Search PubMed⌕ Search

Biomedical subjects

Y C Lee

Publications and source records attributed to Y C Lee.

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

The clearance of theophylline is increased during the initial period of tuberculosis treatment.

OBJECTIVE: To evaluate the effects of combined anti-tuberculosis treatment including isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA), on the pharmacokinetics of theophylline during the initial phase of treatment. DESIGN: Prospective, controlled clinical study. PATIENTS AND METHODS: Twenty patients with pulmonary tuberculosis received 7.35 mg/kg/day of aminophylline intravenously combined with anti-tuberculosis agents. The first theophylline serum concentration was measured before administration of INH, RMP, EMB and PZA, and samples were obtained once daily for 6 consecutive days after initiation of treatment. All patients in this study were non-smokers with normal hepatic and renal function, and they were not given any other drugs that could affect the clearance of theophylline. RESULTS: The concentration and half-life of theophylline was decreased and its clearance was increased significantly at days 5-7 after administration of antituberculosis agents compared to before the therapy was started. CONCLUSIONS: These results suggest that patients with asthma or chronic obstructive pulmonary disease administered combinations of anti-tuberculosis agents and theophylline during the initial phase of tuberculosis treatment should be monitored closely for changes in theophylline concentration, and that the dose of theophylline should be adjusted accordingly.

Adult↗
PubMed2002

Mannose receptor-mediated regulation of serum glycoprotein homeostasis.

Carbohydrates are thought to function as tags that mark circulatory glycoproteins for rapid clearance. To examine the role of the mannose receptor (MR) in glycoprotein clearance, we generated mice genetically deficient in MR. MR-/- mice were defective in clearing proteins bearing accessible mannose and N-acetylglucosamine residues and had elevated levels of eight different lysosomal hydrolases. Proteomic analysis of MR-/- and control mouse sera showed that an additional 4 out of 52 proteins identified were elevated in MR-/- serum. Each of these is up-regulated during inflammation and wound healing. Thus, MR appears to operate as an essential regulator of serum glycoprotein homeostasis.

Animals↗
PubMed2002

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

Adult↗
PubMed2002

Effect of rebamipide in treatment of Helicobacter pylori-associated duodenal ulcer: attenuation of chemokine expression and nitrosative damage.

Production of cytokines along with increased activity of nitric oxide synthase has been implicated as one of the contributing mechanisms of Helicobacter pylori-mediated gastroduodenal diseases. We aimed to evaluate the effect of rebamipide in treating Helicobacter pylori-associated duodenal ulcers in terms of cytokine production and nitrosative damage of the gastric mucosa. In patients with duodenal ulcers, rebamipide or placebo were given randomly after eradication. Mucosal cytokine production was measured by enzyme linked immunoassay, and nitrotyrosine immunoexpression was measured by immunohistochemistry. The inflammatory activity and degree of neutrophil infiltration were graded accordingly. The mucosal production of RANTES, interleukin-8, and TNF-alpha showed a significant decrease after eradication in patients with rebamipide after-treatment. The nitrotyrosine immunoreactivity of gastric epithelium was significantly decreased in the rebamipide group. Rebamipide treatment after eradication resulted in a significant reduction in chemokine production along with nitrotyrosine immunoexpression in Helicobacter pylori-associated duodenal ulcers.

Adult↗
PubMed2002

Autologous peripheral blood stem cell transplantation for peripheral neuropathy secondary to monoclonal gammopathy of unknown significance.

A 40-year-old patient presented with rapidly progressing peripheral neuropathy secondary to monoclonal gammopathy of unknown significance (MGUS). He became severely debilitated, being wheelchair-bound, despite treatment with chemotherapy, intravenous immunoglobulin and plasma exchange. He was subsequently treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). He has made remarkable recovery at 12 months post transplantation. We propose that high-dose chemotherapy and autologous PBSC transplantation may have a role in the treatment of severe, progressive and treatment-resistant MGUS-related peripheral neuropathy.

