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C S Yang

Publications and source records attributed to C S Yang.

At least 145 records · Page 8Linked to original sources
PubMed1997

A hypothetical model for the active site of human cytochrome P4502E1.

1. A model for the active site structure of human cytochrome P4502E1 based on the coordinates of cytochrome P450BM-3 crystal structure and the sequence analysis information on P4502E1 was proposed. 2. The sequence alignment of mammalian P4502 family and P450BM-3 indicated a 48%, similarity and 25% identity. Secondary structural prediction displayed a similar pattern of distribution in the main frame of secondary elements, alpha-helices and beta-sheets. The locations of secondary elements also mapped well. In addition, the amino acids responsible for the conserved secondary structural regions showed the most similarity between the two proteins. In contrast, the amino acids responsible for the loop region had the least similarity in our alignment. 3. The predicted P4502E1 active site model shows that the active site is small and contains mainly hydrophobic residues. The substrate binding pocket is located on top of pyrrole rings A and D of the haen; in contrast, the access to B and C rings is partially or completely blocked by protein side chains. 4. Residues within possible contact of a representative substrate, N-nitrosodimethylamine, are He115, Ala299, Thr303, Val364 and possibly He469.

Amino Acid Sequence↗
PubMed1997

Inhibition of carcinogenesis by tea: the evidence from experimental studies.

In its various forms, tea is one of the most widely consumed beverages in the world. Elucidation of the chemical components of tea has revealed that the beverage is a rich repository of antioxidants. Among these are the polyphenolics, common to green tea, but also found in black teas together with oxidized polymers that in part account, for the darkened color. Consumption of tea on a regular basis has been associated with reduced risk of several forms of cancer in human populations, with the strongest evidence linking green tea use to reduction in cancer risk in parts of Asia. To understand how tea prevents cancer, studies in animal carcinogenesis models have been done with very encouraging results. This review examines the available data from animal studies on the effects of tea in the prevention of cancer.

Animals↗
PubMed1997

Chemopreventive activity of thiol conjugates of isothiocyanates for lung tumorigenesis.

A series of L-cysteine (L-Cys), glutathione (GSH), and N-acetyl-L-cysteine (NAC) conjugates of phenethyl (PEITC), benzyl (BITC), and 6-phenylhexyl isothiocyanate (PHITC) were studied for their inhibitory activity toward metabolic activation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mouse lung microsomes. Selected compounds, PEITC, PEITC-GSH, PEITC-NAC and PHITC-NAC, were also assayed for the potential chemopreventive activity toward NNK-induced lung tumorigenesis in A/J mice. Results showed that PEITC and its conjugates inhibited NNK metabolism with decreasing potency: PEITC < PEITC-GSH > PEITC-Cys > PEITC-NAC. PHITC and its GSH and NAC conjugates exhibited nearly 10 times higher inhibitory activity toward NNK metabolism than the PEITC counterparts. In the tumor bioassay, as expected, the conjugates exhibited inhibitory activity against lung tumorigenesis induced by NNK. PEITC-GSH was not inhibitory at 4 micromol/mouse, but it inhibited approximately 32% of lung tumor multiplicity at 8 micromol/mouse. PEITC-NAC at 5 and 20 micromol/mouse both inhibited approximately 30% tumor multiplicity. Among all the conjugates examined, PHITC-NAC was the most potent. At a 5-micromol dose, it completely inhibited tumor multiplicity and incidence to the background level observed in the control group. These results revealed that the structure-activity relationships of the conjugates are similar to those found with their parent isothiocyanates (ITCs), i.e., the potency increased with the increasing alkyl chain length from two to six carbons in arylalkyl ITCs, suggesting that a common active species is involved. The inhibitory activity of ITC conjugates and the expected low toxicity make thiol conjugates of ITC a promising new series of chemopreventive agents.

Animals↗
PubMed1997

Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen.

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.

Adenocarcinoma↗
PubMed1997

Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice.

