Search PubMed⌕ Search

Biomedical subjects

M K Lee

Publications and source records attributed to M K Lee.

At least 127 records · Page 7Linked to original sources
PubMed1999

Detection of RET/PTC oncogene rearrangements in Korean papillary thyroid carcinomas.

The prevalence of RET/PTC rearrangement in papillary thyroid carcinomas has been found to vary widely in different populations. Recent studies, however, have reported no significant geographical difference between Asian and Western countries. In addition, there are some disagreements about the correlation of RET/PTC expression with clinical aggressiveness. We have performed this study in order to examine the prevalence of RET/PTC-1, RET/PTC-2, and RET/PTC-3 rearrangements in Korean papillary thyroid carcinomas, and to ascertain its clinical relevance. Thyroid tumors from 31 patients histologically confirmed to be papillary carcinomas were included in this study. To find rearrangements, we utilized reverse transcription-polymerase chain reaction (RT-PCR) and automated direct sequencing. Initial and follow-up clinical data were obtained from the patients' medical records. We identified two tumors containing RET/PTC-1 (2/31, 6.5%) and two containing RET/PTC-2 (2/31, 6.5%). However, we could not find RET/PTC-3 rearrangement in any patients (0/31). In conclusion, we report RET/PTC rearrangements in 4 of 31, (12.9%) Korean patients with papillary thyroid carcinomas, a higher prevalence than previously reported in this population.

Adult↗
PubMed1999

Current concepts on lung development.

Recent molecular genetic and embryonic organ culture studies have implicated several novel regulatory processes in the coordination of lung development. Failure of pulmonary initiation results from interruptions of the sonic hedgehog/patched/Gli and Nkx 2.1 signaling pathways. Sonic hedgehog null mutants and Gli2/Gli3 compound null mutants each exhibited failed tracheoesophageal septation. However, proximodistal epithelial differentiation is disrupted by compound Gli mutation, but is preserved in sonic hedgehog mutants. Null mutation of Nkx 2.1 also abrogates tracheoesophageal septation in association with thyroid and pituitary agenesis. Primary tracheal branching is regulated by fibroblast growth factor-10 signaling; in the murine fibroblast growth factor-10 null phenotype, the lung fails to separate from the foregut and morphogenesis is arrested distal to the trachea. Several genes in the fibroblast growth factor-10 pathway have homologous roles in fruit fly tracheal organogenesis, and corresponding Drosophila mutations yield strikingly similar phenotypes. Recent data also indicate that airway branching can be regulated by vascular endothelial growth factor, suggesting mutual regulation of airway and vascular development. The bases of pulmonary left-right asymmetry and laterality have also been investigated. The transforming growth factor-beta superfamily members Lefty-1, Lefty-2, and nodal comprise a regulatory pathway whose function is required for the development of left-right asymmetry, whereas left-right laterality is dependent on regulation of dynein expression by the transcription factor hepatocyte nuclear factor-4. Terminal lung differentiation is modulated by yet another set of signals. Hoxa5 null mutants exhibit tracheal occlusion and surfactant protein deficiency, whereas fibroblast growth factor receptor-2 and -4 compound null phenotypes include abrogated neonatal alveolization, perturbed alveolar myofibroblast differentiation, and persistent neonatal elastin deposition. These new contributions represent substantial advances toward a comprehensive molecular model of pulmonary development.

Animals↗
PubMed1999

Microbial desulfurization of a crude oil middle-distillate fraction: analysis of the extent of sulfur removal and the effect of removal on remaining sulfur.

