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Biomedical subjects

N H Lee

Publications and source records attributed to N H Lee.

At least 19 recordsLinked to original sources
PubMed2001

Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray.

Metastasis represents a crucial transition in disease development and progression and has a profound impact on survival for a wide variety of cancers. Cell line models of metastasis have played an important role in developing our understanding of the metastatic process. We used a 19,200-element human cDNA microarray to profile transcription in three paired cell-line models of colorectal tumor metastasis. By correlating expression patterns across these cell lines, we have identified 176 genes that appear to be differentially expressed (greater than 2-fold) in all highly metastatic cell lines relative to their reference. An analysis of these genes reiterates much of our understanding of the metastatic process and suggests additional genes, many of previously uncharacterized function, that may be causatively involved in, or at least prognostic of, metastasis. Northern analysis of a limited number of these genes validates the observed pattern of expression and suggests that further investigation and functional characterization of the identified genes is warranted.

Biomarkers, Tumor↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

A new antioxidant monoterpene glycoside, alpha-benzoyloxypaeoniflorin from Paeonia suffruticosa.

Alpha-benzoyloxypaeoniflorin (1), a new antioxidant monoterpene alpha-glycoside anomer was isolated from Paeonia suffruticosa along with known compounds, beta-benzoyloxypaeoniflorin (2), paeonolide, paeoniflorin and mudanpioside H. The structure of 1 has been determined by comparing spectral data with those of beta-benzoyloxypaeoniflorin (2). Compound 1 exhibited moderately potent radical scavenging activity on DPPH radical.

Antioxidants↗
PubMed2001

Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation.

To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.

Animals↗
PubMed2001

Microarray analysis of the in vivo effects of hypophysectomy and growth hormone treatment on gene expression in the rat.

Complementary DNA microarrays containing 3000 different rat genes were used to study the consequences of severe hormonal deficiency (hypophysectomy) on the gene expression patterns in heart, liver, and kidney. Hybridization signals were seen from a majority of the arrayed complementary DNAs; nonetheless, tissue-specific expression patterns could be delineated. Hypophysectomy affected the expression of genes involved in a variety of cellular functions. Between 16-29% of the detected transcripts from each tissue changed expression level as a reaction to this condition. Chronic treatment of hypophysectomized animals with human GH also caused significant changes in gene expression patterns. The study confirms previous knowledge concerning certain gene expression changes in the above-mentioned situations and provides new information regarding hypophysectomy and chronic human GH effects in the rat. Furthermore, we have identified several new genes that respond to GH treatment. Our results represent a first step toward a more global understanding of gene expression changes in states of hormonal deficiency.

Animals↗
PubMed2000

Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosine-1-phosphate receptors.

The previously cloned rat nerve growth factor-regulated G protein-coupled receptor NRG-1 (Glickman, M., Malek, R. L., Kwitek-Black, A. E., Jacob, H. J., and Lee N. H. (1999) Mol. Cell. Neurosci. 14, 141-52), also known as EDG-8, binds sphingosine-1-phosphate (S1P) with high affinity and specificity. In this paper we examined the signal transduction pathways regulated by the binding of S1P to EDG-8. In Chinese hamster ovary cells heterologously expressing EDG-8, S1P inhibited forskolin-induced cAMP accumulation and activated c-Jun NH2-terminal kinase. Surprisingly, S1P inhibited serum-induced activation of extracellular regulated protein kinase 1 and 2 (ERK1/2). Treatment with pertussis toxin, which ADP-ribosylates and inactivates G(i), blocked S1P-mediated inhibition of cAMP accumulation, but had no effect on c-Jun NH2-terminal kinase activation or inhibition of ERK1/2. The inhibitory effect of S1P on ERK1/2 activity was abolished by treatment with orthovanadate, suggesting the involvement of a tyrosine phosphatase. A subunit selective [35S] guanosine 5'-3-O-(thio)triphosphate binding assay demonstrates that EDG-8 activated G(i/o) and G12 but not Gs and G(q/11) in response to S1P. In agreement, EDG-8 did not stimulate phosphoinositide turnover or cAMP accumulation. The ability of S1P to induce mitogenesis in cells expressing the EDG-1 subfamily of G protein-coupled receptors is well characterized. In contrast, S1P inhibited proliferation in Chinese hamster ovary cells expressing EDG-8 but not empty vector. The antiproliferative effect, like S1P-mediated ERK1/2 inhibition, was orthovanadate-sensitive and pertussis toxin-insensitive. Our results indicate that EDG-8, a member of the EDG-1 subfamily, couples to unique signaling pathways.