The present study investigated the inhibitory activity against lung tumorigenesis by a group of characteristic black tea polyphenols, theaflavins. In a short-term study, female A/J mice were treated with a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 103 mg/kg b.w., i.p.) on day 0, and 0.1 and 0.3% theaflavins were administered as the sole source of drinking fluid starting 24 h after NNK treatment. The proliferation index of the lung tissues was measured by the incorporation of bromodeoxyuridine (BrdU) immunohistochemically. The highest NNK-induced proliferation rate of bronchiolar cells, observed on day 5, was significantly decreased by 0.3% theaflavins (proliferation index, 1.51 +/- 0.08 versus 2.35 +/- 0.16). In a long-term lung tumorigenesis study, pulmonary adenomas were observed in 100% (30/30) of the mice at week 16 after NNK treatment. Administration of theaflavins (0.1%) as the sole source of drinking fluid, starting 2 days after the NNK treatment until the termination of the experiment, significantly reduced the tumor multiplicity and volume by 23% (8.5 +/- 0.6 versus 6.5 +/- 0.6 tumors/mouse) and 34% (0.08 versus 0.05 mm3 per tumor), respectively. The proliferation index in lung adenomas was also significantly inhibited by theaflavins. The present work demonstrates the inhibitory action of theaflavins against NNK-induced pulmonary hyperproliferation and tumorigenesis.

Animals↗
PubMed1997

Enzymes involved in the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in patas monkey lung and liver microsomes.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific carcinogen in animals. Our previous studies indicated that there are differences between rodents and humans for the enzymes involved in the activation of NNK. To determine if the patas monkey is a better animal model for the activation of NNK in humans, we investigated the metabolism of NNK in patas monkey lung and liver microsomes and characterized the enzymes involved in the activation. In lung microsomes, the formation of 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide), 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was observed, displaying apparent Km values of 10.3, 5.4, 4.9, and 902 microM, respectively. NNK metabolism in liver microsomes resulted in the formation of keto aldehyde, keto alcohol, and NNAL, displaying apparent Km values of 8.1, 8.2, and 474 microM, respectively. The low Km values for NNK oxidation in the patas monkey lung and liver microsomes are different from those in human lung and liver microsomes showing Km values of 400-653 microM, although loss of low Km forms from human tissue as a result of disease, surgery or anesthesia cannot be ruled out. Carbon monoxide (90%) significantly inhibited NNK metabolism in the patas monkey lung and liver microsomes by 38-66% and 82-91%, respectively. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) and aspirin (a cyclooxygenase inhibitor) decreased the rate of formation of keto aldehyde and keto alcohol by 10-20 % in the monkey lung microsomes. Alpha-Napthoflavone and coumarin markedly decreased the oxidation of NNK in monkey lung and liver microsomes, suggesting the involvement of P450s 1A and 2A6. An antibody against human P450 2A6 decreased the oxidation of NNK by 12-16% and 22-24% in the patas monkey lung and liver microsomes, respectively. These results are comparable to that obtained with human lung and liver microsomes. Coumarin hydroxylation was observed in the patas monkey lung and liver microsomes at a rate of 16 and 4000 pmol/min/mg protein, respectively, which was 5-fold higher than human lung and liver microsomes, respectively. Immunoblot analysis demonstrated that the P450 2A level in the individual patas monkey liver microsomal sample was 6-fold greater than in an individual human liver microsomal sample. Phenethyl isothiocyanate, an inhibitor of NNK activation in rodents and humans, decreased NNK oxidation in the monkey lung and liver microsomes displaying inhibitor concentration resulting in 50% inhibition of the activity (IC50) values of 0.28-0.8 microM and 4.2-6.8 microM, respectively. The results demonstrate the similarities and differences between species in the metabolic activation of NNK. The patas monkey microsomes appear to more closely resemble human microsomes than mouse or rat enzymes and may better reflect the activation of NNK in humans.

Animals↗
PubMed1997

Evidence for cytochrome P450 2A6 and 3A4 as major catalysts for N'-nitrosonornicotine alpha-hydroxylation by human liver microsomes.