Rhodococcus sp. strain ECRD-1 was evaluated for its ability to desulfurize a 232 to 343 degrees C middle-distillate (diesel range) fraction of Oregon basin (OB) crude oil. OB oil was provided as the sole source of sulfur in batch cultures, and the extent of desulfurization and the chemical fate of the residual sulfur in the oil after treatment were determined. Gas chromatography (GC), flame ionization detection, and GC sulfur chemiluminesce detection analysis were used to qualitatively evaluate the effect of Rhodococcus sp. strain ECRD-1 treatment on the hydrocarbon and sulfur content of the oil, respectively. Total sulfur was determined by combustion of samples and measurement of released sulfur dioxide by infrared absorption. Up to 30% of the total sulfur in the middle distillate cut was removed, and compounds across the entire boiling range of the oil were affected. Sulfur K-edge X-ray absorption-edge spectroscopy was used to examine the chemical state of the sulfur remaining in the treated OB oil. Approximately equal amounts of thiophenic and sulfidic sulfur compounds were removed by ECRD-1 treatment, and over 50% of the sulfur remaining after treatment was in an oxidized form. The presence of partially oxidized sulfur compounds indicates that these compounds were en route to desulfurization. Overall, more than two-thirds of the sulfur had been removed or oxidized by the microbial treatment.

Biodegradation, Environmental↗
PubMed1999

Identification of residues in domain III of Bacillus thuringiensis Cry1Ac toxin that affect binding and toxicity.

Alanine substitution mutations in the Cry1Ac domain III region, from amino acid residues 503 to 525, were constructed to study the functional role of domain III in the toxicity and receptor binding of the protein to Lymantria dispar, Manduca sexta, and Heliothis virescens. Five sets of alanine block mutants were generated at the residues (503)SS(504), (506)NNI(508), (509)QNR(511), (522)ST(523), and (524)ST(525). Single alanine substitutions were made at the residues (509)Q, (510)N, (511)R, and (513)Y. All mutant proteins produced stable toxic fragments as judged by trypsin digestion, midgut enzyme digestion, and circular dichroism spectrum analysis. The mutations, (503)SS(504)-AA, (506)NNI(508)-AAA, (522)ST(523)-AA, (524)ST(525)-AA, and (510)N-A affected neither the protein's toxicity nor its binding to brush border membrane vesicles (BBMV) prepared from these insects. Toward L. dispar and M. sexta, the (509)QNR(511)-AAA, (509)Q-A, (511)R-A, and (513)Y-A mutant toxins showed 4- to 10-fold reductions in binding affinities to BBMV, with 2- to 3-fold reductions in toxicity. Toward H. virescens, the (509)QNR(511)-AAA, (509)Q-A, (511)R-A, and (513)Y-mutant toxins showed 8- to 22-fold reductions in binding affinities, but only (509)QNR(511)-AAA and (511)R-A mutant toxins reduced toxicity by approximately three to four times. In the present study, greater loss in binding affinity relative to toxicity has been observed. These data suggest that the residues (509)Q, (511)R, and (513)Y in domain III might be only involved in initial binding to the receptor and that the initial binding step becomes rate limiting only when it is reduced more than fivefold.

Animals↗
PubMed1999

Fas is expressed in murine pancreatic islet cells and an insulinoma cell line but does not mediate their apoptosis in vitro.

CD4+ lymphocytes are the most important effector cells in autoimmune diabetes of NOD mice, although some role of CD8+ T cells has been demonstrated. However, it is unknown how CD4+ lymphocytes are able to destroy pancreatic beta-cells that do not express MHC (major histocompatibility complex) class II molecules. Apoptotic cell death mediated by an interaction of Fas with Fas ligand (FasL) could be a mechanism by which MHC class II-negative pancreatic beta-cells are destroyed by CD4+ T lymphocytes. We have examined the expression of Fas molecules in pancreatic islet cells, as well as in a NOD-derived mouse insulinoma cell line (MIN6N8). In addition, the role of Fas-mediated apoptosis in pancreatic islet cell death was explored in vitro. Although Fas expression was not detected by flow cytometric analysis, Fas transcripts were demonstrated in MIN6N8 cells and pancreatic islet cells by the sequencing analysis of the cloned reverse transcription polymerase chain reaction products using Fas-specific primers. IFN (interferon)-gamma, tumor necrosis factor-alpha, interleukin-1 and their combinations failed to enhance Fas expression. Unsorted activated splenocytes from diabetic NOD mice had cytotoxic T lymphocyte activity of a small degree against IFN-gamma-treated MIN6N8 cells with FasL upregulation. However, agonistic anti-Fas antibody with or without cycloheximide did not exert cytotoxicity against MIN6N8 cells or pancreatic islets. FasL transfectant cells also did not kill MIN6N8 cells. Our data indicate that pancreatic beta-islet cells express a small amount of Fas molecules but Fas molecules do not mediate apoptosis of islet cells at least in vitro.

