Biomedical subjects

W C Chang

Publications and source records attributed to W C Chang.

At least 91 records · Page 5Linked to original sources

PubMed2000

Lewis (FUT3) genotypes in Taiwanese, Thai, and Filipino populations.

The Lewis (Le) blood type comprises two major antigens, Le(a) and Le(b), which are encoded by alpha (1,2)-fucosyltransferase (FUT2) and a (1,3/1,4)-fucosyl-transferase (FUT3). In this study, we analyzed the mutations of FUT3 in Taiwanese, Thai, and Filipino populations and correlated these with serologic phenotypes. One hundred and thirty-seven Taiwanese, 71 Thai, and 125 Filipino were studied unselectively. The frequency of the normal and four other mutant alleles for Taiwanese, Thai, and Filipino, respectively, were as follows: 187/274 (68.2%), 87/142 (61.3%), and 160/250 (64.0%) were wild type (Le); 14/274 (5.1%), 1/142 (0.7%), and 1/250 (0.4%) were a T202C/C314T mutation (le202,314); 35/274 (12.8%), 15/142 (10.6%), and 22/250 (8.8%) had the G508A mutation (le508); and 38/274 (13.9%), 39/142 (27.4%), and 67/250 (26.8%) carried the T1067A mutation (le1067). The le445 and le1007 were not detected in this study. Our result provided the first genetic data of the FUT3 gene in these three populations, and the frequency distribution of mutant alleles among Taiwanese, Thai, and Filipinos demonstrates a significant difference (P<0.001). In our study, the le202,314 mutation had considerable frequency in the Taiwanese, but the le1067 mutation had a higher frequency in Thai and Filipinos.

Adult↗

PubMed2000

Salivary and serum antibody response to Streptococcus mutans antigens in humans.

Humoral immunity against Streptococcus mutans infection was analyzed in caries-active and caries-free young adults by immunoblotting. All volunteers from both groups had detectable salivary immunoglobulin A (IgA) and serum IgG antibodies, with similar profiles. They could be classified on the basis of relative intensity of the immunoblot bands into categories of high or low responders. Common protein antigens with molecular weight ranging from approximately 45 to 190 kDa could be found either extracellularly or associated with the cell wall of S. mutans cultured in vitro. The predominant reactive antigens recognized by both IgA and IgG were of proteins around 63 and 60 kDa. Detection of IgA antibodies to the various antigens of S. mutans in individual saliva samples did not always correlate with serum IgG antibody profiles. In addition, distinct bands, which reacted preferentially with either IgA or IgG, could be detected by antibodies from specific subjects. Differential reactivities of salivary IgA and serum IgG antibodies to two, cell-wall associated protein antigens around 33 and 36 kDa were found in caries-active and caries-free young adults; 30.8% of caries-free subjects and 12% of caries-active subjects (P < 0.01) exhibited detectable antibody response to these antigens. This difference was not attributable to variations in antibody levels, since antibody response to these proteins were still detectable in some caries-free but not caries-active individuals whose levels of antibodies to other antigens were low. Thus, a new antibody profile which correlates with dental caries disease activity has been identified in a selected population. Differences in mucosal and systemic immune responses to S. mutans seem to be both antigen and host dependent.

Adolescent↗

PubMed2000

Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells.

Regulation of arachidonate metabolism in human epidermoid carcinoma A431 cells by phospholipid hydroperoxide glutathione peroxidase (PHGPx) and cytosolic glutathione peroxidase (GPx1) was studied. In order to study the effect of reduced glutathione (GSH) on the catalysis regulation of these oxygenation enzymes, diethyl maleate was used to deplete the intracellular GSH. In the presence of 13-hydroperoxyoctadecadienoic acid, the enzymatic catalysis of cyclooxygenase and 12-lipoxygenase was significantly increased in the GSH-depleted cells. In terms of the inhibitory effect on 12-lipoxygenase, PHGPx was more sensitive to GSH concentrations than GPx1. Inhibition of PHGPx activity by the treatment of cells with antisense oligonucleotide of PHGPx mRNA increased the enzymatic catalysis of both cyclooxygenase and 12-lipoxygenase. In conclusion, the results indicate that catalysis of cyclooxygenase and 12-lipoxygenase in A431 cells was regulated by redox-reaction, and PHGPx seems to play an important role in the controlling of these reactions.

