diagnosed as having idiopathic myelofibrosis, based on bone marrow biopsy. In summary, she had had CREST syndrome for 15 years and later developed idiopathic myelofibrosis and PCT. This is the first reported case of PCT in association with idiopathic myelofibrosis and CREST syndrome.

CREST Syndrome↗
PubMed2001

The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: evidence for associations with type 2 diabetes and cholesterol levels.

BACKGROUND AND OBJECTIVES: There has been evidence that the S20G mutation in the islet amyloid polypeptide (amylin) gene may be associated with type 2 diabetes. In the present study, we investigated the distribution of the mutation in Hong Kong Chinese, and examined whether there was evidence for associations between the mutation and type 2 diabetes and/or metabolic profiles. SUBJECTS AND METHODS: This study involved 227 early and 235 late-onset (defined as onset age < or = 40 and > 40 years, respectively) type 2 diabetic patients, as well as 126 nondiabetic subjects. The mutation was detected using a PCR-RFLP method. RESULTS: We identified six (2.6%) and one (0.4%) patients heterozygous for the mutation from the early and late-onset groups, respectively (P = 0.05). None of the nondiabetic subjects had the mutation. Insulin deficiency and poor glycaemic control were not common findings amongst carriers of the mutation. In the early onset group, the patients with the mutation had lower plasma levels of total (4.3 +/- 0.9 mmol/l vs. 5.3 +/- 1.1 mmol/l, P = 0.02) and low density lipoprotein (LDL)-cholesterol (2.3 +/- 0.7 mmol/l vs. 3.2 +/- 0.9 mmol/l, P = 0.01) than those without the mutation. CONCLUSIONS: Our data suggest that the islet amyloid polypeptide gene mutation might be associated with early occurrence of type 2 diabetes and lower plasma levels of total and low density lipoprotein-cholesterol in the Chinese population.

Adolescent↗
PubMed2001

Catecholamines in hyperpnoea-induced airway constriction of guinea pigs.

1. We found previously that propranolol augments hyperpnoea-induced bronchoconstriction (HIB). This study was performed to investigate the underlying mechanism of this aug- menting action of propranolol. 2. In the first series, 45 young Hartley guinea-pigs were divided into five groups: control; propranolol; adrenalectomy; metoprolol and reserpine. Each animal underwent three periods: baseline, hyperpnoea, and recovery. For each animal 1 ml of arterial blood was sampled during the baseline and recovery periods. 3. Treatments of propranolol, metoprolol, and reserpine caused significant decreases in both dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV0.1) during the baseline period. Hyperpnoea caused slight but not significant decreases in Crs, FEV0.1, and maximal expiratory flow at 50% total lung capacity (TLC) (V(max50)) during the recovery period in the control group. Propranolol, but not other treatments, significantly augmented these decreases (indicating HIB). Plasma noradrenaline and adrenaline levels in the reserpine group were not detectable. The above treatments or hyperpnoea did not induce any significant effect on the plasma noradrenaline level. Plasma adrenaline level of the control group was higher than that of either adrenalectomy or reserpine group during the baseline and the recovery periods. 4. In the second series, we avoided repeated blood samplings. Forty-eight animals were evenly divided into two groups: control and propranolol. Each group was again evenly divided into three subgroups: baseline; hyperpnoea, and recovery. Five minutes into the recovery period, we demonstrated HIB in the control group. In terms of V(max50), this HIB was significantly augmented by propranolol. Plasma noradrenaline and adrenaline levels, however, were not significantly altered by either hyperpnoea or propranolol. 5. Taken together, these data suggest that propranolol-augmented HIB has no direct relationship with decreased catecholamine activity.

Adrenalectomy↗
PubMed2001

Effect of mouth washing on the.

BACKGROUND: Mouth washing is often mentioned as a possible method to eliminate the interference of urease activity in the oral cavity before the [13C]-urea breath test (UBT). However, the effectiveness of mouth washing prior to testing has not been demonstrated clearly in the literature. Thus, the present study was designed to examine the consistency of the [13C]-UBT and the effects of mouth washing on it. METHODS: A total of 101 healthy volunteers underwent the [13C]-UBT three times. The first and second tests used a standard protocol and collected samples at 5, 10, 15 and 30 min. In the third test, the procedure was the same except that mouth washing was omitted. RESULTS: We used 5 permil (/1000) as the cut-off value and there were 21 (20.8%) positive cases. The kappa values for the samples collected at 5, 10, 15 and 30 min between the first and second tests were 0.68, 0.97, 1 and 1, respectively, and all showed good consistency, except for the sample collected at 5 min. Judging from the mean value of the [13C] enrichment of the first and second tests (with mouth washing) and the third test (without mouth washing), 50 (63.3%), 15 (18.8%), 0 and 0 cases at 5, 10, 15 and 30 min, respectively, changed from negative to positive. There were 14 (17.5%) and six (7.5%) cases at 15 and 30 min, respectively, whose [13C] enrichment changed from less than 3 (negative) to between 3 and 5 (border zone). CONCLUSIONS: These results indicate that mouth washing had an important effect on samples obtained at 5 and 10 min, while this influence decreased at 15 min and was lowest at 30 min.