Animals↗
PubMed1999

Rheumatoid arthritis associated with myelodysplastic syndrome: a case report.

Myelodysplastic syndromes (MDS) are a group of refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. There is increasing recognition of immunological abnormalities in patients with MDS, including defective B- and T-cell function, hyper- or hypogammaglobulinemia and monoclonal gammopathy. MDS have been associated with Sjögren's syndrome, polymyalgia rheumatica, relapsing polychondritis and systemic lupus erythematosus. Although there may be various rheumatologic features, including acute arthritis in MDS, chronic inflammatory arthritis is uncommonly combined. There have been a few reports that described cases of rheumatoid arthritis (RA) concurrent with MDS, but advanced rheumatoid arthritis with typical joint deformities has rarely been reported. We report a case of rheumatoid arthritis with atlantoaxial subluxation combined with refractory anemia in a 31-year-old woman.

Adult↗
PubMed1999

The effect of continuous ambulatory peritoneal dialysis on change in serum leptin.

OBJECTIVE: Elevated serum leptin can contribute to anorexia and poor nutrition in patients with chronic renal failure, because leptin is elevated in chronic renal failure patients with or without dialysis, especially in chronic ambulatory peritoneal dialysis (CAPD) patients. The aim of this study was to find whether leptin can be removed by peritoneal dialysis (PD) and to analyze factors that can affect serum leptin after start of CAPD by observing the change in serum leptin shortly after start of CAPD and its correlation with body mass index (BMI), with serum insulin, and with residual renal function. DESIGN: Twenty patients who started CAPD during the observation period were studied. Serum leptin was measured by radioimmunoassay before start of CAPD, 3-5 days after start of CAPD, and 1 month and 3 months after start of CAPD. Simultaneously, body weight, serum insulin, and residual renal function were measured. To compensate for the circardian rhythm of leptin, removal of leptin was assessed by measuring dialysate leptin divided by average serum leptin before and after a peritoneal equilibration test (PET). RESULTS: Leptin was eliminated by PD with a dialysate-to-serum ratio of 0.16+/-0.07, which was comparable to removal of beta2-microglobulin (0.14+/-0.06). The mean serum leptin concentrations did not decrease after 3-5 days of CAPD (8.4+/-13.1 ng/mL-->11.9+/-18.0 ng/mL) despite its removal by PD, and levels increased markedly to 189% of basal serum leptin 1 month after start of PD and to 260% of basal serum leptin 3 months after start of PD. Correlation coefficients (Spearman's rho) between change of serum leptin and change of BMI, of serum insulin, of glomerular filtration rate (average of urine creatinine clearance and urine urea clearance) were 0.267 (p > 0.05, n = 20), 0.441 (p > 0.05, n = 16), 0.706 (p > 0.05, n = 8) respectively. CONCLUSION: Leptin is removed by peritoneal dialysis. Serum leptin did not decrease in 5 days after the start of PD despite its removal by PD, but increased markedly thereafter, within 3 months after start of PD. We could not find a significant correlation between the change in leptin and the change in BMI. Factors other than fat-mass gain can stimulate leptin increase shortly after start of PD.

Adipose Tissue↗
PubMed1998

Fluorescence derivatizing procedure for 5-hydroxytryptamine and 5-hydroxyindoleacetic acid using 1,2-diphenylethylenediamine reagent and their sensitive liquid chromatographic determination.