Arachidonate 12-Lipoxygenase↗

PubMed2000

Prognostic value of p53 expression in stage IB1 cervical carcinoma.

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Adult↗

PubMed2000

Essential role of mitogen-activated protein kinase pathway and c-Jun induction in epidermal growth factor-induced gene expression of human 12-lipoxygenase.

The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kinase (JNK) in a time-dependent manner. Treatment of the cells with an mitogen-activated protein kinase kinase inhibitor, PD098059 (30 microM), inhibited the EGF- and pSV2ras-induced expression of 12-lipoxygenase mRNA. Transfection of the cells with Ras, ERK2, Rac, JNK dominant negative mutants pMMrasDN, K52R ERK2, RacN17, and mJNK all inhibited the EGF-induced promoter activation of the 12-lipoxygenase gene. EGF induced the expression of c-Jun and the activity of transcription factor activator protein 1 in cells, and these effects were blocked by the treatment with K52R ERK2 and mJNK. Overexpression of c-Jun increased the expression of 12-lipoxygenase mRNA and enzyme activity. Furthermore, the Sp1-binding sites in the promoter region of the 12-lipoxygenase gene were requisite for c-Jun response, which was similar to that previously observed in EGF response. The results indicate that the EGF-induced expression of 12-lipoxygenase in A431 cells was mediated through the Ras-ERK and Ras-Rac-JNK signal pathways. Subsequent induction of c-Jun led by ERK and JNK activation was essential for this EGF response.

Arachidonate 12-Lipoxygenase↗

PubMed2000

Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.

We have recently demonstrated that overexpression of PKC beta(II) renders transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation and aberrant crypt foci formation. In order to further investigate the ability of PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization of PKC beta(II) with respect to cell proliferation and apoptosis along the entire colonic crypt axis following carcinogen and diet manipulation. Rats were provided diets containing either corn oil [containing n-6 polyunsaturated fatty acids (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After 16 weeks, an intermediate time point when no macroscopic tumors are detected, colonic sections were utilized for immunohistochemical image analysis and immunoblotting. Cell proliferation was measured by incorporation of bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II) staining was localized to the upper portion of the crypt. In comparison, proximal crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05) PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle and lower tertiles). There was also an interaction (P < 0.05) between dietary fat and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin > corn/cellulose) in all regions of the distal colonic crypt. With respect to colonic cell kinetics, proliferation paralleled the increase in PKC beta(II) expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal surface was inversely proportional to PKC beta(II) expression in the upper tertile. These results suggest that an elevation in PKC beta(II) expression along the crypt axis in the distal colon is linked to enhancement of cell proliferation and suppression of apoptosis, predictive intermediate biomarkers of tumor development. Therefore, select dietary factors may confer protection against colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II) expression.

Animals↗

PubMed2000

Gender prevalence in twin-twin transfusion syndrome.

BACKGROUND: This study aimed to determine the gender prevalence of fetuses complicated with twin-twin transfusion syndrome (TTTS). METHODS: All cases of TTTS corresponded with the following major criteria: a single placenta, monochorion, the same gender, and a combination of polyhydramnios-oligohydramnios. At least one of three minor criteria were required for the establishment of TTTS, including a stuck twin, a birth weight discordance exceeding 20%, and hemoglobin difference > 5 g/dl. RESULTS: Fifty-six twin pregnancies met the above criteria, of which 33 (58.9%) twin pairs were female. The female tendency existed, but there was a non-significant difference. Mean gestational age at diagnosis was 20.2 +/- 3.2 weeks. The birth weight discordance exceeding 20% was present in 50 of 56 (89.3%), and mean growth discordance was 32% +/- 8%. A stuck twin was noted in 37 of 56 cases (66.1%). The mortality of fetuses or neonates was 34.8% (39/112), including 8 (7.1%) fetal deaths and 31 (27.6%) neonatal deaths. There were no differences in maternal age, parity, or gestational age of delivery between male and female pregnancies. CONCLUSION: Although the female preponderance did not reach statistical significance, the female tendency might still exist after a larger series analysis. The female tendency may be the result of the gender difference in monochorionic twins. The gender difference could provide research implications and a diagnostic warning for clinicians in monochorionic twin pregnancies before the presence of TTTS.