Adult↗
PubMed2001

Lipoblastoma.

BACKGROUND/PURPOSE: Lipoblastoma is a rare benign mesenchymal tumor of embryonal fat that occurs almost exclusively in infants and children. This study was done to determine the clinical and pathologic characteristics of lipoblastoma. METHODS: Nine cases of pathologically proven lipoblastoma from 1979 to 1997 were reviewed. There were 6 boys and 3 girls ranging in age from 3 months to 29 months. RESULTS: A soft tissue mass was the chief complaint in 7 patients, abdominal distension in 1 patient with a retroperitoneal mass, and defecation difficulty in 1 patient with a perirectal mass. In 4 patients, tumors occurred on the back. Other tumor location includes the neck, scrotum, retroperitoneum, perirectal area, and buttock in 1 patient each. Lesions measured 2.3 to 19.5 cm. Complete excision was done in 8 patients. One perirectal tumor was removed by both the posterior sagittal approach and the intraabdominal approach but incompletely resected. Two tumors located on the back recurred with intraspinal extension 12 months and 18 months after resection. Second resection and second resection with laminectomy were done. Leg pain and urinary incontinence developed in 1 patient but improved on conservative treatment. CONCLUSIONS: Lipoblastoma is a benign neoplasm but can frequently recur (25%) in spite of complete excision. Lipoblastomas occurring on the back had a high recurrence rate (50%) and associated with intraspinal extension. J Pediatr Surg 36:905-907.

Child, Preschool↗
PubMed2001

Inhibition effect of new farnesol derivatives on all-trans-retinoic acid metabolism.

All-trans-retinoic acid (atRA) is a promising anticancer and antiwrinkle drug. However, its clinical application is limited because it is rapidly metabolized by the induced cytochrome P450 (P450). In this study, farnesol derivatives are proposed as new inhibitors to prevent P450-mediated metabolism. The farnesol derivatives were suc-farnesol and mal-farnesol, which were synthesized by the chemical conjugation of farnesol with succinic anhydride and maleic anhydride, respectively. The inhibition effects of farnesol, farnesoic acid, and farnesol derivatives on the atRA metabolism were evaluated in microsome and in AMC-HN-6 cells. In the microsome experiment, suc-farnesol and mal-farnesol strongly inhibited atRA metabolism at 10(minus;4) mol/L concentration by as much as 61% and 77%, respectively. In the cell experiment, the inhibition effects of farnesol derivatives on the atRA metabolism showed similar tendency as the results in the microsome experiment, even if the effect was somewhat decreased. Effects of farnesoic acid and farnesol, however, were not significant. This research suggests that carboxylic end groups, such as atRA and hydrophobicity, might be important factors causing the higher inhibition effect, and that derivatization of farnesol can be 1 method to develop new inhibitors of atRA metabolism.

Antimetabolites↗
PubMed2001

Quantitative analysis of normal major salivary glands using computed tomography.

OBJECTIVES: We sought to calculate the size and the computed tomography (CT) number of normal parotid and submandibular glands and to evaluate their relationship with respect to sex, age, and obesity in the Korean population. STUDY DESIGN: The authors investigated the axial CT images of 42 healthy volunteers. The maximum cross-sectional area (MCSA) was used as an indicator of the size of the gland. Three regions of interest on axial scans were selected to calculate the mean CT number. RESULTS: There was a significant decrease in the mean MCSA of the submandibular gland and the CT number of both glands with age. The MCSA of the submandibular gland in males was larger than that in females. There was a close correlation between the parotid and the submandibular glands with respect to the CT number, as well as between the left and right glands with respect to the MCSA and the CT number. The body mass index was positively correlated with the MCSA of the parotid gland, whereas the body mass indexes and the CT numbers of both glands were negatively correlated. CONCLUSIONS: Both age and obesity are closely correlated with the size and the CT number of the major salivary glands. Moreover, the correlation between the CT numbers of the parotid and the submandibular glands may be used for diagnostic purposes.

