Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 253 records · Page 14Linked to original sources

PubMed1993

Tea and cancer.

Tea is one of the most popular beverages consumed worldwide. The relationship between tea consumption and human cancer incidence is an important concern. This topic has been studied in different populations by many investigators, but no clear-cut conclusion can be drawn. Whereas some studies have shown a protective effect of tea consumption against certain types of cancers, other studies have indicated an opposite effect. Our purpose is to provide a critical review of this topic, covering basic chemistry and biochemical activity of tea, epidemiologic investigations, and laboratory studies, as well as possible directions for future research. Studies have demonstrated either a lack of association between tea consumption and cancer incidence at specific organ sites or inconsistent results. On the other hand, many laboratory studies have demonstrated inhibitory effects of tea preparations and tea polyphenols against tumor formation and growth. This inhibitory activity is believed to be mainly due to the antioxidative and possible antiproliferative effects of polyphenolic compounds in green and black tea. These polyphenolics may also inhibit carcinogenesis by blocking the endogenous formation of N-nitroso compounds, suppressing the activation of carcinogens, and trapping of genotoxic agents. The effect of tea consumption on cancer is likely to depend on the causative factors of the specific cancer. Therefore, a protective effect observed on a certain cancer with a specific population may not be observable with a cancer of a different etiology. On the basis of this concept, we suggest future laboratory and epidemiologic studies to elucidate the relationship between tea consumption and human cancer risk.

Animals↗

PubMed1993

Regulation of cytochrome P450 2B1/2 genes by diallyl sulfone, disulfiram, and other organosulfur compounds in primary cultures of rat hepatocytes.

Our previous study demonstrated that diallyl sulfide (DAS), a compound derived from garlic, transcriptionally activated the P450 2B1/2 genes in rat liver. In the present study, rat primary hepatocytes were used to determine the effects of DAS and its metabolite, diallyl sulfone (DASO2), on the expression of the P450 2B1/2 genes. Freshly isolated adult rat hepatocytes were cultured in a serum-free medium on a reconstituted basement membrane matrix "matrigel" that enabled the hepatocytes to maintain expression of numerous liver-specific genes for more than 1 week. After 48-hr of acclimation, 0.1, 0.5, and 2.0 mM concentrations of DAS or DASO2 were added to the culture medium and the cells were harvested at 4, 12, 24, or 36 hr after the treatment for the preparation of microsomes and RNA. Cytotoxicity was not observed by morphological examinations after DAS and DASO2 treatments. In contrast to the in vivo results, there was only a slight increase in the levels of P450 2B1/2 mRNA and protein in DAS-treated cells. However, DASO2 treatment (2 mM) resulted in 11-, 21-, and 22-fold increases in P450 2B1/2 mRNA levels at 12, 24, and 36 hr after the treatment, respectively. P450 2B1/2 protein levels were also increased markedly in DASO2-treated cells. Co-incubation of the rat hepatocyte cultures with a physiological concentration of growth hormone significantly blocked the induction of P450 2B1/2 mRNA by DASO2. Northern blot analysis using oligonucleotide probes specific for 2B1 and 2B2 demonstrated that DASO2 induced mRNA levels of both 2B1 and 2B2, with a greater induction of 2B1 mRNA. For comparison, the effects of disulfiram (DSF) and its metabolite, diethyldithiocarbamate (DDTC), on P450 2B1/2 mRNA expression were also examined in the cultured rat hepatocytes. Both DSF and DDTC caused a significant increase in P450 2B1/2 mRNA level with the highest induction at 0.5 mM. Addition of growth hormone to the culture effectively suppressed the P450 2B1/2 mRNA induction by DSF but had little effect on the induction by DDTC. Neither mRNA nor protein levels of P450 2E1 in cultured hepatocytes were affected by all the organosulfur compounds tested. These results suggest that DASO2, DSF and DDTC selectively modulate P450 isozymes in cultured rat primary hepatocytes and that the induction of P450 2B1/2 by DAS in rat liver may be mediated by its metabolite, DASO2.

Allyl Compounds↗

PubMed1993

Accumulation of p53 protein in human esophageal precancerous lesions: a possible early biomarker for carcinogenesis.