Cell Division↗
PubMed2000

Identification of c-myc responsive genes using rat cDNA microarray.

c-Myc functions through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Myc-responsive genes by comparing gene expression profiles between c-myc null and c-myc wild-type rat fibroblast cells and between c-myc null and c-myc null cells reconstituted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes responsive to c-myc when comparing wild-type or reconstituted cells with the null cells. The plurality of the named c-Myc-responsive genes that were up-regulated, including 30 ribosomal protein genes, are involved in macromolecular synthesis and metabolism, suggesting a major role of c-Myc in the regulation of protein synthetic and metabolic pathways. When ectopically overexpressed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming functions of c-myc may be separable.

Animals↗
PubMed2000

Long-term outcomes of minor dissection at the edge of stents detected with intravascular ultrasound.

We evaluated the influences of minor edge dissections on late angiographic in-stent restenosis in 327 patients with 348 lesions (281 lesions without edge dissection and 67 lesions [19.3%] with edge dissection); the angiographic restenosis rate was 29.9% in the lesions with edge dissections versus 25.3% without edge dissections (p = 0.540). The minor non-flow-limiting dissections at the edge of stents may not be associated with the development of late angiographic in-stent restenosis.

Coronary Angiography↗
PubMed2000

Effects of cilostazol on angiographic restenosis after coronary stent placement.

This study evaluates the impact of cilostazol on post-stenting restenosis. Cilostazol is a potent antiplatelet agent with antiproliferative properties. Few data are available about the effect of cilostazol on poststenting restenosis. Four hundred nine patients (494 lesions) who were scheduled for elective stenting were randomized to receive aspirin plus ticlopidine (group I, n = 201, 240 lesions) or aspirin plus cilostazol (group II, n = 208, 254 lesions), starting 2 days before stenting. Ticlopidine was given for 1 month and cilostazol for 6 months. Follow-up angiography was performed at 6 months, and clinical evaluation at regular intervals. Baseline characteristics were similar between the 2 groups. The procedural success rate was 99.6% in group I and 100% in group II. There were no cases of stent thrombosis after stenting. Angiographic follow-up was performed in 380 of the 494 eligible lesions and the angiographic restenosis rate was 27% in group I and 22.9% in group II (p = NS). However, diffuse type in-stent restenosis was more common in group I than in group II (54.2% vs 26.8%, respectively, p <0.05). In diabetic patients, the angiographic restenosis rate was 50% in group I and 21.7% in group II (p <0.05). Clinical events during follow-up did not differ between the 2 groups. In conclusion, aspirin plus cilostazol seems to be an effective antithrombotic regimen with comparable results to aspirin plus ticlopidine, but it does not reduce the overall angiographic restenosis rate after elective coronary stenting.

Angioplasty, Balloon, Coronary↗
PubMed2000

Intravascular ultrasonic predictors of angiographic restenosis after long coronary stenting.