Female↗

PubMed2000

Temporal evolution in the management of acute ST elevation myocardial infarction: the seven-year GUSTO experience from canada and the united states. The North American GUSTO-I and GUSTO-III investigators.

BACKGROUND: Temporal changes in baseline characteristics, treatment and clinical outcomes of patients presenting with acute ST elevation myocardial infarction in Canada and the United States have not been examined comprehensively over time. OBJECTIVES: To evaluate baseline characteristics, process of care and clinical outcomes. Also, to explore whether earlier process-of-care differences between Canada and the United States had changed and, if so, whether they influenced clinical outcomes. PATIENTS AND METHODS: A total of 13, 888 American and 3011 Canadian patients enrolled in 184 American and 38 Canadian hospitals that participated in both the Global Utilization of Streptokinase and Tissue Plasminogen Activator (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial (1990 to 1993) and the Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial (1995 to 1997) were studied. Logistic regression was used to identify significant prognostic factors, to assess illness severity at hospital presentation and to classify trends between Canada and the United States. RESULTS: In both countries, illness severity on admission increased, door-to-needle time for thrombolysis was reduced, intensive care unit stay was shortened and hospital stay decreased from GUSTO-I to GUSTO-III. Whereas the administration of oral nitrates, calcium blockers and beta-blockers at discharge converged over time between countries, the disparity in the use of angiography and revascularization widened; the rise in American revascularization rate was most evident in patients without in-hospital ischemia. The 30-day and one-year mortality rates were comparable and declined nonsignificantly in both countries. CONCLUSIONS: Despite increased illness severity and varying medication and procedure rates, there was no increase over time in 30-day or one-year mortality; this remained comparable between countries throughout the seven-year observation period.

Aged↗

PubMed2000

Paeonol promoted 2-aminofluorene and p-aminobenzoic acid acetylations by mononuclear leucocytes from Sprague-Dawley rats.

Following exposure of rats to the arylamine carcinogen 2-aminofluorene, DNA-carcinogen adducts were found in the target tissues of the liver and bladder, and also in circulating leucocytes. This work investigated how paeonol affects arylamine (2-aminofluorene and p-aminobenzoic acid) acetylations in rat leucocytes. Evidence is presented showing that rat mononuclear leucocytes are capable of acetylating 2-aminofluorene and p-aminobenzoic acid. Paeonol promoted 2-aminofluorene and p-aminobenzoic acid acetylation. Cultured lymphocytes produced about twice as much N-acetyl-2-aminofluorene from 2-aminofluorene and 2.2-fold as much N-acetyl-p-aminobenzoic acid from p-aminobenzoic acid as monocytes. After cotreatment with paeonol, the lymphocyte and monocyte cultures indicated that paeonol did increase 2-aminofluorene and p-aminobenzoic acid acetylations.

4-Aminobenzoic Acid↗

PubMed2000

Focus on function in geriatric assessment and rehab.

In 1994, the province of Alberta, driven by the need for deficit reduction, began a major restructuring of the provincial health care system. An integral component of this new health structure was accountability for service delivery, including the use of outcome measures to determine service effectiveness. This paper describes the efforts of one program to evaluate the effectiveness of its service delivery, in terms of functional patient outcomes, in the midst of restructuring and budget constraints.