The level of p53 protein was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, dysplasia, carcinoma in situ, and carcinoma) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linxian and Huixian in the Henan province). Tissue sections were incubated with p53 antibodies for immunostaining. Conventional hematoxylin and eosin stain was also used. In surgically resected esophageal specimens, elevated p53 protein levels were found in the cell nuclei in tissues with precancerous and cancerous lesions. From basal cell hyperplasia to dysplasia to carcinoma in situ, the p53 immunostain-positive cells increased in number, and their distribution had roughly the same pattern as that of the proliferating cells. However, positive stain was not observed in the dividing basal cells of the normal epithelium of the surgically resected tissues. A similar pattern of immunostaining was observed in the abnormal tissues of the biopsy samples from the symptom-free subjects. An intriguing observation is that some p53 immunostain-positive cells were observed in 3 of 6 cases of histologically normal epithelia of biopsy samples. Only the papillary immunostaining pattern was observed in these three "normal" cases. Although the molecular basis for such positive stain remains to be investigated, it is possible that p53 protein accumulation occurs early in the pathogenesis of esophageal cancer and that p53 mutation is closely associated with the initiation of this cancer. The accumulation of p53 protein may be a promising early biomarker for identifying high-risk subjects for esophageal cancer.

Adult↗

PubMed1993

Transcriptional activation of cytochrome P450 2B1/2 genes in rat liver by diallyl sulfide, a compound derived from garlic.

Previous work in our laboratory demonstrated that cytochrome P450 2B1 in rat liver was induced, but P450 2E1 was inhibited and inactivated, by diallyl sulfide (DAS), a compound derived from garlic. Such a selective effect on P450 enzymes is of considerable interest toward the understanding of dietary effects on xenobiotic metabolism. In the present study, the mechanism of P450 2B1 induction by DAS was investigated. Following a single dose of DAS (200 mg/kg body weight, ig), liver microsomal pentoxyresorufin dealkylase (PORd) activity, a representative activity of P450 2B1, was induced 3-, 16-, 26-, and 43-fold at 6, 12, 18, and 24 h after the treatment, respectively. A corresponding increase in the level of P450 2B1/2 protein was observed by immunoblot analysis. The level of P450 2B1/2 mRNA in rat liver also increased markedly, reaching a maximum at 12 h after the DAS treatment. Hybridization with the isozyme-specific oligonucleotide probes revealed that the mRNA levels of both P450s 2B1 and 2B2 were induced. In contrast, the level of P450 2E1 mRNA in the liver of DAS-treated rats was not changed. The results of nuclear run-on assay revealed that the transcriptional rate of P450 2B1/2 genes in the rat liver increased 13-fold at 6 h after DAS administration and returned to the control value at 24 h. The transcription of P450 2B1/2 genes was blocked completely by alpha-amanitin, an inhibitor of RNA polymerase II. These results clearly demonstrate that the induction of P450 2B1/2 in rat liver by DAS is mainly due to transcriptional activation. In the DAS-treated rats, P450 2B1/2 mRNA was also markedly induced in the stomach and duodenum. The maximal induction was found at 12 h after the treatment while the levels of P450 2B1/2 mRNA increased 66-fold in the duodenum and 23-fold in the stomach. DAS treatment, however, did not change the levels of P450 2B1/2 mRNA in the lung and nasal mucosa.

Allyl Compounds↗

PubMed1993

Sex-related differences in mouse renal metabolism and toxicity of acetaminophen.