Adult↗
PubMed2002

Paclitaxel plus carboplatin, compared with paclitaxel plus gemcitabine, shows similar efficacy while more cost-effective: a randomized phase II study of combination chemotherapy against inoperable non-small-cell lung cancer previously untreated.

BACKGROUND: Paclitaxel (Taxol) plus carboplatin (PC) has shown activity in the treatment of advanced non-small-cell lung cancer (NSCLC). Non-platinum-containing combination chemotherapy, such as paclitaxel plus gemcitabine (PG), has also demonstrated reasonable efficacy. Our aim here was to evaluate the clinical efficacy and cost-effectiveness of PC versus PG in chemo-naive. advanced NSCLC patients. PATIENTS AND METHODS: Ninety (68 male, 22 female) patients were enrolled from August 1999 to August 2000. The performance status was one in 29 patients and two in 16 patients of the PC group, and one in 24 patients and two in 21 patients of the PG group. Seventeen patients had stage IIIb disease and 28 patients stage IV disease in the PC group: 18 patients had stage IIIb disease and 27 patients stage IV disease in the PG group (New International Staging System). Treatment consisted of P 175 mg/m2 and C at AUC = 7 (predicted using measured clearances and the Calvert formula) intravenous infusion (i.v.) on day 1, or P 175 mg/m2 i.v. on day 1 and G 1000 mg/m2 i.v. on days 1 and 8, every 3 weeks. RESULTS: In all, 175 cycles of PC and 184 cycles of PG were given in the PC and PG groups, respectively. The median treatment cycle was four cycles in both groups. All the patients were assessable for toxicity and response measurement. There were three complete responses and 15 partial responses (overall 40%) in the PC group, and no complete response, but 18 partial responses (overall 40%) in the PG group. WHO grades 3/4 leukopenia, anemia and thrombocytopenia occurred in six (13.3%), seven (15.5%) and five patients (11.1%) in the PC group; and in four (8.9%), six (13.3%) and 0 patients in the PG group, respectively. Two patients in each group suffered from grade 3 peripheral neuropathy. Other non-hematological toxicities were mild and few. Median survival time was 14.1 months in the PC group and 12.6 months in the PG group. One-year survival was 50.7% in the PC group and 53.3% in the PG group. The PG group had a higher total expense and expended more days undergoing treatment than the PC group (P = 0.034 and 0.069, respectively). CONCLUSIONS: Both PC and PG combination chemotherapy produce a similar efficacy in the treatment of NSCLC. However, PC is more cost-effective than PG.

Adult↗
PubMed2002

Expression of DAZL protein in the human corpus luteum.

The DAZL gene and its homologues are required for the development of male and female germ cells in different species. However, their role in other aspects of human reproduction is not known. We have generated a polyclonal antibody to the DAZL protein and developed a sensitive standard curve quantitative-competitive-RT-PCR assay to characterize the expression of DAZL in the human corpus luteum (CL). DAZL transcripts are expressed in the CL, but the concentrations decreased with advancing luteal phase. In accordance with the mRNA data, DAZL protein was most abundant in the early phase CL. Immunohistochemical staining showed DAZL protein in the cytoplasm of granulosa-luteal cells. The distinct expression pattern of DAZL protein in the human CL may play an important role in the regulation of luteal function.

Animals↗
PubMed2001

Modification of octamer binding transcriptional factor is related to H2B histone gene repression during dimethyl sulfoxide-dependent differentiation of HL-60 cells.

Transcriptional regulation of H2B histone gene during dimethyl sulfoxide (DMSO)-dependent differentiation of HL-60 cells has been investigated using DNase I footprinting and DNA mobility shift assay. The level of histone H2B mRNA showed a slight decline at 2 days and hardly detectable at 4 days after DMSO treatment. H2B histone mRNA was repressed in proportion to the concentration of DMSO. In DNase I footprinting analysis, one nuclear factor (octamer binding transcription factor, OTF) bound at -42 bp (octamer motif, ATTTGCAT) in undifferentiated HL-60 cells. The binding pattern of OTF was unchanged during DMSO-dependent differentiation. One protein complex (OTF) was detected by DNA mobility shift assay in undifferentiated HL-60 cells. The mobility of OTF was partially retarded during DMSO-dependent differentiation and the retardant OTF was not newly synthesized protein. These results suggest that the posttranslational modification of OTF may be responsible for the repression of H2B histone gene during DMSO-dependent differentiation of HL-60 cells.