Activities of Daily Living↗

PubMed1999

Overexpression of c-Fos enhances the transcription of human arachidonate 12-lipoxygenase in A431 cells.

The effect of transient transfection with expression vector of c-Fos on the expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. Overexpression of c-Fos increased the expression of 12-lipoxygenase mRNA and enzyme activity, and also activated the promoter activity of 12-lipoxygenase gene in a dose-dependent manner. Co-transfection with c-Fos and c-Jun expression vectors in cells synergistically increased the promoter activity of 12-lipoxygenase. With the aid of additional 5'-deletion and site-directed mutagenesis, the downstream and middle Sp1 sites residing at -123 to -114 bp and -158 to -150 bp were found to be critical for the c-Fos response of activating the transcription of human 12-lipoxygenase gene. Furthermore, the specific role of Sp1 in c-Fos response was confirmed by using the reporter plasmid driven by SV40 early promoter. These results indicate that the requirement of Sp1-binding sites in the promoter region of 12-lipoxygenase gene for c-Fos response is similar to that previously observed in EGF response.

Arachidonate 12-Lipoxygenase↗

PubMed1999

Induction of 12-lipoxygenase expression by transforming growth factor-alpha in human epidermoid carcinoma A431 cells.

Transforming growth factor-alpha (TGF-alpha) increased the expression of 12-lipoxygenase activity in a time-dependent manner in human epidermoid carcinoma A431 cells. The increase of 12-lipoxygenase activity was accompanied by an increase in 12-lipoxygenase mRNA. The effect of TGF-alpha on the promoter activation of 12-lipoxygenase gene was analyzed by using the luciferase fusion vectors. A dose-dependent effect of TGF-alpha on the reporter activity was observed, which paralleled with its effect on enzyme activity. Transient transfection with a series of 5'-deleted constructs showed that the 5'-flanking region spanning from -224 to -100 bp from translation starting site played an important role for TGF-alpha response. Site-directed mutagenesis and gel mobility shift assay indicated that two Sp1 binding sequences residing at -158 to -150 bp and 123 to -114 bp were responsible for the TGF-alpha in activation of human 12-lipoxygenase gene transcription. Expression of Sp1, but not Sp3, stimulated the promoter activity of 12-lipoxygenase in SL2 cells, indicating that the binding of Sp1 with Sp1 binding sequences played a significant role in the regulation of 12-lipoxygenase gene.

Arachidonate 12-Lipoxygenase↗

PubMed1999

The CCAAT-box binding factor NF-Y is required for the expression of phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma A431 cells.

Promoter activation in the expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene in human epidermoid carcinoma A431 cells was studied in the present investigation. Luciferase reporter assays with plasmids carrying a 400 bp of the promoter DNA were performed to analyze the regulatory element in the proximal promoter of human PHGPx gene. Transient transfection with a series of 5'-deletion and internal truncation mutants showed that the 5'-flanking region spanning from -212 to -121 bp was important for the basal expression of PHGPx gene in A431 cells. A region from -170 to -140 bp was protected in DNase I footprinting assays and bound the nuclear proteins in electrophoretic mobility shift assays. This region, denoted FP3, contains the consensus recognition sites for AP-2, CCAAT-box and CRE. The oligonucleotide competitor with the mutation at CCAAT-box could not eliminate the nuclear protein binding in gel-shift assay and the site-directed mutagenesis at the CCAAT-box decreased the luciferase activity of PHGPx promoter for approximate 50% in reporter gene assays. Competition experiments indicate that the binding of nuclear factor to the FP3 region was abolished by oligodeoxyribonucleotide corresponding to NF-Y/CP1 binding site to a greater extent than by those corresponding to sites for CTF/NFI and C/EBP. Taken together, the CCAAT-box in the promoter ranging from -156 to -151 bp, bound to NF-Y/CP1, was essential for the basal expression of human PHGPx gene in A431 cells.