The objective of this study is to elucidate the role of cytochrome P450 2E1 in the metabolic activation of acetaminophen (APAP) in mouse kidneys. With the kidney microsomes from C3H/HeJ mice, a significant sex-related difference was observed in the NADPH-dependent formation of a reactive APAP metabolite which was trapped as a glutathione conjugate. The enzyme activity in male mouse kidney was about 35- and 50-fold higher than that in the females at substrate concentrations 50 and 500 microM, respectively, and treatment of female mice with testosterone significantly induced the enzyme activity in the mouse kidney. No sex-related difference in this enzyme activity, however, was observed in the livers. The oxidative metabolism of APAP in control male mouse kidney microsomes displayed an apparent low Km of 43-45 microM and an apparent high Km of 603-702 microM. Studies using monoclonal antibodies against P450 2E1 showed that P450 2E1 accounted for about half of the activity in the metabolic activation of APAP in both mouse liver and kidney. Furthermore, there was as strong correlation between the renal P450 2E1 content (measured by Western blot analysis) and the rate of APAP oxidation by renal microsomes. To test the hypothesis that the susceptibility of renal tissue to APAP toxicity is determined by the distribution and level of P450 2E1, toxicity studies were conducted. A time-dependent depletion of hepatic and renal cortical glutathione was observed in both male and female mice following a dose of 1200 mg/kg APAP. At 4 hr after APAP dosing, the level of renal cortical glutathione depletion in male mice was significantly greater than that in the females. The level of blood creatinine elevation in male mice was higher than that in the females 8 hr after APAP dosing. Histopathology studies by light and electron microscopic assessments demonstrated that renal damage by APAP was restricted mostly to the epithelial cells of the proximal convoluted tubules where P450 2E1 was localized. The renal proximal tubular necrosis induced by APAP was more severe in males than that in the females. Results from this study suggest that P450 2E1 plays an important role in the metabolic activation of APAP and is a key factor in determining the sex-related difference of APAP-mediated toxicity in the mouse kidney.

Acetaminophen↗

PubMed1993

Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5, microsomal epoxide hydrolase, and glutathione transferases: evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquinone.

Benzene metabolism was investigated using two purified rat hepatic MFO systems containing either cytochrome P450 2B1 or cytochrome P450 2E1. Studies performed over a wide substrate concentration range indicate that cytochrome P450 2B1 represents a relatively low-affinity form of cytochrome P450 with respect to benzene metabolism while cytochrome P450 2E1 is substantially more efficient at low benzene concentrations (apparent Km value 0.17 mM). Cytochrome b5 stimulated benzene metabolism by both cytochromes P450 2B1 and P450 2E1. With cytochrome P450 2E1 the stimulation of benzene metabolism by cytochrome b5 was very pronounced (up to 6-fold) at low concentrations of benzene and was most effective (up to 15-fold) with respect to formation of hydroquinone. The metabolites observed in these studies were phenol and hydroquinone. Cytochrome P450 2E1 metabolized phenol with an affinity and capacity comparable to those of benzene. Hydroquinone was the major product formed at all substrate concentrations, while some catechol was formed at all substrate concentrations, while some catechol was formed at higher concentrations of phenol. Phenol metabolism was also stimulated by cytochrome b5. The metabolism of benzene by cytochrome P450 2E1 in the presence of the major microsomal epoxide hydrolase, mEHb, yielded phenol, hydroquinone, and benzene dihydrodiol. Interestingly, the addition of mEHb did not lead to a decrease of the toxicologically important metabolite hydroquinone as might be expected from sequestration of the intermediate benzene oxide to the vicinal dihydrodiol pathway but rather led to a marked (more than 4-fold) increase in the formation of hydroquinone, suggesting catalysis by mEHb of a predominant attack at the homoallylic position rather than at a carbon atom which forms the epoxide ring of benzene oxide. The addition of glutathione transferases plus glutathione did not yield GSH conjugates during benzene metabolism. However, metabolism of phenol by cytochrome P450 2E1 in the presence of glutathione yielded a nonenzymatically formed glutathione conjugate derived from hydroquinone or from an oxidative product of hydroquinone.

Animals↗

PubMed1993

Use of bacterially-expressed antigen for detection of antibodies to the EBV-specific deoxyribonuclease in sera from patients with nasopharyngeal carcinoma.

A cDNA clone, BG9, corresponding to the open reading frame BGLF5 of Epstein-Barr virus (EBV) DNase was inserted into an E. coli expression vector, pET3a, to generate a recombinant plasmid, pDNase 5. High level of expression of a DNase activity was detected in the E. coli transformed with pDNase 5 following induction with IPTG. The enzyme activity was purified using DEAE-cellulose, phosphocellulose and DNA-cellulose column chromatography. The purified protein appeared to be nearly homogeneous in SDS-PAGE using Coomassie blue staining. The requirement for divalent cations and optimum pH as well as inhibitory concentrations of ionic strength and polyamines for the purified enzyme activity were determined and seemed to be very similar to those of the enzyme activity purified from an EBV producing lymphoblastoid cell line. Using the purified enzyme as an antigen and anti-IgA as the secondary antibody, 82% (64/78) and 91% (71/78) of sera from patients with nasopharyngeal carcinoma (NPC) were shown to be positive by dot immunobinding assay and ELISA, respectively. The results suggest that purified E. coli expressed EBV DNase may be useful for preparing specific test for large scale screening of patients with NPC.

