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Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 109 records · Page 6Linked to original sources
PubMed1999

Solar retinopathy: a case report.

Sun-gazing is the main cause of solar retinopathy. A 20-year-old inebriated man lying in a park gazed at the sun for approximately three hours at noon. Forty-eight hours after sun-gazing, the patient experienced the symptoms of blurred vision, erythropsia, and central scotoma in the left eye. Visual acuity decreased from 6/6 to 6/60 in the left eye and fundi examinations showed a round, yellowish-white discoid lesion on the left fovea and a smaller one on the right fovea. Fluorescein angiography showed early dye leakage in the fovea of the left eye, that increased gradually in size and became fuzzy at the foveal border in the late phase. A small, central scotoma of the left eye was also found in the visual field test. One month later, the lesion in the fovea of the left eye became smaller and was surrounded by a coarse pigmented halo. Fluorescein angiography showed a window defect in the retinal pigment epithelium. Visual field testing disclosed that the central scotoma persisted, but became smaller. Six months after sun-gazing, a lamellar hole in the fovea of the left eye was detected by optical coherence tomography. The visual acuity was 6/6 in the right eye and 6/60 in the left eye, and was unchanged at the end of the six-month follow-up period.

Adult↗
PubMed1999

Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans.

The objective of this Phase I/II study was to assess the potential for green tea to be used as a colorectal cancer chemopreventive agent. This study measured the dose-related biological effects of administration of a single dose of green tea on the rectal mucosa of normal volunteers. Volunteers were admitted to the Robert Wood Johnson Medical School Clinical Research Center for 24 h. Baseline blood and rectal biopsy samples were obtained before the volunteers drank 0.6, 1.2, or 1.8 g of green tea solids dissolved in warm water. Blood samples were taken 2, 4, 8, and 24 h after the tea administration. Rectal biopsies were obtained at 4, 8, and 24 h. Prostaglandin E2 (PGE2) levels were analyzed by ELISA. Tea polyphenol levels in the blood, urine, and rectal tissue were measured by high-performance liquid chromatography using a Coulochem electrode array detection system. Statistical comparisons were made using ANOVA. Decreased levels of PGE2 in rectal mucosa were observed at 4 and 8 h after consumption of green tea. There was no correlation between inhibition of PGE2 and tissue or plasma levels of tea polyphenols. Ten of 14 subjects demonstrated a response to green tea, as evidenced by at least a 50% inhibition of PGE2 levels at 4 h. We conclude that green tea constituents have biological activity in inhibiting PGE2 synthesis. Given the 71% "response rate," we believe these data support the study of green tea as a colorectal chemopreventive agent in more long-term Phase II trials.

Administration, Oral↗
PubMed1999

Seroepidemiology of human parvovirus B19 in Taiwan.

In order to determine the prevalence and risk factors of human parvovirus B19 (B19) infection in Taiwan, a seroepidemiological study was carried out in 19 townships. Serum samples were collected from 862 healthy residents, who were selected by stratified random sampling from various study areas. They were chosen from four different ethnic groups including aborigines, Fukien Taiwanese, Hakka Taiwanese, and mainland Chinese. Serum samples were screened for B19 IgG antibody by indirect antibody capture enzyme-linked immunosorbent assay (ELISA) and B19 IgM by IgM antibody capture (MAC)-ELISA, respectively. The overall prevalence of anti-B19 IgG and anti-B19 IgM was 32.8% and 0.35%, respectively. The anti-B19 seropositive rate in females was significantly higher than that of males (36.4% vs. 29.4%, P < .001). The age-sex-adjusted seropositive rate in urban townships (39.9%) was higher than that in aboriginal townships (30.5%, P < .001). The seropositive rate increased significantly with age showing a dose-response relationship (P=0.0001 based on a trend test). Blood transfusion was found to be associated with an increased seropositive rate showing a multivariate-adjusted odds ratios of 1.6.

Adolescent↗
PubMed1999

Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies.