The tobacco specific carcinogen N'-nitrosonornicotine (NNN), is believed to be a causative agent for esophageal cancer in smokers. NNN requires metabolic activation to exert its carcinogenic potential. Metabolism occurs through cytochrome P450 (P450) catalyzed 2'- and 5'-hydroxylation, which generates unstable metabolites that decompose to 4-hydroxy-1-(3-pyridyl)-1-butanone ('keto alcohol') and 4-hydroxy-4-(3-pyridyl)butanal, respectively. The latter cyclyzes to 5-(3-pyridyl)-2-hydroxytetrahydrofuran ('lactol'). 2'-Hydroxylation of NNN is believed to be the pathway critical for esophogeal NNN carcinogenesis in the rat. The ability of human liver microsomes and expressed human P450s to metabolize [5-(3)H]NNN to keto alcohol and lactol was determined by reverse phase HPLC with radioflow detection. At low NNN concentrations, 11 human liver microsomes metabolized NNN primarily by 5'-hydroxylation to lactol. This reaction was strongly correlated (r = 0.92) with coumarin 7-hydroxylation, suggesting that NNN 5'-hydroxylation is catalyzed mainly by P450 2A6. 2'-Hydroxylation of NNN by human liver microsomes correlated with 6beta-hydroxylation of testosterone, a P450 3A4-specific activity (r = 0.94). The relative rates of 2'- and 5'-hydroxylation by human P450s 2A6, 2E1, 2D6 and 3A4 expressed in Sf9 cells by the baculovirus-insect cell expression system, and human P450 3A4 produced by stable expression in Chinese hamster ovary cells, were determined. Human P450 2A6 metabolized 1 microM NNN exclusively by 5'-hydroxylation. The rate of lactol formation was 317 pmol/min per nmol P450. Human P450s 2E1 and 2D6 also metabolized NNN only to lactol, but at much lower rates, 0.4 and 0.8 pmol/min per nmol of P450 respectively. In contrast, the metabolism of NNN by expressed human P450 3A4 was specific for keto alcohol formation. The Km for 5'-hydroxylation by baculovirus-expressed P450 2A6 was 2.1 microM, and k(cat) was 953 pmol/min per nmol of P450. The Km for lactol formation by human liver microsomes containing high levels of P450 2A6, was 5 microM . Human liver microsomes exhibited a Km of 312 microM for keto alcohol formation. Coumarin, 8-methoxypsoralen (P450 2A6 inhibitors), and anti-2A6 monoclonal antibody were strong inhibitors of NNN-derived lactol formation in human liver microsomes. Troleandomycin, an inhibitor of P450 3A4, effectively inhibited the metabolism of NNN to keto alcohol by human liver microsomes. These results are consistent with P450 2A6 mediated 5'-hydroxylation and P450 3A4 mediated 2'-hydroxylation of NNN in human liver microsomes.

Animals↗
PubMed1997

Development of a human lymphoblastoid cell line constitutively expressing human CYP1B1 cDNA: substrate specificity with model substrates and promutagens.

An AHH-1 TK+/- cell derivative was developed that stably expresses human cytochrome P4501B1 (CYP1B1) cDNA in an extrachromosomal vector which confers resistance to 1-histidinol and co-expresses NADPH cytochrome P450 oxidoreductase (OR). The CYP1B1-expressing cell line was designated h1B1/OR. Microsomes prepared from CYP1B1 cDNA expressing cells exhibit elevated levels of 7-ethoxy-resorufin deethylase (EROD), 7-ethoxy-4-trifluoromethyl-coumarin deethylase (EFCD), benzo(alpha)pyrene hydroxylase (BPH), bufuralol 1'-hydroxylase, testosterone hydroxylase activities and spectrally quantifiable cytochrome P450. CYP1B1-containing microsomes did not contain detectable coumarin 7-hydroxylase, p-nitrophenol hydroxylase, lauric acid hydroxylase, (S)-mephenytoin 4'-hydroxylase or diclofenac 4'-hydroxylase activities. Kinetic parameters for selected substrates were compared among CYP1B1 and the two additional members of the CYP1 family, CYP1A1 and CYP1A2. For BPH and EFCD, the rank order of rates of substrate metabolism were CYP1A1 > CYP1B1 > CYP1A2. For EROD, the rank order of substrate metabolism was CYP1A1 > CYP1A2 > CYP1B1. For both EROD and EFCD the apparent K(m) values for CYP1B1 were more similar to CYP1A1 than to CYP1A2. In order to begin to characterize the promutagen activating ability of CYP1B1, the mutagenicity of selected chemicals was examined in h1B1/OR cells; there was increased sensitivity (CYP1B1-expressing relative to control cells) to the mutagenicity of benzo(a)pyrene, cyclopenta(c,d)pyrene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and aflatoxin B1 (AFB). CYP1B1, expressed in this system, appears to be particularly efficient at activating AFB.