Binding Sites↗
PubMed2001

YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components.

YC-1 [3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole] is an allosteric activator of soluble guanylyl cyclase (sGC). YC-1 increases the catalytic rate of the enzyme and sensitizes the enzyme toward its gaseous activators nitric oxide or carbon monoxide. In other studies the administration of YC-1 to experimental animals resulted in the inhibition of the platelet-rich thrombosis and a decrease of the mean arterial pressure, which correlated with increased cGMP levels. However, details of YC-1 interaction with sGC and enzyme activation are incomplete. Although evidence in the literature indicates that YC-1 activation of sGC is strictly heme-dependent, this report presents evidence for both heme-dependent and heme-independent activation of sGC by YC-1. The oxidation of the sGC heme by 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one completely inhibited the response to NO, but only partially attenuated activation by YC-1. We also observed activation by YC-1 of a mutant sGC, which lacks heme. These findings indicate that YC-1 activation of sGC can occur independently of heme, but that activation is substantially increased when the heme moiety is present in the enzyme.

Base Sequence↗
PubMed2001

Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells.

BACKGROUND: Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL(1-0), CL(1-1), CL(1-5), and CL(1-5)-F(4) in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize. METHODS: We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL(1-5) cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). All statistical tests were two-sided. RESULTS: Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL(1-5) cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P< .001). During interphase, CRMP-1 protein was present uniformly throughout the cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was associated with mitotic spindles, centrosomes, and the midbody (in late telophase). Real-time RT-PCR of lung cancer specimens showed that reduced expression of CRMP-1 was statistically significantly associated with advanced disease (stage III or IV; P = .010), lymph node metastasis (N1, N2, and N3; P =.043), early postoperative relapse (P = .030), and shorter survival (P = .016). CONCLUSIONS: CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion-suppressor gene.

Actins↗
PubMed2001

The structural and functional organization of the yeast mediator complex.

The Mediator complex of Saccharomyces cerevisiae is required for diverse aspects of transcription by RNA polymerase II (pol II). Mediator is composed of two functionally distinct subcomplexes, Rgr1 and Srb4. To identify the structures and functions of each subcomplex, we expressed recombinant proteins for each subunit and assayed their interactions with each other and with basal transcription proteins. The Rgr1 subcomplex is composed of the Gal11 module, which binds activators, and the Med9/10 module. The Med9/10 module is required for both transcriptional activation and repression, and these activities appear to be carried out by two submodules. Proteins in the Med9 submodule interact physically and genetically with Srb10/11, suggesting that the Med9 submodule mediates the repression of pol II. Purified recombinant Srb4 subcomplex stimulated basal transcription of pol II but had little effect on activated transcription and phosphorylation of the C-terminal domain of the Rpb1 subunit of pol II. Both subcomplexes of Mediator interacted with a distinct set of basal transcription factors and pol II. The modular organization of Mediator and the associated functions suggest that the Mediator complex may recruit and/or stabilize the preinitiation complex through several points of contact with transcriptional regulators and basal transcription factors.

Fungal Proteins↗
PubMed2001

Risk of betel chewing for oesophageal cancer in Taiwan.

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

Adult↗
PubMed2001

Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5'-untranslated region.