Antibodies, Viral↗

PubMed1993

Inhibitory effects of tea extracts and (-)-epigallocatechin gallate on DNA synthesis and proliferation of hepatoma and erythroleukemia cells.

Polyphenols extracted from green or black tea with ethyl acetate were strongly inhibitory for DNA synthesis in HTC rat hepatoma cells and DS19 mouse erythroleukemia cells at concentrations of 0.1-0.2 mg/ml. There was less inhibition with a subsequent black tea fraction extracted with butanol and with the residual water-soluble fraction. Although cell proliferation was inhibited by (-)-epigallocatechin gallate and the tea extracts, there were only marginal effects on differentiation of DS19 cells as judged by hemoglobin synthesis.

Animals↗

PubMed1993

Structure-activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice.

Many arylalkyl isothiocyanates are potent inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in rats and mice. In the mouse, 4-phenylbutyl isothiocyanate (PBITC) and 6-phenylhexyl isothiocyanate (PHITC) exhibited greater inhibition than benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). The present study was conducted to investigate the structure-activity relationships of these four arylalkyl isothiocyanates for their inhibition of NNK oxidation and effects on xenobiotic-metabolizing enzymes in rats and mice. A single dose (0.25 or 1.00 mmol/kg) of each isothiocyanate was given to F344 rats 6 or 24 h before death. The rates of NNK oxidation were decreased in microsomes from the liver, lung and nasal mucosa of rats. Generally, PEITC was more potent than BITC but less potent than PBITC and PHITC. The rates in rat liver microsomes were decreased at 6 h but recovered or increased at 24 h; the rates in rat lung microsomes were markedly decreased at both 6 and 24 h; and the rates in rat nasal mucosa microsomes were also significantly decreased. The same treatment decreased the rat liver N-nitrosodimethylamine demethylase activity dramatically and ethoxyresorufin O-dealkylase and erythromycin N-demethylase activities moderately. However, the rat liver microsomal pentoxy-resorufin O-dealkylase activity was decreased at 6 h but increased at 24 h, with PEITC showing the most marked induction. The rat liver NAD(P)H:quinone oxidoreductase activity was increased 1.4- to 3.3-fold, with PEITC being most effective; and the glutathione S-transferase activity was increased slightly. Similarly, at a single dose of 0.25 mmol/kg (5 mumol/mouse) 24 h before death, PEITC, PBITC, PHITC but not BITC, decreased NNK oxidation in mouse lung microsomes by 40-85%, with PBITC and PHITC showing greater inhibition. Furthermore, all four isothiocyanates extensively inhibited NNK oxidation in rat lung and nasal mucosa microsomes as well as mouse lung microsomes in vitro, with PEITC (IC50 of 120-300 nM) being more potent than BITC (IC50 of 500-1400 nM) but less potent than PBITC and PHITC (IC50 of 15-180 nM). PHITC was a very potent competitive inhibitor of NNK oxidation in mouse lung microsomes with apparent K(i) values of 11-16 nM. These results indicate that PBITC and PHITC are more potent inhibitors of NNK bioactivation in rats and mice than PEITC. In addition, these arylalkyl isothiocyanates could be effective in protecting against the actions of a broad spectrum of carcinogenic or toxic compounds.

Animals↗

PubMed1993

Characterization of a human cell line expressing high levels of cDNA-derived CYP2D6.

