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Biomedical subjects

S L Wang

Publications and source records attributed to S L Wang.

At least 73 records · Page 4Linked to original sources

Investigation of the clinical value of total saliva flow rates.

The symptom of dry mouth was correlated with unstimulated (UWSFR) and stimulated (SWSFR) whole-saliva flow rate on chewing medical paraffin in 62 patients with dry-mouth complaints (30 with Sjögren's syndrome, 32 with sialosis) and 23 controls. The symptom of dry mouth was classified into grades 0,1,2,3,4 according to a Treatment Emergent Symptom Scale (TESS). UWSFR and SWSFR were determined after fasting in the morning. UWSFR was 0.070 +/- 0.089 ml/min in Sjögren's syndrome, 0.175 +/- 0.115 ml/min in sialosis, 0.330 +/- 0.188 ml/min in controls. SWSFR was 0.709 +/- 0.720 ml/min in Sjögren's syndrome, 1.561 +/- 0.867 ml/min in sialosis, 1.894 +/- 0.661 ml/min in controls. A highly significant correlation was found between TESS score and UWSFR and between TESS score and SWSFR. Only UWSFR was decreased in the patients with a TESS score of 1 or 2, while both UWSFR and SWSFR were significantly decreased in the patients with TESS scores of 3, 4. It is concluded that UWSFR is more sensitive in relation to dry-mouth complaints than SWSFR, and that a mild dry mouth is mainly related to decreased UWSFR.

Adult↗

Oncogenic ras induces gastrin gene expression in colon cancer.

BACKGROUND & AIMS: The expression of gastrin, as a tumor growth factor, is significantly increased in some colon cancers compared with the low levels found in normal mucosa. The aim of this study was to elucidate the transcriptional mechanisms of gastrin induction in colon cancer. METHODS: Gastrin messenger (mRNA) levels and K-ras genotype were determined in colon cancer cell lines and surgical specimens. Colon cancer cells were transfected with oncogenic ras expression vectors, and transcriptional activity was assayed with gastrin-luciferase reporter genes. RESULTS: Colon cancer cell lines and tissues with K-ras mutations all had significantly higher gastrin mRNA levels than those that were ras wild type. Treatment of several ras mutant cell lines with PD98059, an inhibitor of mitogen-activated protein kinase kinase, resulted in a decrease in endogenous gastrin mRNA levels. The effects of ras on gastrin expression appeared to be mediated through the gastrin promoter because transfection of oncogenic ras and activated raf expression vectors both induced gastrin-promoter, luciferase-reporter genes. The inductive effects of oncogenic ras could be blocked by the coexpression of dominant negative forms of raf and extracellular regulated kinase. CONCLUSIONS: Oncogenic ras induces gastrin gene expression through activation of the Raf-MEK-ERK signal transduction pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗

Sialographic characterization of the normal parotid gland of the miniature pig.

OBJECTIVE: To characterize the structure of the parotid gland of the miniature pigs (minipig). METHODS: Sialographic, anatomical, histological and ultrastructural studies of the parotid gland were performed on 11 minipigs. RESULTS: Sialograms showed a long main duct and a triangular shaped gland. All branching ducts extended from the inferior-posterior margin of the main duct. No accessory glands were found. Typical serous acini were found microscopically and histochemically. CONCLUSION: This study provides basic structural information on the parotid gland of the minipig.

Animals↗

Changes in populations of Listeria monocytogenes inoculated on packaged fresh-cut vegetables.