Because of the possible application of tea in the prevention of oral and esophageal cancers, the salivary levels of tea catechins were determined in six human volunteers after drinking tea. Saliva samples were collected after thoroughly rinsing the mouth with water. After drinking green tea preparations equivalent to two to three cups of tea, peak saliva levels of (-)-epigallocatechin (EGC; 11.7-43.9 microg/ml), EGC-3-gallate (EGCG; 4.8-22 microg/ml), and (-)-epicatechin (EC; 1.8-7.5 microg/ml) were observed after a few minutes. These levels were 2 orders of magnitude higher than those in the plasma. The elimination half-life (t(1/2)) of the salivary catechins was 10-20 min, much shorter than that of the plasma. Holding a tea solution in the mouth for a few minutes without swallowing produced even higher salivary catechin levels, but taking tea solids in capsules resulted in no detectable salivary catechin level. Holding an EGCG solution in the mouth resulted in EGCG and EGC in the saliva and, subsequently, EGC in the urine. The results suggest that EGCG was converted to EGC in the oral cavity, and both catechins were absorbed through the oral mucosa. A catechin esterase activity that converts EGCG to EGC was found in the saliva. The enzyme was likely of human origin, but the activity was not inhibited by common human esterase inhibitor. The present results suggest that slowly drinking tea is a very effective way of delivering rather high concentrations of catechins to the oral cavity and then the esophagus.

Absorption↗
PubMed1998

Epstein-Barr virus DNase contains two nuclear localization signals, which are different in sensitivity to the hydrophobic regions.

The DNase of Epstein-Barr virus (EBV) is a 470-amino-acid protein which possesses both endonuclease and exonuclease activities and accepts both double-stranded DNA and single-stranded DNA as substrates. It has been reported that this protein may be found in the nucleus and/or cytoplasm of infected cells. In this study, using cell fractionation and immunoblotting to determine the distribution of EBV DNase in Akata cells stimulated with anti-human immunoglobulin G antibody (anti-IgG), the DNase was found to be located predominantly in the nucleus. To map the signals in DNase which mediate its nuclear localization, we monitored the nuclear transport of fusion proteins consisting of various fragments of EBV DNase linked to a cytoplasmic protein, beta-galactosidase (beta-Gal). The results demonstrated that two regions of the DNase with nuclear localization signal (NLS) activity, designated NLS-A (amino acids 239-266) and NLS-B (amino acids 291-306), were able independently to localize the beta-Gal to the nuclei of HEp-2 and HeLa cells. Five basic residues (R or K) were found in each NLS and distributed differently in primary structure. The basic domains and flanking residues of NLS-A and NLS-B are 250YKRPCKRSFIRFI262 and 294LKDVRKRKLGPGH306, respectively. Further examination of these sequences revealed that NLS-A contains bulky aromatic amino acids (Y and F) which may diminish its capacity to act as a strong NLS and lacks the typical proline and glycine helix-breakers. However, NLS-B contains typical proline and glycine helix-breakers and the histidine residue at amino acid 306 is required for NLS activity. In addition, two hydrophobic regions within the DNase were found to inhibit the function of NLS-A but not NLS-B, suggesting that these two domains are different types of NLSs and differ in their sensitivity to hydrophobic regions in the context of protein structure.

Base Sequence↗
PubMed1998

Molecular basis for interactions of G protein betagamma subunits with effectors.

Both the alpha and betagamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) communicate signals from receptors to effectors. Gbetagamma subunits can regulate a diverse array of effectors, including ion channels and enzymes. Galpha subunits bound to guanine diphosphate (Galpha-GDP) inhibit signal transduction through Gbetagamma subunits, suggesting a common interface on Gbetagamma subunits for Galpha binding and effector interaction. The molecular basis for interaction of Gbetagamma with effectors was characterized by mutational analysis of Gbeta residues that make contact with Galpha-GDP. Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-beta2, and beta-adrenergic receptor kinase revealed the Gbeta residues required for activation of each effector and provides evidence for partially overlapping domains on Gbeta for regulation of these effectors. This organization of interaction regions on Gbeta for different effectors and Galpha explains why subunit dissociation is crucial for signal transmission through Gbetagamma subunits.

Adenosine Diphosphate Ribose↗
PubMed1998

Distinct regions of EBV DNase are required for nuclease and DNA binding activities.

Epstein-Barr virus (EBV) DNase possesses both endonuclease and exonuclease activities and accepts both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) as substrates. To map regions of EBV DNase responsible for nuclease and DNA binding activities, a series of mutant DNase polypeptides was expressed using a bacterial system for the nuclease assay and in an in vitro transcription/translation system to assay binding activity to dsDNA or ssDNA cellulose. The results indicated that the C-terminus of EBV DNase, residues 450-460, is essential for nuclease activity but dispensable for DNA binding. However, deletion of residues 441-470 resulted in the loss of both nuclease and DNA binding activities. Substitution of Phe452 and Val458 led to inactive enzymes. In the N-terminus, deletion of residues 23-28 and residues 7-61 resulted in the loss of nuclease activity but the DNA binding activities of the deleted enzymes were intermediate and low, respectively. Mutation of Leu23 to Gly showed drastically reduced nuclease activity but its DNA binding ability was not affected. Based on the amino acid sequence alignment of various herpesvirus DNases, we chose four highly conserved and two less well conserved regions as controls for mutagenesis studies. These six internal deletion (ID) mutants were prepared using a recombinant PCR method. Each of the polypeptides was expressed in a bacterial system for the nuclease assay and using an in vitro transcription/translation system for the DNA binding assay. DNA binding and nuclease activities of all six internal deletion mutants were abolished, except that mutant ID2, with deletion of residues 138-152, retained an intermediate ability to bind DNA. These data indicate that since mutations at distinct regions within EBV DNase resulted in the loss of nuclease and/or DNA binding activities, it is suggested that these distinct regions are required for maintenance of an intact and highly ordered structure(s) for both activities.