GM3 synthase, which transfers CMP-NeuAc with an alpha2,3-linkage to a galactose residue of lactosylceramide, plays a key role in the biosynthesis of all complex gangliosides. In this study, cDNA and genomic clones encoding human GM3 synthase (hST3Gal V) were isolated, and the structural organization of the gene was determined. The hST3Gal V cDNA was identical in the coding region with cDNA that has been cloned previously from the HL-60 cells but different in the 5'-untranslated region (UTR). The hST3Gal V gene consisted of nine exons, which span approximately 44 kb, with exons ranging in size from 112 to 1242 bp. The coding region was located in exons 4-9, and all exon-intron boundaries except the acceptor site of intron 1 followed the GT-AG rule. The expression of this gene was highly restricted in both human fetal and adult tissues. By comparison of the nucleotide sequences of the genomic DNA with cDNA sequences including 5'-RACE products, we identified four isoforms (types 1-4) of the hST3Gal V mRNA that differ only in the 5'-UTR. Structural analysis of these isoforms suggests that mRNA isoforms of hST3Gal V are produced by a combination of alternative splicing and alternative promoter utilization.

5' Untranslated Regions↗
PubMed2001

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Adult↗
PubMed2001

Transcriptional regulation of human 3'-phosphoadenosine 5'-phosphosulfate synthase 1.

Sulfonation, which is essential for normal growth, development and maintenance of the internal milieu, requires the universal sulfonate donor molecule 3'-phosphoadenosine 5'-phosphosulfate (PAPS) produced from ATP and inorganic sulfate by two bifunctional PAPS synthase isozymes. The gene for PAPS synthase 1 containing neither a TATA nor a CCAAT box was found to be under the influence of the Sp1 family of transcription factors. Multiple GC/GT boxes are present in the proximal promoter region and deletion analysis implicated their involvement in transcription, a finding supported by mutational analysis of specific GC/GT boxes. Nuclear extract of SW13 cells, which highly express PAPS synthase 1, contains proteins that bind to probes possessing specific GC/GT boxes; furthermore, the presence of Sp1, Sp2, and Sp3 proteins in nuclear extracts was confirmed by supershift analysis. Cotransfection experiments using SL2 cells yielded additional support for the involvement of Sp1 in transcriptional regulation of the PAPS synthase 1 gene; the involvement of Sp2 and/or Sp3 is presently unclear.

Animals↗
PubMed2001

Determination of nucleotides and sugar nucleotides involved in protein glycosylation by high-performance anion-exchange chromatography: sugar nucleotide contents in cultured insect cells and mammalian cells.

We have developed a simple and highly sensitive HPLC method for determination of cellular levels of sugar nucleotides and related nucleotides in cultured cells. Separation of 9 sugar nucleotides (CMP-Neu5Ac, CMP-Neu5Gc, CMP-KDN, UDP-Gal, UDP-Glc, UDP-GalNAc, UDP-GlcNAc, GDP-Fuc, GDP-Man) and 12 nucleotides (AMP, ADP, ATP, CMP, CDP, CTP, GMP, GDP, GTP, UMP, UDP, and UTP) was examined by reversed-phase HPLC and high-performance anion-exchange chromatography (HPAEC). Although the reversed-phase HPLC, using an ion-pairing reagent, gave a good separation of the 12 nucleotides, it did not separate sufficiently the sugar nucleotides for quantification. On the other hand, the HPAEC method gave an excellent and reproducible separation of all nucleotides and sugar nucleotides with high sensitivity and reproducibility. We applied the HPAEC method to determine the intracellular sugar nucleotide levels of cultured Spodoptera frugiperda (Sf9) and Trichoplusia ni (High Five, BTN-TN-5B1-4) insect cells, and compared them with those in Chinese hamster ovary (CHO-K1) cells. Sf9 and High Five cells showed concentrations of UDP-GlcNAc, UDP-Gal, UDP-Glc, GDP-Fuc, and GDP-Man equal to or higher than those in CHO cells. CMP-Neu5Ac was detected in CHO cells, but it was not detected in Sf9 and High Five cells. In conclusion, the newly developed HPAEC method could provide valuable information necessary for generating sialylated complex-type N-glycans in insect or other cells, either native or genetically manipulated.

Animals↗