A variety of wholesale and retail packaged vegetables and salads were inoculated with a mixture of strains of Listeria monocytogenes and incubated at 4 and 10 degrees C. Whole rutabagas, butternut squash, and onions, as well as packaged Caesar salad, carrots, coleslaw mix, and stir-fry vegetables were purchased from local supermarkets in the Ottawa area. L. monocytogenes population levels remained constant on all fresh-cut vegetables stored at 4 degrees C for 9 days, except for carrots and butternut squash: counts of cell numbers declined on carrots and increased on the butternut squash. Fresh-cut vegetables stored at 10 degrees C, however, supported good growth of L. monocytogenes on all vegetables tested, except for chopped carrots, where the population decreased approximately 2 log units over a 9-day storage period. As in the situation with the produce stored at 4 degrees C, butternut squash supported the highest rate of cell growth. In addition, Caesar salad and coleslaw mix were kept at 25 degrees C for 1 or 2 days before subsequent storage at 4 or 10 degrees C to stimulate extreme temperature-abuse conditions. In Caesar salad stored at 4 degrees C, by day 6 an initial 24- and 48-h temperature abuse at 25 degrees C led to a 1.21- and 2.55-log-unit population increase, respectively, over the control. Similar increases were observed on Caesar salads stored at 10 degrees C. Compared to Caesar salad, coleslaw mix temperature-abused at 25 degrees C and then stored at 4 degrees C supported slightly greater increases in the population of L. monocytogenes, i.e., a 3.22- and 3.83-log-unit increase over the control for the 1- and 2-day abused samples, respectively. Coleslaw mix samples temperature-abused and then stored at 10 degrees, however, only showed log unit increases of 1.75 and 1.94, respectively, compared to the controls. These results point to the importance of strict temperature control to prevent or reduce the growth of L. monocytogenes cells on fresh-cut vegetables.

Colony Count, Microbial↗

Coordinate regulation of lipogenesis, the assembly and secretion of apolipoprotein B-containing lipoproteins by sterol response element binding protein 1.

Stable plasmid-driven expression of the liver-specific gene product cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) was used to alter the cellular content of transcriptionally active sterol response element binding protein 1 (SREBP1). As a result of stable expression of 7alpha-hydroxylase, individual single cell clones expressed varying amounts of mature SREBP1 protein. These single cell clones provided an opportunity to identify SREBP1-regulated genes that may influence the assembly and secretion of apoB-containing lipoproteins. Our results show that in McArdle rat hepatoma cells, which normally do not express 7alpha-hydroxylase, plasmid-driven expression of 7alpha-hydroxylase results in the following: 1) a linear relationship between (i) the cellular content of mature SREBP1 and 7alpha-hydroxylase protein, (ii) the relative expression of 7alpha-hydroxylase mRNA and the mRNA's encoding the enzymes regulating fatty acid, i.e. acetyl-CoA carboxylase and sterol synthesis, i.e. HMG-CoA reductase, (iii) the relative expression of 7alpha-hydroxylase mRNA and microsomal triglyceride transfer protein mRNA, a gene product that is essential for the assembly and secretion of apoB-containing lipoproteins; 2) increased synthesis of all lipoprotein lipids (cholesterol, cholesterol esters, triglycerides, and phospholipids); and 3) increased secretion of apoB100 without any change in apoB mRNA. Cells expressing 7alpha-hydroxylase contained significantly less cholesterol (both free and esterified). The increased cellular content of mature SREBP1 and increased secretion of apoB100 were concomitantly reversed by 25-hydroxycholesterol, suggesting that the content of mature SREBP1, known to be decreased by 25-hydroxycholesterol, mediates the changes in the lipoprotein assembly and secretion pathway that are caused by 7alpha-hydroxylase. These data suggest that several steps in the assembly and secretion of apoB-containing lipoproteins by McArdle hepatoma cells may be coordinately linked through the cellular content of mature SREBP1.

Acetyl-CoA Carboxylase↗

Time-dependent alteration of epidermal growth factor receptor in rat stomach by ethanol feeding.