Amino Acid Sequence↗
PubMed1998

Elevated extracellular glutamate concentrations increased malondialdehyde production in anesthetized rat brain cortex.

Oxidative stress is believed to be involved in the damaging mechanism of excitotoxic insult. Thus, we investigated the effect of elevated extracellular glutamate levels on malondialdehyde production, a common index of lipid peroxidation, in anesthetized rat brain cortex. Elevation of extracellular glutamate levels was achieved either by exogenously perfusing glutamate solutions, or by perfusing L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of glutamate uptake transporter, through an implanted microdialysis probe. Malondialdehyde levels in the microdialysates, which were reacted with thiobarbituric acid, were analyzed by a high performance liquid chromatography system equipped with a fluorescence detector. Perfusion of glutamate (1.5 and 15 mM) resulted in dose-dependent increases in extracellular malondialdehyde production (as high as a 6-fold increase in malondialdehyde production following perfusion of 15 mM glutamate solution). PDC (3.14 and 31.4 mM), not only significantly increased the extracellular glutamate levels in a dose-dependent manner, but also dramatically increased malondialdehyde production (as high as 20-fold increase). These results suggest that excitotoxicity induces oxidative stress in anesthetized rat brain cortex, as evidenced by the glutamate-induced increase in malondialdehyde production.

ATP-Binding Cassette Transporters↗
PubMed1998

An intravitreal sustained-release triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy.

OBJECTIVE: To determine the efficacy and pharmacokinetics of an intravitreal sustained-release triamcinolone acetonide and 5-fluorouracil (TA/5-FU) codrug in the treatment of experimental proliferative vitreoretinopathy (PVR). METHODS: The therapeutic efficacy of the TA/5-FU codrug was determined in a rabbit model that simulates human PVR. Intravitreal levels of triamcinolone and 5-fluorouracil were measured at different time points and drug release in vitro was tested. Toxic effects were evaluatedby electroretinograpy, clinical examination, and light microscopy. RESULTS: Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug-related toxic effects evident on clinical or histopathologic examination of eyes containing the TA/5-FU codrug. CONCLUSIONS: The intravitreal sustained-release TA/5-FU codrug effectively inhibits the progression of PVR in a rabbit model that closely resembles PVR in humans. The TA/5-FU codrug may simultaneously target different components of the wound-healing response.

Animals↗
PubMed1998

Content of reduced glutathione and consequences in recipients of glucose-6-phosphate dehydrogenase deficient red blood cells.

The red blood cell glucose-6-phosphate dehydrogenase (G6PD) activity of every donor was examined with automatic enzyme-coupled method. The technique of molecular biology was applied to determine the DNA mutations for the 97 donors with undetectable G6PD activity. The concentration of reduced glutathione (GSH) in the stored RBC of the 97 G6PD-deficient donors and 124 normal donors was determined with the technique of high performance liquid chromatography. Routine blood counts, bilirubin and haptoglobin levels were used to evaluate posttransfusional hemolysis for the 48 adult patients transfused with 1 U G6PD deficient and 1 U normal RBC. Most (88, 90.7%) of the 97 donors were confirmed to be G6PD deficient at the DNA level. At each age interval of storage, the GSH concentration of G6PD-deficient RBC was significantly different from that of normal RBC. The total average value of GSH (pmol/gHb) was 2.52 +/- 0.95 (mean +/- 1 standard deviation) vs. 3.74 +/- 1.43 (P < 0.001). Hemoglobin, hematocrit, bilirubin, and haptoglobin levels in the patients receiving G6PD-deficient RBC were not statistically different from those in the recipients of normal RBC; even though the age of stored blood was 26-35 days. Within the same group of patients, the results of bilirubin and haptoglobin were not significantly changed before and after transfusion. The results of this study show that the GSH concentration in the stored blood of G6PD deficient donors was 67% of that in the normal donors. However, hemolysis does not occur in adult patients transfused with 1 U G6PD-deficient RBC. It seems unnecessary to screen G6PD activity for donors of adult recipients in Taiwan.