We have developed a human B-lymphoblastoid cell, designated h2D6v2, which expresses high levels of CYP2D6 cDNA. Microsomal P450 contents of 160 pmol mg-1 protein were observed. NADPH-fortified microsomes exhibited a substantial capacity to hydroxylate the prototype CYP2D6 substrates bufuralol and debrisoquine. Kinetic parameters, apparent Km, turnover number, Ki for quinidine inhibition and stereospecificity of bufuralol hydroxylation, observed with the human lymphoblast expressed enzyme were similar to those observed in human liver microsomes or purified liver CYP2D6 proteins. Therefore, the human lymphoblast expressed material appears to faithfully reflect the authentic protein. Relative to control cells, h2D6v2 cells were more sensitive to the cytotoxicity and mutagenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), supporting our previous observation with a cell line expressing lower levels of CYP2D6. h2D6v2 microsomes were capable of metabolizing NNK and NNK metabolism and mutagenicity were markedly inhibited by the addition of quinidine, a CYP2D6 inhibitor. h2D6v2 cells coupled with control cells, represent a useful in vitro system for studying xenobiotic metabolism by the clinically important, polymorphic CYP2D6. The human lymphoblast system offers the desirable ability to couple metabolic transformation studies with toxicological endpoints such as cytotoxicity and mutagenicity.

B-Lymphocytes↗

PubMed1993

Inhibition of glucosyltransferase activities of Streptococcus mutans by a monoclonal antibody to a subsequence peptide.

Preliminary analysis indicated that a 19-amino-acid peptide sequence (435 to 453 of GtfC) within a highly conserved region of the glucosyltransferases of the cariogenic streptococci might be functionally important (J.-S. Chia, S.-W. Lin, T.-Y. Hsu, J.-Y. Chen, H.-W. Kwan, and C.-S. Yang, Infect. Immun. 61:1563-1566, 1993). To obtain antipeptide monoclonal antibodies (MAbs), the 19-amino-acid peptide was conjugated to bovine serum albumin and used as an antigen in BALB/c mice. Six immunoglobulin G-secreting hybridoma clones, CJSm18-S1 to -S6, specifically reacted with this peptide and with purified GtfC and GtfD but not with bovine serum albumin in an enzyme-linked immunosorbent assay. The concentrated hybridoma supernatant of all six MAbs inhibited GtfC enzymatic activity but failed to inhibit GtfD, although GtfD contains the same peptide sequence. Further analysis of a purified immunoglobulin G2b MAb from one of the clones, CJSm18-S3, confirmed that this MAb specifically inhibited GtfC enzymatic activity for insoluble-glucan synthesis in a dose-dependent manner. CJSm18-S3, even at high concentrations, had no effect on GtfD, which synthesizes water-soluble glucan exclusively. Furthermore, the in vitro sucrose-dependent adherence of Streptococcus mutans was also inhibited by CJSm18-S3 in a dose-dependent manner. Our results indicate that the peptide containing the N-terminal conserved region of glucosyltransferases is functionally important for both enzymatic activity and bacterial adherence.

Amino Acid Sequence↗

PubMed1993

Analysis of a DNA polymorphic region in the gtfB and gtfC genes of Streptococcus mutans.

We have previously demonstrated the existence of DNA polymorphisms at the 5' coding regions of the gtfB and gtfC genes specifying the streptococcal glucosyltransferases (J.S. Chia, T.Y. Hsu, L.J. Teng, J.Y. Chen, L.J. Hahn, and C.S. Yang, Infect. Immun. 59:1656-1660, 1991). DNA sequence analysis by polymerase chain reaction and direct sequencing revealed that while several nucleotide changes were identified, accounting for the polymorphisms, the amino acids which they code for remain unchanged. The polymorphic region is located in a highly conserved amino terminus of the glucosyltransferases. A peptide of 19 amino acids from this region reversed the inhibiting activity of an antiserum raised against the proteins coded for by the gtfB and gtfC genes. The results suggest that the polymorphic region, varying in DNA but not in amino acid sequences, might specify some biological function.

Amino Acid Sequence↗

PubMed1993

Molecular epidemiology of a variant of coxsackievirus A24 in Taiwan: two epidemics caused by phylogenetically distinct viruses from 1985 to 1989.