This study investigated the time-dependent effects of ethanol (EtOH) feeding on epidermal growth factor binding and epidermal growth factor-mediated functions in the stomach. Adult male rats were fed either an isocaloric control or EtOH-containing liquid diet (36% total calories as EtOH) for 2, 4 and 6 weeks. At the end of each feeding period, animals were sacrificed and the stomach was dissected for the sample preparation. EtOH caused a time-dependent alteration (r = 0.89) of the 125I-epidermal growth factor binding to the gastric mucosal membrane (% control: week 2, 114%; week 4, 64%* and week 6, 45%*, n = 5, *P < 0.05). Protein kinase analysis also showed that EtOH caused a time-dependent decrease of epidermal growth factor-stimulated autophosphorylation of epidermal growth factor receptor protein (180 kDa) during three feeding periods. Western blot analysis, using anti-tyrosine phosphorylated epidermal growth factor receptor (active form) antibody, revealed a major immunoreactive protein band (180 kDa) in all samples pre-incubated with 1 microM epidermal growth factor. Consistent with data from kinase analysis, treatment of EtOH decreased the immunoreactivity of the active form of epidermal growth factor receptor (180 kDa) in the stomach. In conclusion, EtOH feeding caused a time-dependent alteration of epidermal growth factor receptor in the stomach, which may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.

Animals↗

Transcriptional induction of cholesterol 7alpha-hydroxylase by dexamethasone in L35 hepatoma cells requires sulfhydryl reducing agents.

It is known that hepatic levels of reduced glutathione correlate with the activity of the liver-specific enzyme cholesterol-7alpha-hydroxylase. We examined the possibility that sulfhydryl reducing agents activate transcription of cholesterol 7alpha-hydroxylase. Adding dithiothreitol (DTT, 1 mM) and dexamethasone to L35 hepatoma cells increased the content of 7alpha-hydroxylase mRNA 3-fold above the levels observed with dexamethasone alone. Without dexamethasone, DTT had no affect. The addition of reduced glutathione to L35 cells demonstrated a similar potentiation of expression dependent on dexamethasone. Nuclear run-on assays showed that in the presence of both dexamethasone and DTT, the transcription of the 7alpha-hydroxylase gene was clearly increased. In contrast, by itself, dexamethasone did not cause a detectable increase in the transcription of the 7alpha-hydroxylase gene. Dexamethasone and DTT did not affect the transcription of beta-actin, suggesting a selective induction of the 7alpha-hydroxylase gene. DTT reversed repression of 7alpha-hydroxylase expression by insulin but not the repression by phorbol ester. Our data show for the first time that the sulfhydryl redox potential of the hepatocyte (i.e. level of reduced glutathione) has a marked influence on the transcription and expression of the liver-specific gene 7alpha-hydroxylase.

Animals↗

Incidence of NIDDM and the effects of gender, obesity and hyperinsulinaemia in Taiwan.

Our aim is to determine non-insulin-dependent diabetes mellitus (NIDDM) incidence in Taiwan and examine its relation to obesity and hyperinsulinaemia in Chinese men and women. A total of 995 men and 1195 women aged 35-74 years free from diabetes in two townships in Taiwan were followed up with a second examination. At baseline general and metabolic data were recorded, and detailed anthropometric parameters and plasma glucose and insulin were assessed. World Health Organisation (WHO) criteria of fasting glucose 7.8 mmol/l or greater was utilized for defining diabetes. The age-standardized incidence rate based on the United States population in 1970 was 9.3/1000 (CI 5.8-12.8) in men and 9.3/1000 (CI 6.2-12.4) in women and the based on the WHO population in 1976 was 8.9/1000 (CI .5-12.3) in men and 8.9/1000 (CI 5.9-11.9) in women for the Chinese who had a mean BMI slightly greater than 24 (kg/m2). The predictability of the plasma glucose level was greater than that of the insulin level and the obesity indices. NIDDM incidence increased approximately threefold with each 0.67 mmol/l increase in plasma glucose level in men and women. The present study demonstrated the essential relationship of not only BMI but also central obesity indices (such as subscapular and waist circumference) to the incidence of NIDDM among men and women and a stronger relationship between NIDDM incidence and obesity in women than in men. The predictive effects of obesity indices and fasting plasma insulin values on NIDDM risk were independent of each other in men. Obesity and hyperinsulinaemia each without the presence of the other can lead to an increased risk of NIDDM. In women the NIDDM incidence increased more than additively in those with both obesity and hyperinsulinaemia compared to those with single obesity or hyperinsulinaemia. A slightly higher incidence of NIDDM in Taiwan than in western countries was found. The importance of obesity is indicated for predicting NIDDM in the community. Hyperinsulinaemia was found to play a significant role in predicting NIDDM incidence independent of obesity in men and synergistically with obesity in women.