Aflatoxin B1↗
PubMed1997

Cooperative interaction between Bcl-2 and Epstein-Barr virus latent membrane protein 1 in the growth transformation of human epithelial cells.

The Epstein-Barr virus latent membrane protein 1 (LMP-1) is essential for virus-induced B cell immortalization and can protect B lymphoma cell lines from apoptosis signals in vitro via induction of cellular Bcl-2 expression. However, we have reported that high-level expression of LMP-1 in epithelial cells (RHEK-1 cells) itself induces apoptosis. This apoptotic event occurs in the absence of detectable Bcl-2 expression in the LMP-1-transfected epithelial cells. In this study, we transfected the bcl-2 gene into the LMP-1-containing cells and examined the effect of Bcl-2 upon LMP-1-mediated apoptosis, and upon the growth phenotype of the transfected cells. The results show that ectopic expression of Bcl-2 specifically blocks apoptotic death induced by LMP-1. This was observed from cell culture viability and from gel electrophoresis and flow cytometric assays of the degree of DNA fragmentation in cultured cells. Furthermore, co-expression of LMP-1 and Bcl-2 in RHEK-1 cells enabled the cells to grow under low-serum conditions and to form colonies in semi-soft agar medium. These results suggest, therefore, that these two proteins play important complementary roles in the process of EBV-associated epithelial cell transformation. It appears significant, therefore, that LMP-1 and Bcl-2 are frequently co-expressed in the malignant cells of an EBV-positive epithelial tumour, nasopharyngeal carcinoma.

Cell Division↗
PubMed1997

Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans.

Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects.

Adolescent↗
PubMed1997

Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen.

We examined the full-length hepatitis B virus (HBV) envelope (surface antigen or HBV small surface antigen [HBsAg]) sequences of 12 different liver samples from 10 different hepatoma-containing chronic carriers. Surprisingly, novel and frequent mutations occurred predominantly at amino acids 40 and 47 of HBsAg, in addition to within a known protective B-cell epitope (so-called group a determinant of HBsAg 124-148). Approximately 58% of chronic carriers contain mutations at the group a determinant. The mutation frequency at the hotspot codons 40 and 47 is approximately 83%, 1 order of magnitude higher than at the known polymorphic sites of subtype-specific determinants at codons 122 and 160, which is approximately 4%. This new mutational domain is found to coincide with a major histocompatibility complex class I-restricted T-cell epitope. The potential biological significance of this novel mutation in the immunopathogenesis of HBV chronic carriers is discussed.

Adult↗
PubMed1997

Genetic polymorphism of cytochrome P450 as a biomarker of susceptibility to environmental toxicity.

Cytochrome P450 (CYP) enzymes are responsible for the metabolism of numerous xenobiotics and endogenous compounds, including the metabolic activation of most environmental toxic chemicals and carcinogens. Both metabolic and genetic polymorphisms have been identified for human CYP enzymes. The association of CYP genetic polymorphism and human cancer risk, and susceptibility to environmental hazards, have received increasing attention. This article briefly reviews the approaches and methods currently used in CYP genetic polymorphism studies. In addition, the current status and perspectives of using CYP genetic polymorphism as a biomarker of individual susceptibility to cancer and environmental toxicity are discussed.

Biomarkers↗
PubMed1997

Polyphenols as inhibitors of carcinogenesis.