CCAAT-Enhancer-Binding Proteins↗

PubMed1999

Molecular analysis of two closely related mouse aldehyde dehydrogenase genes: identification of a role for Aldh1, but not Aldh-pb, in the biosynthesis of retinoic acid.

Mammalian class I aldehyde dehydrogenase (ALDH1) has been implicated as a retinal dehydrogenase in the biosynthesis of retinoic acid, a modulator of gene expression and cell differentiation. As the first step towards studying the regulation of ALDH1 and its physiological role in the biosynthesis of retinoic acid, mouse ALDH1 cDNA and genomic clones have been characterized. During the cloning process, an additional closely related gene was also isolated and named Aldh-pb, owing to its high amino acid sequence identity (92%) with the rat phenobarbitol-inducible ALDH protein (ALDH-PB). Aldh1 spans about 45 kb in length, whereas Aldh-pb spans about 35 kb. Both genes are composed of 13 exons, and the positions of all the exon/intron boundaries are conserved with those of human ALDH1. The promoter regions of Aldh1 and Aldh-pb demonstrate high sequence similarity with those of human ALDH1 and rat ALDH-PB. Expression of Aldh1 and Aldh-pb is tissue-specific, with mRNAs for both genes being found in the liver, lung and testis, but not in the heart, spleen or muscle. Expression of Aldh-pb, but not Aldh1, was also detected at high levels in the kidney. Aldh1 and Aldh-pb encode proteins of 501 amino acids with 90% positional identity. To examine the relative roles of these two enzymes in retinoic acid synthesis in vivo, Xenopus embryos were injected with mRNAs encoding these enzymes to assay the effect on conversion of endogenous retinal into retinoic acid. Injection of ALDH1, but not ALDH-PB, mRNA stimulated retinoic acid synthesis in Xenopus embryos at the blastula stage. Thus our results indicate that Aldh1 can function in retinoic acid synthesis under physiological conditions, but that the closely related Aldh-pb does not share this property.

Aldehyde Dehydrogenase↗

PubMed1999

Cytologic features of villoglandular adenocarcinoma of the uterine cervix: comparison with typical endocervical adenocarcinoma with a villoglandular component and papillary serous carcinoma.

BACKGROUND: To the authors' knowledge, the cytologic features of villoglandular adenocarcinoma (VGC) have been described in very few publications. The malignant cells are difficult to separate from reactive glandular cells and the majority of VGCs are missed on screening cytology. METHODS: The cytologic findings of a retrospective study of four cases of pure VGC are described and are contrasted with those of papillary serous adenocarcinoma and typical mucinous endocervical adenocarcinoma with a focal component of VGC. RESULTS: Although atypical glandular cells of endocervical origin were reported when the smears from the VGC cases were examined in the screening program, none of the cases was recognized as malignant prior to histologic diagnosis. The smears showed many groups of endocervical glandular cells. Important architectural features included large cohesive groups and sheets of cells showing nuclear crowding and loss of the normal honeycomb pattern. True papillary structures comprising stromal cores covered by well polarized columnar cells with a smooth surface were characteristic. It is important to note that a "feathered edge" appearance of the cell groups was absent. The neoplastic cells were mildly atypical, showing a slight increase in the nuclear-cytoplasmic ratio but minimal hyperchromatism. The cytology smears of four cases of typical adenocarcinoma of endocervical type that had a focal VGC pattern showed cell groups with irregular borders and "feathered" edges comprised of distinctly atypical columnar cells with elongated and irregular hyperchromatic nuclei. Free-lying atypical cells and ball-like clusters of atypical cells also were present in the latter cases but not in pure VGCs. The primary high grade papillary serous adenocarcinomas of the cervix exhibited extreme cytologic atypia that was interpreted readily as malignant. CONCLUSIONS: The diagnosis of VGC on cytology smears often is missed. Papillary fragments, nuclear crowding, and subtle atypia may suggest the diagnosis.