Adult↗

The large ribosomal protein gene cluster of a cryptomonad plastid: gene organization, sequence and evolutionary implications.

The complete sequence of the major ribosomal protein gene cluster of the plastid genome of the cryptomonad alga Guillardia theta (formerly Cryptomonas phi) is presented. The ribosomal protein genes (corresponding to the S10, spc, alpha and L13/S9 operons of E. coli) are found upstream of the previously reported plastid str operon, and transcribed in the same orientation. The genes are very tightly packed with as little as two nucleotides between the rpl14 and rpl24 genes. The gene arrangement is very similar to that reported for the rhodophyte alga, Porphyra purpurea, and the chromophyte diatom, Odontella sinensis, indicating a close evolutionary relationship between these groups of algae. Northern analysis indicates that the 29 genes are arranged as one operon and are transcribed as a single mRNA that is subsequently processed into smaller transcripts.

Amino Acid Sequence↗

Purification and characterization of two bifunctional chitinases/lysozymes extracellularly produced by Pseudomonas aeruginosa K-187 in a shrimp and crab shell powder medium.

Two extracellular chitinases (FI and FII) were purified from the culture supernatant of Pseudomonas aeruginosa K-187. The molecular weights of FI and FII were 30,000 and 32,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 60,000 and 30,000, respectively, by gel filtration. The pIs for FI and FII were 5.2 and 4.8, respectively. The optimum pH, optimum temperature, pH stability, and thermal stability of FI were pH 8, 50 degrees C, pH 6 to 9, and 50 degrees C; those of FII were pH 7, 40 degrees C, pH 5 to 10, and 60 degrees C. The activities of both enzymes were activated by Cu2+; strongly inhibited by Mn2+, Mg2+, and Zn2+; and completely inhibited by glutathione, dithiothreitol, and 2-mercaptoethanol. Both chitinases showed lysozyme activity. The purified enzymes had antibacterial and cell lysis activities with many kinds of bacteria. This is the first report of a bifunctional chitinase/lysozyme from a prokaryote.

Amino Acids↗

Cholesterol 7alpha-hydroxylase influences the expression of hepatic apoA-I in two inbred mouse strains displaying different susceptibilities to atherosclerosis and in hepatoma cells.

C57BL/6 mice are susceptible to diet-induced atherosclerosis, whereas BALB/c mice are resistant. The susceptibility of C57BL/6 mice has been linked to decreased plasma HDL cholesterol in response to a diet containing fat, cholesterol, and cholic acid. Feeding C57BL/6 mice a diet consisting of fat and cholesterol, but no cholic acid, increased plasma high density lipoprotein (HDL) cholesterol. The increase in HDL was associated with increases in both plasma apolipoprotein (apo)A-I and hepatic apoA-I mRNA. Supplementation of the cholesterol-rich diet with cholic acid inhibited the stimulatory effect of cholesterol on hepatic apoA-I mRNA expression, resulting in similar hepatic apoA-I mRNA levels compared to chow-fed mice. Atherosclerosis-resistant BALB/c mice were also resistant to diet-induced changes in plasma HDL, apoA-I, and hepatic apoA-I mRNA levels. Previous studies showed that the diets changed both the activity and mRNA encoding the liver specific enzyme 7alpha-hydroxylase (1993.J. Lipid Res. 34: 923-931). In both strains of mice, hepatic expression of apoA-I and 7alpha-hydroxylase mRNA varied in parallel. Whereas susceptible C57BL/6 mice also showed a significant correlation between HDL cholesterol and expression of 7alpha-hydroxylase, no such correlation was observed in BALB/c mice, suggesting that genetic differences in HDL metabolism, not hepatic apoA-I synthesis, are responsible for the strain specific differences in plasma HDL levels. The finding that lecithin: cholesterol acyltransferase (LCAT) activity was significantly decreased in C57BL/6 mice, but not in BALB/ c mice fed the atherogenic diet, further supports this conclusion. Additional studies show that McArdle hepatoma cells stably expressing plasmid-derived rat 7alpha-hydroxylase recapitulated the parallel linear relationship between 7alpha-hydroxylase and apoA-I mRNA expression observed in both strains of mice. These data link hepatic apoA-I mRNA expression to hepatic cholesterol/bile acid metabolism.