Adult↗
PubMed2001

Association of retinopathy with a microsatellite at 5' end of the aldose reductase gene in Chinese patients with late-onset Type 2 diabetes.

Recent experimental data suggest that a microsatellite polymorphism at 5' end of the aldose reductase gene may be associated with the development of diabetic retinopathy. In the present study, we examined the allele distribution of the polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at diagnosis > or =35 years) Type 2 diabetes, but no clinical evidence of cataract. Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy were older (52 +/- 11 years vs. 60 +/- 9 years, p < 0.01) and had a higher HbA1c (8.9 +/- 2.2% vs. 7.7 +/- 2.0%, p < 0.01 with adjustment for age) than those without the complication. Amongst all of the patients, we detected 10 microsatellite alleles and found that allele Z-4 was overpresented in those with retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for more than 80% of the overall frequency, between the two groups of patients. Using multiple logistic regression analysis (R2 = 0.17, p < 0.01), we found that age (p < 0.01) and HbA1c (p < 0.05) were associated with retinopathy. In conclusion, our data suggest that the occurrence of diabetic retinopathy in the Chinese population may be influenced by clinical and metabolic factors. The aldose reductase gene may be implicated, but is not likely to play a major role.

Adult↗
PubMed2001

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) interacts with dengue virus core protein.

Heterogeneous nuclear ribonucleoprotein K (hnRNP K), a component of hnRNP particles, is involved in several steps of gene expression regulation. Dengue (DEN) virus, a member of the Flaviviridae, is the primary cause of illnesses such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In mature DEN virus particles, the core protein is a structural protein that forms a nucleocapsid complex with genomic RNA. Very little of its biologic functions is known. Here, using an in vitro binding assay and coimmunoprecipitation analysis, we report a protein-protein interaction between the DEN virus core protein and hnRNP K. The C-terminal hydrophilic region of the DEN virus core protein, spanning amino acid residues 73 to 100, is required for such interaction. Results of glutathione-S transferase binding assays indicated that the core protein-hnRNP K interaction might be abolished in the presence of hnRNP K cognate nucleic acids. Furthermore, in a cotransfection experiment, the repressive effect of hnRNP K on C/EBPbeta-mediated transcription activation could be reversed by full-length DEN virus core protein but not by a truncated form containing amino acids 1-72. Our results suggest that, on DEN virus infection, the multiple functions of cellular hnRNP K may be affected by the virus core protein.

Amino Acid Sequence↗
PubMed2001

Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocortical tumors.

Our previous study showed that the mutation hotspots of the K-ras proto-oncogene in human functional adrenocortical tumors are in codons 15, 16, 18, and 31, thus differing from the sites in other tumors. In addition, analyzing the K-Ras protein by a recombinant DNA technique showed that the activity of endogenic GTPase and the GTPase-activating protein (GAP)-binding ability were significantly decreased in patients with these tumors. The aim of this study was to understand whether those K-ras mutants, which were found only in human adrenocortical tumors, play an important role in these tumors. Thus, the mutant K-ras cDNA was constructed with mammalian expression vectors and transfected into normal adrenocortical cells. The amount of cortisol secreted by the transfected cells was 20 to 30 times that of normal cells. Furthermore, Northern blot analysis revealed that the expression of the three steroidogenesis-related genes P450(scc) (cholesterol side-chain cleavage enzyme), P450(C17) (17alpha-hydroxylase/17, 20-lyase), and P450(C21) (steroid 21-hydroxylase) gene increased in the transfected cells. The K-ras oncogene significantly increases cortisol secretion by normal adrenocortical cells.

Adrenal Cortex↗
PubMed2001

Natural radionuclides contents and radon exhalation rates in building materials used in South Korea.

The natural radionuclide (226Ra, 232Th and 40K) contents of building materials commonly used in South Korea have been determined by a gamma ray spectroscopy system using a high purity germanium detector. The radon exhalation rates and emanation coefficients of building materials have also been studied. The average concentrations of 226Ra, 232Th and 40K in building materials were in the range of 6.47-271 Bq.kg-1, N.D.-89.9 Bq.kg-1 and 16.8-1081 Bq.kg-1, respectively. The average radon exhalation rates and emanation coefficients were in the range of 0.0061-0.2404 Bq.kg-1.h-1 and 2.39-11.5%, respectively.

Construction Materials↗