A pre-column derivatization method using a fluorogenic reagent, 1,2-diphenylethylenediamine (DPE) was studied for the sensitive HPLC determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), which are biosubstances used in the diagnosis of several diseases. For the quantitative determination, the biogenic indole compounds were converted to their corresponding fluorescent derivatives with DPE in the presence of potassium hexacyanoferrate (III) at room temperature, and then the derivatives were separated by reversed-phase liquid chromatography with fluorescence detection. The chromatographic detection limits of the fluorescent peaks at a signal-to-noise ratio of 3 were 0.3 fmol for 5-HT and 0.2 fmol for 5-HIAA. The proposed method permits the simultaneous quantification of 5-HT and 5-HIAA at concentrations higher than 2.4 nM in human urine without a clean-up procedure.

Chromatography, High Pressure Liquid↗
PubMed1998

Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells.

The effects of bulbocapnine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis in PC12 cells were investigated. Bulbocapnine showed 45.2% inhibition on dopamine content in PC12 cells at a concentration of 20 microM for 12 h. The IC50 value of bulbocapnine was 26.7 microM. Bulbocapnine at concentrations up to 80 microM was not cytotoxic towards PC12 cells. Tyrosine hydroxylase (TH) activity was inhibited by the treatment of bulbocapnine in PC12 cells (24.4% inhibition at 20 microM). Bulbocapnine at 20 microM also decreased the intracellular Ca2+ concentration by 12.9% inhibition relative to control in PC12 cells. However, TH mRNA level was not altered by bulbocapnine treatment. These results suggest that the inhibition of TH activity by bulbocapnine might be involved in at least one component of the reduction of dopamine biosynthesis in PC12 cells.

Animals↗
PubMed1998

Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans.

The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q31. The human homolog of mouse Pou4f3, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8-base pair deletion in the POU homeodomain of human POU4F3 was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.

Adult↗
PubMed1998

Neuropathology of preclinical and clinical late-onset Alzheimer's disease.

We report on the neuropathological examinations of a 74-year-old woman with Alzheimer's disease (AD) and of her 47-year-old nondemented daughter. The brain of the mother showed fully developed pathological changes of AD. By contrast, the brain of the daughter revealed only perineuronal deposition of diffuse amyloid in cerebral cortex and striking abnormalities of the endosomal-lysosomal system, without neurofibrillary, glial, or microglial changes. These observations suggest that amyloid deposition and endosomal-lysosomal changes are early events in late-onset AD and that they may precede the onset of dementia by several decades.

Age of Onset↗
PubMed1998

Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice.

Superoxide dismutase 1 (SOD1), a ubiquitously expressed enzyme, detoxifies superoxide radicals and participates in copper homeostasis. Mutations in this enzyme have been linked to a subset of autosomal dominant cases of familial amyotrophic lateral sclerosis (FALS), a disorder characterized by selective degeneration of motor neurons. Transgenic mice expressing FALS mutant human (Hu) SOD1 at high levels develop a motor neuron disease, indicating that mutant Hu SOD1 gains properties that are particularly toxic to motor neurons. In this report, we demonstrate that transgenic mice expressing Hu SOD1 with the G37R FALS mutation, but not mice expressing wild-type enzyme, develop focal increases in immunoreactivity in the proximal axons of spinal motor neurons. This SOD1 immunoreactivity and immunoreactivity to hypophosphorylated neurofilament H epitopes are found adjacent to small vacuoles in axons. Using metabolic radiolabeling methods, we show that mutant G37R HuSOD1 as well as endogenous mouse SOD1 are transported anterograde in slow component b in motor and sensory axons of the sciatic nerve. Together, these findings suggest that anterogradely transported mutant SOD1 may act locally to damage motor axons.

Animals↗
PubMed1998

Effect of ginseng total saponin on bovine adrenal tyrosine hydroxylase.