Adult↗
PubMed1998

Antibody against the Epstein-Barr virus BHRF1 protein, a homologue of Bcl-2, in patients with nasopharyngeal carcinoma.

The Epstein-Barr virus (EBV) open reading frame BHRF1, a homologue of the oncogene bcl-2, was cloned from a patient with nasopharyngeal carcinoma (NPC) and overexpressed in Escherichia coli. The resulting recombinant BHRF1 fusion protein, with an apparent molecular weight of 35 KD, was used as antigen in an immunoblotting assay for IgG antibody in human sera. Anti-BHRF1 antibody was detected in 57 (61.3%) of 93 patients with NPC, 5 (5.7%) of 87 patients with nonmalignant diseases of the nasopharynx, and in 1 (1.3%) of 78 healthy blood donors. The positivity rate in these nonmalignant patients was 4.4 times that of the normal controls. Negative results were observed in four patients with infectious mononucleosis and patients with other cancers, including 4 with esophageal cancer, 11 with lung cancer, 10 with lymphoma, 13 with gastric carcinoma, 10 with cervical carcinoma, and 10 with other head and neck cancers. Antibody neutralizing EBV DNase and IgA antibody to viral capsid antigen (VCA) were assayed in parallel. The results showed that 7.5% of the NPC patients were negative for anti-DNase and anti-VCA antibodies and EBV infection could be detected by the anti-BHRF1 antibody alone. The demonstration of anti-BHRF1 antibody in most NPC sera strongly supports the hypothesis that the EBV BHRF1 protein is expressed in most NPC patients and its specific antibody can be a useful marker for the diagnosis of NPC.

Antibodies, Viral↗
PubMed1998

Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat.

Acetaminophen is a mild analgesic and antipyretic agent known to cause centrilobular hepatic necrosis at toxic doses. Although this may be due to a direct interaction of reactive acetaminophen metabolites with hepatocyte proteins, recent studies have suggested that cytotoxic mediators produced by parenchymal and nonparenchymal cells also contribute to the pathophysiological process. Nitric oxide is a highly reactive oxidant produced in the liver in response to inflammatory mediators. In the present studies we evaluated the role of nitric oxide in the pathophysiology of acetaminophen-induced liver injury. Treatment of male Long Evans Hooded rats with acetaminophen (1 g/kg) resulted in damage to centrilobular regions of the liver and increases in serum transaminase levels, which were evident within 6 hours of treatment of the animals and reached a maximum at 24 hours. This was correlated with expression of inducible nitric oxide synthase (iNOS) protein in these regions. Hepatocytes isolated from both control and acetaminophen-treated rats were found to readily synthesize nitric oxide in response to inflammatory stimuli. Cells isolated from acetaminophen-treated rats produced more nitric oxide than cells from control animals. Production of nitric oxide by cells from both control and acetaminophen-treated rats was blocked by aminoguanidine, a relatively specific inhibitor of iNOS. Arginine uptake and metabolism studies revealed that the inhibitory effects of aminoguanidine were due predominantly to inhibition of iNOS enzyme activity. Pretreatment of rats with aminoguanidine was found to prevent acetaminophen-induced hepatic necrosis and increases in serum transaminase levels. This was associated with reduced nitric oxide production by hepatocytes. Inhibition of toxicity was not due to alterations in acetaminophen metabolism since aminoguanidine had no effect on hepatocyte cytochrome P4502E1 protein expression or N-acetyl-p-benzoquinone-imine formation. Taken together, these data demonstrate that nitric oxide is an important mediator of acetaminophen-induced hepatotoxicity.

Acetaminophen↗
PubMed1998

Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis.