The intravascular ultrasound (IVUS) criteria for stent optimization have not been determined in stenting long lesions. We evaluated the predictors of angiographic restenosis and compared it with stent lumen cross-sectional area (CSA) and stent length between short (stent length <20 mm) and long (> or =20 mm) coronary stenting. IVUS-guided coronary stenting was successfully performed in 285 consecutive patients with 304 native coronary lesions. Six-month follow-up angiogram was performed in 236 patients (82.8%) with 246 lesions (80.9%). Results were evaluated using conventional (clinical, angiographic, and IVUS) methods. The overall angiographic restenosis rate was 22.8% (56 of 246 lesions) (short stent 17.6% vs. long stent 32.2%, p = 0.009). Using multivariate logistic regression analysis, the independent predictors of angiographic restenosis were the IVUS stent lumen CSA (odds ratio 1.51, 95% confidence intervals 1.18 to 1.92, p = 0.001) and stent length (odds ratio 0.95, 95% confidence intervals 0.91 to 1.00, p = 0.039). The angiographic restenosis rate was 54.8% for stent lumen CSA of <5.0 mm2 (short stent 37.5% vs. long stent 73.3%, p = 0.049), 27.4% for CSA between 5.0 and 7.0 mm2 (short stent 24.1% vs. long stent 31.7%, p = 0.409), 10.5% for CSA between 7.0 and 9.0 mm2 (short stent 10.0% vs. long stent 12.5%, p = 0.772), and 11.4% for stent lumen CSA of > or =9.0 mm2 (short stent 10.4% vs. long stent 13.3%, p = 0.767) (p = 0.001). Compared with short coronary stenting, long coronary stenting is effective treatment modality to cover long lesions with comparable long-term clinical outcomes in cases of stent lumen CSA of > or =7.0 mm2. Regardless of the stent length, the most important factor determining angiographic restenosis was the IVUS stent lumen CSA in relatively large coronary artery lesions.

Blood Vessel Prosthesis Implantation↗
PubMed2000

Tuberculous cellulitis.

We report a case of cutaneous tuberculosis presenting as cellulitis. The patient was a 63-year-old Korean woman who also had diabetes mellitus and a 20-year-history of oral corticosteroid medication prescribed for arthralgia. In addition, she had had pulmonary tuberculosis 20-year previously for which she received systemic treatment for 1 year. Her clinical cellulitis failed to respond to antibiotic therapy. Subsequent investigations, using histopathology and polymerase chain reaction, established an alternative diagnosis of cutaneous tuberculosis. The skin eruption cleared after treatment with isoniazid, rifampicin, ethambutol and pyrazinamide. This case represents a most unusual presentation of tuberculosis in the skin. The atypical features may reflect the patient's general medical state.

Antitubercular Agents↗
PubMed2000

Apocrine poroma with sebaceous differentiation.

Poromas have been classified as eccrine neoplasms, but several recent reports of poroid tumors with sebaceous, follicular, and apocrine differentiation have challenged this concept. We report a case of apocrine poroma with sebaceous differentiation. A 69-year-old man presented with an asymptomatic elevated erythematous plaque. Histopathology revealed cellular nests composed of cuboidal poroid cells and sebocytes. The nests varied in size and were entirely intraepidermally arranged in a growth pattern similar to that of hidroacanthoma simplex. Given the common embryologic origin of folliculosebaceous and apocrine units, we believe that this lesion represents an apocrine poroma with sebaceous differentiation.

Acrospiroma↗
PubMed1999

Adenosine A(2A) receptor mRNA regulation by nerve growth factor is TrkA-, Src-, and Ras-dependent via extracellular regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase.

We have shown previously that nerve growth factor (NGF) down-regulates adenosine A(2A) receptor (A(2A)AR) mRNA in PC12 cells. To define cellular mechanisms that modulate A(2A)AR expression, A(2A)AR mRNA and protein levels were examined in three PC12 sublines: i) PC12nnr5 cells, which lack the high affinity NGF receptor TrkA, ii) srcDN2 cells, which overexpress kinase-defective Src, and iii) 17.26 cells, which overexpress a dominant-inhibitory Ras. In the absence of functional TrkA, Src, or Ras, NGF-induced down-regulation of A(2A)AR mRNA and protein was significantly impaired. However, regulation of A(2A)AR expression was reconstituted in PC12nnr5 cells stably transfected with TrkA. Whereas NGF stimulated the mitogen-activated protein kinases p38, extracellular regulated kinase 1 and 2 (ERK1/ERK2), and stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) in PC12 cells, these kinases were activated only partially or not at all in srcDN2 and 17.26 cells. Inhibiting ERK1/ERK2 with PD98059 or inhibiting SAPK/JNK by transfecting cells with a dominant-negative SAPKbeta/JNK3 mutant partially blocked NGF-induced down-regulation of A(2A)AR expression in PC12 cells. In contrast, inhibiting p38 with SB203580 had no effect on the regulation of A(2A)AR mRNA and protein levels. Treating SAPKbeta/JNK3 mutant-transfected PC12 cells with PD98059 completely abolished the NGF-induced decrease in A(2A)AR mRNA and protein levels. These results reveal a role for ERK1/ERK2 and SAPK/JNK in regulating A(2A)AR expression.