Ginseng total saponin (GTS) can modulate dopaminergic activity at both presynaptic and postsynaptic dopamine receptors (Kim et al., 1998). The present study investigated the effect of GTS on the bovine adrenal tyrosine hydroxylase (TH), which catalyze L/tyrosine to DOP. GTS inhibited the bovine adrenal TH by 42.4, 51.5 and 55.3% at concentrations of 40, 80 and 100 micrograms/ml, respectively. The IC50 value of GTS was 77.5 micrograms/ml. GTS exhibited noncompetitive inhibition with a substrate L-tyrosine. The Ki value was 155 micrograms/ml.

Adrenal Glands↗
PubMed1998

Bacillus thuringiensis insecticidal proteins: molecular mode of action.

Growing interest in biorational pesticides has placed the Bacillus thuringiensis insecticidal crystal proteins at the forefront of pesticides for plant genetic engineering. The development of improvement pesticides, both in enhanced activity and broader host range, depends on an understanding of its mechanism of action. This review presents a complete overview of the bacterium and the group of insecticidal proteins known as Cry proteins or delta-endotoxins. The molecular mode of action is described in detail, including the mapping of receptor binding sites by site-directed mutagenesis, the known receptors, and the ion-channel activity of the toxins.

Amino Acid Sequence↗
PubMed1998

Synthesis of sulfonylurea conjugated copolymer via PEO spacer and its in vitro short-term bioactivity in insulin secretion from islets of Langerhans.

In order to reduce the number of immunoprotected islets required in xeno- or allogenic transplants for reversing diabetes, analogues of glyburide (a sulfonylurea), an extremely hydrophobic insulin secretagogue, were synthesized and used in an attempt to produce water soluble sulfonylurea (SU) grafted polymers. After synthesizing various polymers containing glyburide analogues, a poly(N-vinyl-2-pyrrolidone-co-sulfonylurea succinyl PEO (Mw = 3000) acrylate) was found to be soluble in a cell culture medium at pH 7.4. However, solubility was only obtained by decreasing solution pH from 11 to 7.4. When the copolymer was added to the islet cell culture media at a concentration of 5 microg ml(-1) (based on the theoretical SU content of the copolymer), insulin secretion was enhanced by about 30% at low glucose concentrations of 50 and 100 mg dl(-1) compared to the control. This is equivalent to 40-60% bioactivity of glyburide. The polymer's effect on insulin secretion at a higher glucose concentration of 200 mg dl(-1) was not significant. Considering the previous results where a similar but insoluble polymer without a PEO spacer was used and the polymer showed SU bioactivity only at a glucose concentration of 50 mg dl(-1), the observations from this study indicates that the solubility of SU-grafted polymers may affect the binding of SU groups to SU receptors on the pancreatic beta-cells, resulting in improved pharmacodynamic effect of SU.

ATP-Binding Cassette Transporters↗
PubMed1998

Cecropin A - magainin 2 hybrid peptides having potent antimicrobial activity with low hemolytic effect.

In order to obtain peptides having improved antimicrobial activity with low hemolytic effect, a hybrid peptide (CA-MA) composed from cecropin A (1-8) and magainin 2(1-12), and its analogues with amino acid substitutions were designed and synthesized. The antimicrobial activities against bacterial cells and hemolytic activities against human red blood cells were analyzed for each peptide. Secondary structures of the peptides in aqueous solution, 50% trifluoroethanol, and sodium dodecylsulfate micelles were estimated using circular dichroism spectroscopy. The increase in hydrophobicity or alpha-helicity of the peptides correlated with an increase in hemolytic activity rather than antimicrobial activity. The substitution of Leu for Ser at position 16 in CA-MA resulted in a remarkable increase in antimicrobial activity without a significant change in hemolytic activity. Furthermore, the increase in antimicrobial activity of the peptides was not always accompanied by the increase in hemolytic activity.

Amino Acid Sequence↗