In order to know the phylogenetic relationship and the route of transmission of a variant of coxsackievirus A24 (CA24v), an agent that caused four sequential outbreaks of acute hemorrhagic conjunctivitis from 1985 to 1989 in Taiwan, the nucleotide sequence variations in the virus-encoded proteinase 3C region (549 nucleotides) were studied with 19 isolates. The prototype strain (EH24/70), four isolates from Japan, and two isolates from Hong Kong were used for comparison. The nucleotide sequences of the Taiwan strains from the 1985-1986 and 1988-1989 epidemics were closely related within each epidemic, while they were more distantly related between strains from two epidemics. Phylogenetic analysis by the unweighted pairwise grouping method of the arithmetic average revealed that the 19 Taiwan isolates had diverged into two groups, 1985-1986 and 1988-1989 groups. The time at which these two groups diverged was estimated to be around May 1982, more than 3 years prior to the first appearance of the CA24v epidemic in Taiwan. On each occasion, the viruses caused a 2-year epidemic and then disappeared. The Taiwan isolates from 1985 to 1986 were closely related to the Japan isolates from 1985 to 1986 and the Taiwan isolates from 1988 to 1989 were phylogenetically close to the 1989 Japan isolates, indicating that Taiwan and Japan had two common-source outbreaks. However, none of the 1988 Taiwan isolates were phylogenetically close to the 1988 Japan or Hong Kong isolates. The evidence revealed that Taiwan has had two repeated but discontinuous introductions of CA24v since its first appearance in Taiwan in 1985. None of the other CA24v strains have been detected so far.

Base Sequence↗

PubMed1993

Hepatitis C markers in hemodialysis patients.

The prevalence of hepatitis C virus (HCV) infection among the patients of a hemodialysis unit in Taiwan was determined by an immunoblot and reverse transcriptase-polymerase chain reaction algorithm to be 58.8% (67 of 114 patients) after serological surveys with two advanced-generation enzyme-linked immunosorbent assays (ELISAs) for anti-HCV and a C 100-3 single-antigen test. The results of the second-generation ELISAs, the supplementary immunoblot test, and the test for HCV RNA were in good agreement with each other, from 86.0 to 98.2%. The first-generation C 100-3 test lacked the sensitivity of the four other systems. The two advanced-generation screening ELISAs for anti-HCV, a multiple-recombinant-antigen test, the Abbott second-generation ELISA, and a synthetic peptide multiple-antigen test, the UBI HCV EIA, provided reliable and virtually equivalent detection of potentially infected blood. Antibodies to capsid 1 and capsid 2 determinants of the Liatek immunoblot system were the most frequently detected reactivities to HCV in the HCV-infected hemodialysis patients. The percentage of HCV-infected patients with abnormal liver function (alanine aminotransferase level, greater than 100 IU/liter) was higher than that of the uninfected patients. The prevalence of HCV infection was correlated to the duration of hemodialysis treatment and the amount of blood transfused, and the most common transmission mode was thought to be patient-to-patient transmission through the dialysis equipment. Several means of reducing the frequency of transmission between hemodialysis patients are suggested.

Adult↗

PubMed1993

Increased immunogenicity and protective efficacy in outbred and inbred mice by strategic carboxyl-terminal truncation of Japanese encephalitis virus envelope glycoprotein.

We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a strategically truncated E glycoprotein, approximately 80% of the N-terminal sequence, and compared their antigenic structure and protective immunity in mice. The truncation site in the JEV E glycoprotein sequence corresponds to the position that had been shown to increase the immunogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis of the JEV E glycoprotein in recombinant virus-infected cells showed that C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycoprotein was detected predominantly intracellularly, while a small fraction (< 2%) was present on the cell surface. On the other hand, the truncated 80% E glycoprotein exhibited an alteration in the intracellular transport pathway resulting in increased accumulation (10-25%) on the cell surface and secretion (6-10%) into the medium. The C-terminally truncated E glycoprotein induced a greater antibody response and a higher level of protective immunity than did the full-length E glycoprotein in outbred CD-1 mice as well as in two strains of inbred mice that differ in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/Bl mice, which possess a dominant autosomal genetic locus that controls resistance to a high dose of ip infection of JEV or the capacity to acquire resistance to intracerebral JEV infection, truncated E glycoprotein induced a higher titer of JEV neutralizing antibodies.

Amino Acid Sequence↗

PubMed1993

Analysis of Epstein-Barr virus BamHI F DNA fragment in nude mouse-passaged nasopharyngeal carcinoma tissues.