Animals↗
PubMed1999

Molecular cloning, tissue-specific expression, and chromosomal localization of a novel nerve growth factor-regulated G-protein- coupled receptor, nrg-1.

A novel and differentially expressed gene, named nrg-1, was identified by EST expression profiling and subsequently isolated as a 2.2-kb full-length clone from a rat PC12 cell cDNA library. Sequence analysis reveals that nrg-1 encodes a putative seven transmembrane spanning domain protein with structural features characteristic of receptors belonging to the G-protein-coupled receptor gene superfamily. The 400-amino-acid protein encoded by nrg-1 exhibits a high degree of sequence identity (40-44%) to the Edg receptor family; members include Edg-1, Edg-2, Edg-3, Edg-4, and H218. Both Northern analysis andEST expression profiling revealed that whole-tissue distribution of nrg-1 mRNA is restricted, found almost exclusively in brain. Transcripts of nrg-1 could be ubiquitously detected in different regions, with very prominent expression in lower brain regions such as the midbrain, pons,medulla, and spinal cord. In PC12 cells, nerve growth factor induces neuronal differentiation and repressed expression of nrg-1. Two other agents that differentiate PC12 cells, fibroblast growth factor and dibdutyryl cAMP, down-regulated nrg-1 mRNA levels. Epidermal growth factor, and agent that does not induce differentiation, did not repress nrg-1 mRNA levels. In a PC12 cell mutant that is deficient in protein kinase A activity (AB.11), all three differentiating agents were unable to down-regulate nrg-1 mRNA. Hence, protein kinase A appears to be an obligatory cellular component in nrg-1 mRNA regulation. Chromosomal mapping employing a rat somatic cell readiation hybrid panel demonstrated that nrg-1 is linked to marker D8Rat54 and tightly associated with H218 on chromosome 8.

Amino Acid Sequence↗
PubMed1999

An unusual case of colonic duplication causing chronic constipation in a child.

A case of colonic duplication producing chronic constipation in a 8-year-old boy is presented. Barium enema studies demonstrated a long tubular shape of duplication that branched out from the lower part of descending colon. Successful surgical treatment was achieved by excision of the duplication with a portion of adjacent bowel and an end-to-end anastomosis.

Child↗
PubMed1999

5-Oxonoraporphines from Mitrephora cf. maingayi.

Two new 5-oxonoraporphines, 1 and 2, together with three known compounds, ouregidione, 3-methoxycepharadione B, and isoelemicin, have been isolated from the bark of Mitrephora cf. maingayi. Structures of 1 and 2 were determined to be 1,2,3-trimethoxy-5-oxonoraporphine and 1,2-dimethoxy-3-hydroxy-5-oxonoraporphine on the basis of NMR and MS studies.

Animals↗
PubMed1999

A case of pre-Sézary syndrome preceded by hand lesions.

Pre-Sézary syndrome is an erythroderma with a chronic course, clinical findings of Sézary syndrome, lymphocytic subepidermal band infiltration at times, and repeated cycles of circulating Sézary cells of less than 1,000 cells/mm3. Duration of the pre-existing skin diseases preceding pre-Sézary erythroderma varies from a few weeks to 20 years. Before the erythroderma develops, these patients are diagnosed with contact dermatitis, neurodermatitis, chronic dermatitis, atopic dermatitis, or asteatotic eczema. Hand lesion also precedes the pre-Sézary erythroderma. This condition has been controlled by three cycles of chemotherapy consisting of vincristine, cytoxan, doxorubicin, and prednisolone. We describe a case of pre-Sézary syndrome preceded by hand lesion and treated with chemotherapy.

Adult↗