Many polyphenolic compounds have demonstrated anticarcinogenic activities in animal models. These compounds include flavanone, flavonols, isoflavone, and catechins. In this article, tea catechins will be used as an example to illustrate current research in this area. Many laboratory studies have demonstrated the inhibition of tumorigenesis in animal models by different tea preparations. The animal models include tumorigenesis in the mouse lung, rat and mouse esophagi, mouse forestomach, mouse skin, mouse duodenum, rat small intestine, rat and mouse livers, and rat colon. In most of the studies, the inhibitory activity of tea could be demonstrated when tea preparations were given either during or after the carcinogen treatment period. Black tea was also effective, although the activity was weaker than green tea in some experiments. Decaffeinated tea preparations were also active in many model systems. The molecular mechanisms for these broad inhibitory actions are not fully understood. They are most likely related to the biochemical actions of the tea polyphenols, which include antioxidative activities and inhibition of cell proliferation and of tumor promotion-related activities. The effect of tea consumption on human cancers is not clear in spite of numerous investigations. The bioavailability and pharmacokinetics of tea polyphenols are being studied in animals and humans to provide a basis for more quantitative analyses on the effect of tea on carcinogenesis. More mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

Animals↗
PubMed1997

Molecular subtyping of human T-lymphotropic virus type I (HTLV-I) by a nested polymerase chain reaction-restriction fragment length polymorphism analysis of the envelope gene: two distinct lineages of HTLV-I in Taiwan.

The major type of human T-lymphotropic virus type I (HTLV-I), generally referred to as the cosmopolitan type, has been grouped into three subtypes (A, B, and C) by phylogenetic analysis of the long terminal repeat sequences of the viral genome. Twelve subtype-specific nucleotide variations have been deduced by comparison between the envelope (env) sequences of 16 HTLV-I strains with defined subtypes and 9 Taiwanese HTLV-I strains. To gain further insights into the molecular epidemiology of HTLV-I and the origin of this virus in Taiwan, a rapid method of identification for the cosmopolitan subtypes was developed by using a nested polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) studies using the two subtype B-specific and four subtype C-specific nucleotides located within the positions 5708 to 6320 of the envgene. The nested PCR-RFLP method was used to subtype HTLV-I from four virus-positive cell lines derived from 1 Japanese and 3 North American patients, as well as 41 blood-unrelated Taiwan Chinese. The sequences of PCR products were determined and the six positions of subtype-specific nucleotide variations were examined. The sequence data completely supported the subtyping data via the nested PCR-RFLP method. The results demonstrated that, as is the case in Japan, at least two distinct cosmopolitan subtypes (A and B) of HTLV-I were present in Taiwan, but the more prevalent subtype in Taiwan is A in contrast to subtype B in Japan. Furthermore, rapid subtyping could facilitate molecular epidemiological studies of HTLV-I infection and linkage between HTLV-I subtypes and virus-associated diseases.

Base Sequence↗
PubMed1997

A crossover comparison of intermittent oral and intravenous administration of calcitriol on the parathyroid hormone concentration in hemodialysis patients.

Active vitamin D3 is used commonly in hemodialysis patients with severe secondary hyperparathyroidism. Intermittent pulse therapy with active vitamin D3, either orally or intravenously, has been proven to be effective with less hypercalcemic complication than daily oral vitamin D3. We therefore designed a three-phase crossover study to compare the effect of oral and intravenous calcitriol given by intermittent pulse therapy. Thirteen regular hemodialysis patients were enrolled. In phase 1, 1 microgram calcitriol was given orally at bedtime twice a week for 4 months, and then was stopped for 1 month to washout. In phase 2, 1 microgram calcitriol was given intravenously immediately after hemodialysis twice a week for 2 months, and then was stopped for 1 month to washout. Phase 3 repeated phase 1 but lasted for only 2 months. Calcium carbonate was given as the sole phosphate-binding agent if there was no severe hypercalcemia or hyperphosphatemia. Serum parathyroid hormone (PTH) levels decreased dramatically in all three phase therapies. As a result, mid-molecule PTH decreased from 5.71 +/- 2.65 to 3.97 +/- 2.92 ng/ml in phase 1 (p = 0.010), from 4.34 +/- 3.39 to 1.98 +/- 1.76 ng/ml in phase 2 (p = 0.007), and from 2.72 +/- 0.97 to 1.67 +/- 0.71 ng/ml in phase 3 (p = < 0.001). However, there was no difference in the calculation of the PTH declination among the three phases (32, 50 and 42%, respectively). The incidence of hypercalcemia was higher in using calcitriol than without it (23 vs. 6%, p < 0.05), but there was no difference between intravenous and oral calcitriol (35 vs. 19%). The above results suggested that both oral and intravenous calcitriol, with lower doses and intermittent pulse therapy, were equally effective in controlling secondary hyperparathyroidism. The incidences of hypercalcemia were similar in both oral and intravenous calcitriol using 3.5 mEq/1 dialysate calcium concentration and calcium carbonate as the chief phosphate binder.