Two nude mouse-passaged nasopharyngeal carcinoma (NPC) tissues, NPC-295 and NPC-306, were different in ability to transform cord blood lymphocytes and contained Epstein-Barr virus (EBV) genomes with difference in BamHI F DNA fragment. Four clones containing DNA sequences of the BamHI F fragment (54,853-62,249) were obtained from genomic libraries of NPC-295 and NPC-306 and their partial restriction enzyme maps and sequences were determined. The restriction enzyme maps of EBV DNA at the BamHI F fragment in NPC-295 and NPC-306 appeared to be similar to that of EBV B95-8 strain. However, 8 nucleotide differences were revealed between NPC-295 and the B95-8 strain when 566 nucleotides (55,405-55,970) were compared, and 15 out of 677 nucleotides analyzed (55,410-56,086) were different between NPC-306 and B95-8.

Animals↗

PubMed1993

Age- and gender-related variations in the activities of drug-metabolizing and antioxidant enzymes in the white-footed mouse (Peromyscus leucopus).

The effects of aging on the activities of drug-metabolizing enzymes and antioxidant enzymes were studied in male and female White-Footed mice (Peromyscus leucopus) at ages of 6, 8, 12, 18, 24, 30, 36, and 48 months. Male mice had significantly higher liver microsomal cytochrome P450 (P450) content and NADPH:cytochrome P450 oxidoreductase (P450 reductase) activities than females at all age groups. Many of the P450-dependent enzyme activities were also generally higher in males. Female mice showed age-dependent decreases in P450 content and the activities of P450 reductase, pentoxyresorufin O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMAd) in the liver from 6 to 24 months; while, the males showed an age-dependent decrease only for the liver PROD activity from 6 to 24 months. The old males (30-month old) appeared to have significantly higher activities for 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone and androstenedione formation than the middle-aged (6- to 18-month old) and very old (48-month old) males. Females showed age-dependent decreases for the formation of 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone in liver microsomes from 6 to 24 months. Lung microsomes from 6- and 8-month old males had much higher activities of ethoxyresorufin O-deethylase (EROD) and PROD than older males. The total NNK alpha-hydroxylation activities changed in the same pattern as lung microsomal EROD and PROD activities in both male and female mice. The activities of several phase II drug-metabolizing enzymes: glutathione S-transferase (GST), DT-diaphorase, sulfotransferase and UDP-glucuronosyl-transferase (UDPGT) did not show any significant age-dependent changes, with the possible exception that the GST activity in males decreased from 18 to 36 months. Males had about 3-fold higher UDPGT activities than females among all age groups. Glutathione peroxidase activities were drastically lower in old and very old males, and 6 to 24 months old males had significantly higher activities than the corresponding females. In females, superoxide dismutase activities decreased linearly to extremely low levels as mice aged. Catalase activities showed a tendency for increase with age in males. In conclusion, some P450-dependent activities and antioxidant enzymes, but not phase II drug-metabolizing enzymes, showed age-dependent changes; and most of these changes occur from 6 to 24 months. The demographic attributes of the White-Footed mouse are well-suited for physiological and biochemical studies of aging and can complement the more standard laboratory mouse model with its typical two year life span.

Age Factors↗

PubMed1992

Inhibitory effect of green tea on the growth of established skin papillomas in mice.

In 10 separate experiments, mice with established chemically induced or UV light-induced skin papillomas were treated continuously with green tea in the drinking water or with i.p. injections of a green tea polyphenol fraction or (-)-epigallocatechin gallate three times a week for 4-10 weeks. Partial tumor regression or > 90% inhibition of tumor growth, as measured by changes in tumor volume per mouse, was observed in 5 experiments, and marked inhibition of tumor growth (46-89%) was observed in 5 additional experiments. Treatment of the mice with green tea or green tea constituents had an inhibitory effect on body weight increases in several but not all of the studies. Examination of the data from all ten experiments revealed that complete tumor regression occurred in 14 of 346 papilloma-bearing mice (4%) that were treated with green tea in the drinking water or with i.p. injections of green tea constituents, whereas none of the 220 papilloma-bearing control mice treated with only vehicle exhibited complete tumor regression. These observations indicate that oral administration of green tea, i.p. administration of a green tea polyphenol fraction, or i.p. administration of (-)-epigallocatechin gallate inhibited the growth and/or caused the regression of established experimentally induced skin papillomas.

9,10-Dimethyl-1,2-benzanthracene↗