Adenocarcinoma, Papillary↗

PubMed1999

Expression of Fas ligand in Langerhans' cell histiocytosis: A case report of a boy with multisystem involvement.

Previous reports of patients with Langerhans' cell histiocytosis have shown characteristics of osteolytic lesion, visceral involvement and organ dysfunction. We report a 2-year-old boy who was diagnosed as Langerhans' cell histiocytosis with a prominent hepatomegaly. X-Radiogram, computed tomography and magnetic resonance imaging revealed the osteolysis of the right iliac bone, the absence of the left eighth rib as well as the right mandible, and an enhancing mass in the left cerebellum. The data of radiography were highly suggestive of Langerhans' cell lineage. The presence of large CD1a-positive mononuclear cells associated with inflammatory cells in peripheral blood smear and bone marrow aspirate further confirmed the diagnosis. In addition, expressions of S100, CD25, CD68, CD80, CD86, and Fas ligand were identified on these cells by immunocytochemical staining. The results indicate that although these cells are activated Langerhans' cells, progression of the disease and the bone destruction could be mediated by the overt FasL expression of the cells.

Antigens, CD↗

PubMed1999

Uniaxial yield strains for bovine trabecular bone are isotropic and asymmetric.

Although evidence suggests that yield strains for trabecular bone are isotropic, i.e., independent of loading direction, decisive support for this hypothesis has remained elusive. To explicitly test whether yield strains for trabecular bone are isotropic, compressive and tensile yield strains of 51 specimens of bovine tibial trabecular bone (0.41 +/- 0.08 g/cm3 [mean apparent density +/- SD]) were measured without end artifacts in on-axis (along the principal trabecular orientation) and off-axis (30-40 degrees oblique to on-axis) orientations. Yield strains for the on-axis and off-axis orientations were similar in tension (0.80 +/- 0.03% compared with 0.85 +/- 0.04%, p = 0.21) and compression (0.97 +/- 0.05% compared with 0.96 +/- 0.07%, p > 0.99); as expected, modulus and strength depended on loading direction. When considered with an ancillary experiment on bovine tibial trabecular bone that showed yield strains to be similar between on-axis and 90 degrees off-axis bone, these results firmly establish the isotropy of uniaxial yield strains for bovine tibial trabecular bone. This bone is of high density and has a strong, plate-type, anisotropic architecture. Therefore, yield strains for uniaxial loading are expected to be isotropic, or nearly so, for other types of dense trabecular bone, although further work is required to confirm this and to establish this behavior for bone of lower density.

Animals↗

PubMed1999

Inhibitory effect of phospholipid hydroperoxide glutathione peroxidase on the activity of lipoxygenases and cyclooxygenases.

The partially purified phospholipid hydroperoxide glutathione peroxidase (PHGPx) from A431 cells was used to systematically compare the inhibitory effect on the enzyme activity of various lipoxygenases and cyclooxygenases. Under the standard assay system, platelet 12-lipoxygenase, 15-lipoxygenase, and cyclooxygenase-2 were the most sensitive to the inhibition by PHGPx. 5-Lipoxygenase and cyclooxygenase-1 were less sensitive to the inhibition by PHGPx than platelet 12-lipoxygenase and cyclooxygenase-2, respectively, and the difference was approximately 10-fold. Reduction of 12(S)-hydroperoxyeicosatetraenoic acid to 12(S)-hydroxyeicosatetraenoic acid by PHGPx was observed in the presence of glutathione (GSH), and the inhibitory effect of PHGPx on 12-lipoxygenase-catalyzed arachidonate metabolism was reversed by the addition of exogenous lipid hydroperoxide. The results indicate that PHGPx directly reduced lipid hydroperoxides and then down-regulated the activity of arachidonate oxygenases. Moreover, a high-level expression of PHGPx mRNA and its 12-lipoxygenase-inhibitory activity was observed in cancer cells and endothelial cells, and these results suggest that PHGPx may play a significant role in the regulation of reactive oxygen species formation in these cells.

Animals↗