Administration, Oral↗
PubMed1997

Evaluation of multiple antibodies to Epstein-Barr virus as markers for detecting patients with nasopharyngeal carcinoma.

Five serological tests were assessed for their sensitivity for screening and early detection of nasopharyngeal carcinoma (NPC). The tests included the detection of antibodies to various gene products of EBV: viral capsid antigen (VCA) using an indirect immunofluorescence assay (FA), DNase using an activity neutralisation test (NT), Dnase using an enzyme-linked immunosorbent assay (ELISA), DNA polymerase (DP) using NT, and major DNA binding protein (MDBP) by ELISA. Sera from 100 NPC outpatients and 20 NPC patients, who were detected in a prospective study, were examined. The results showed that levels of antibody to DNase detected by ELISA and to DP detected by NT and the positivity rate for VCA by FA increased with NPC stage. More species of EBV antibody became detectable as NPC progressed. The detection of anti-MDBP antibody by ELISA was suitable for screening for NPC. Anti-DP antibody detected by NT was a valuable marker both for early detection and prognosis of NPC. Detection of anti-DNase antibody by ELISA was the most sensitive method for detection of NPC. No single test was sufficient to detect all the NPC patients and a combination of anti-DNase by ELISA with other tests are recommended to identify NPC patients.

Antibodies, Viral↗
PubMed1997

Absorption, distribution, elimination of tea polyphenols in rats.

Tea polyphenols-including (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC)-are believed to be responsible for the beneficial effects of tea. This study was conducted to investigate the absorption, distribution, and elimination of EGCG, EGC, and EC in rats after administration of decaffeinated green tea (DGT). For comparison, pure EGCG was also studied. The plasma and tissue levels of EGCG, EGC, and EC were quantified by HPLC, and the results were analyzed by the PCNONLIN program. Following intravenous injection of DGT (25 mg/kg), the plasma concentration-time curves of EGCG, EGC, and EC were fitted in a two-compartment model. The beta-elimination half-lives (t1/2beta) were 212, 45, and 41 min for EGCG, EGC, and EC, respectively; the clearances were 2.0, 7.0, and 13.9 ml x min/kg, and the apparent distribution volumes (V(d)) were 1.5, 2.1, and 3.6 dl/kg. When pure EGCG (10 mg/kg) was given, however, a shorter t1/2beta (135 min), a larger clearance (72.5 ml x min/kg), and a larger V(d) (22.5 dl/kg) for EGCG were observed, suggesting that other components in DGT could affect the plasma concentration and elimination of EGCG. After intragastric administration of DGT (200 mg/kg), approximately 13.7% of EGC and 31.2% of EC were shown in the plasma, but only 0.1% of EGCG was bioavailable as judged by the ratio of AUC(i.g.)/AUC(i.v.). After intravenous administration of DGT (25 mg/kg), the level of EGCG was found to be the highest in the intestine samples, and the intestinal EGCG level declined with a t1/2 of 173 min. The highest levels of EGC and EC were observed in the kidney, and the levels declined rapidly with t1/2 of 29 and 28 min, respectively. The AUC of EGCG in the intestine was 4-fold higher than that in the kidney, but the AUCs of EGC and EC in the intestine were similar to those in the kidney. The liver and lung levels of EGCG, EGC, and EC were generally lower than those in the intestine and the kidney. The distribution results suggest that EGCG is mainly excreted through bile, and that EGC and EC are excreted through both the bile and urine.

Administration, Oral↗