OBJECTIVE: Uveitis often is a chronic disease requiring long-term medical therapy. Despite treatment, the disease may be difficult to control and may produce serious, vision-threatening ocular complications. In this study, the authors determined whether an intravitreal cyclosporine-sustained delivery device was effective in the treatment of ocular inflammation in a rabbit model of uveitis. METHODS: New Zealand White rabbits were immunized subcutaneously with Mycobacterium tuberculosis H37Ra antigen. Fourteen days later, sustained-release cyclosporine devices were implanted into the vitreous cavity of the right eye of experimental rabbits. Control animals received sham devices. Seven days after device implantation, rabbits were challenged with an intravitreal injection of tuberculin antigen. To simulate chronic inflammation with exacerbations, some animals were rechallenged with intravitreal antigen on day 21 after device implantation. Inflammation was assessed clinically by a masked observer who graded anterior chamber cells, flare, corneal neovascularization, iris congestion, and vitreous opacity daily until day 7 and on day 13 after the initial intravitreous challenge, and on days 1 and 2 after the rechallenge. Retinal function was evaluated by electroretinography. Animals were killed 3, 6, 8, and 14 days after the initial intravitreal challenge and on the second day after rechallenge for aqueous leukocyte count, protein measurement, and histologic examination. The number of aqueous and peripheral blood proliferating lymphocytes and the subset of CD4+ T cells were determined by flow cytometry. High-performance liquid chromatography was used to measure cyclosporine A levels in vitreous and peripheral blood. Light microscopy was used to evaluate the eyes histopathologically. RESULTS: By clinical criteria, treated eyes had significantly less inflammation than untreated eyes. The number of aqueous cells and protein concentration determined quantitatively paralleled the clinical assessment of anterior chamber cells and flare. The electroretinography B-wave was depressed significantly in untreated eyes compared with that of treated eyes (P < 0.02). Histopathologic examination results showed marked inflammation and tissue disorganization in untreated eyes, whereas cyclosporine-treated eyes had preserved architecture and greatly reduced inflammatory cells. Intravitreal cyclosporine remained at therapeutic levels for at least 6 months after intravitreal device implantation, whereas blood levels were low to nondetectable. CONCLUSIONS: The intravitreal cyclosporine A device effectively suppresses ocular inflammation in a rabbit model of uveitis. This device may be useful in the treatment of patients with severe chronic uveitis who are intolerant to currently available therapies.

Animals↗
PubMed1998

Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea.

We investigated the effects of black tea (BT) and green tea (GT) infusion on the spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice. Female A/J mice, 6 weeks of age, were allocated into five groups (50 per group) and were given the following as the sole source of drinking fluid: (i) deionized water (control group), (ii) 0.5% BT, (iii) 1% BT, (iv) 2% BT and (v) 1% GT. After 60 weeks, the mice were killed by decapitation. Lung tumor incidence, multiplicity and volume were significantly lower in the 2% BT group as compared with the controls (27 versus 52%, 0.33 versus 0.72 tumors/mouse and 4.27 versus 38.3 mm3, respectively). The 1% GT group had significantly lower lung tumor multiplicity (0.41/mouse), while the 1% BT group had significantly decreased tumor volume (7.17 mm3). Rhabdomyosarcomas were found in 34% of the mice in the control group, and both the 1 and 2% BT groups had significantly lower incidences at 13 and 14%, respectively. The mice in the 2% BT group weighed 16% less than those in the control group, although they consumed more food than the control group. The other tea-consuming groups also weighed less than the control group (7.8-11%) while consuming more food and fluid. In a separate experiment, similar carcinogenesis inhibition was also observed in female A/J mice that were given 0.6% and then 0.3% instant black tea for 52 weeks. These results demonstrate the inhibitory activity of BT against the spontaneous formation of lung tumors and rhabdomyosarcomas in mice.

Animals↗
PubMed1998

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols.

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.

Adenocarcinoma↗
PubMed1998

Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in the human esophagus.

Esophageal cancer has been associated with tobacco smoking, and nitrosamines are possible causative agents for this cancer. The present study investigated the metabolism of the tobacco carcinogens N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosodimethylamine (NDMA), as well as the presence of xenobiotic-metabolizing enzymes in human esophageal tissues from individuals in the United States and Huixian, Henan Province, China (a high-risk area for esophageal cancer). All esophageal microsomal samples activated NNN and the metabolic rate was 2-fold higher in the esophageal samples from China than the USA. All microsomal samples activated NDMA. However, most of the microsomal samples did not activate NNK. Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation of NNN-derived keto acid by 20-26% in the esophageal microsomes. The activities for NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase, NAD(P)H: quinone oxidoreductase and glutathione S-transferase were present in the esophageal samples. Coumarin 7-hydroxylase (a representative activity for P450 2A6) activity was not detected in the esophageal microsomal samples. The activities for nitrosamine metabolism and xenobiotic-metabolizing enzymes were decreased (by 30-50%) in the squamous cell carcinomas compared with their corresponding non-cancerous mucosa. The presence of activation and detoxification enzymes in the esophagus may play an important role in determining the susceptibility of the esophagus to the carcinogenic effect of nitrosamines. Our results suggest that P450s 3A4 and 2E1 are involved in the activation of NNN and NDMA, respectively, in the human esophagus.

Adult↗
PubMed1998

Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma.

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.

Adenocarcinoma↗