Animals↗

Production of chitinase from shellfish waste by Pseudomonas aeruginosa K-187.

The production of chitinolytic enzyme by Pseudomonas aeruginosa K-187, using shrimp and crab shell powder (SCSP) as the carbon source, was studied. It was observed that chemically treated SCSP induced a significant increase of enzyme production, as compared with untreated SCSP. Spent HCl and NaOH from the chitin production industry was used to process SCSP. Various strategies of SCSP processing are examined and compared in terms of chitinolytic enzyme production. A three-and-one-half-fold increase of enzyme production (0.68 U/ml to 2.4 U/ml) was attained using HCl/NaOH treated SCSP. The microorganism (K-187) was isolated from soil in Taiwan and has been characterized and reported in a previous paper.

Acetylglucosamine↗

Effects of in vivo treatments of nicotine and benzo[a]pyrene on the epidermal growth factor receptor in hamster buccal pouch.

This study was conducted to investigate the effects of two major ingredients in cigarette smoke, benzo-alpha-pyrene (BP) and nicotine (Nic), on epidermal growth factor (EGF) receptor in hamster buccal pouch. Adult male Syrian hamsters were treated by apically swabbing the buccal pouch with mineral oil (Control), 0.5 microgram/ml of BP, Nic or BP+Nic in mineral oil, twice a day, 5 days a week for 4 weeks. The BP+Nic treatment resulted in a significant reduction of submandibular gland (SG) EGF (Control vs. BP+Nic, 6.93 +/- 1.31 vs. 4.77 +/- 0.26* ng/g wet tissue, mean +/- S.D., n=5,*P < 0.05). Treatment with BP or Nic also caused a reduction, although not statistically significant, of EGF in SG extract. For the receptor study, all treatments significantly increased [125I]EGF binding to membrane preparations of buccal pouch as compared to Control (Control, BP, Nic, BP+Nic; 12.2 +/- 0.9, 20.5 +/- 2.2*, 17.0 +/- 1.3*, 21.2 +/= 1.6* fmol/mg prot. (mean +/- S.E.M.), n=5, P < 0.05). Scatchard analysis revealed that the higher EGF binding to the BP+Nic-treated sample was due to the higher number of receptors, but not higher affinity. Data from protein kinase study indicate that EGF stimulated phosphorylation of 170- and 150-kDa proteins in buccal membrane preparations. Treatment of BP+Nic resulted in reductions in EGF-stimulated phosphorylation of 170- and 150-kDa proteins by 19 and 72%, respectively. The present study has established an animal model which will benefit investigation of the mechanism by which tobacco alters the EGF receptor in oral buccal mucosa.

Animals↗

Benzo[a]pyrene and nicotine alter prostaglandin E2 receptor and its functions in hamster buccal mucosa.

This study investigated the in vivo effect of benzo[a]pyrene (BP) and nicotine (NC) on prostaglandin E2 (PGE2) receptor and its cellular responses in hamster buccal mucosa. Adult male Syrian hamsters were treated by apical swabbing the pouch with mineral oil (control), or 1 mM BP + NC, twice/day, 3 times/week, for 8 weeks. The BP + NC treatment significantly decreased the specific binding of PGE2 to buccal mucosal membranes (12.8 +/- 0.14 vs 8.7 +/- 1.13 fmol/mg protein; control vs. BP + NC; mean +/- S.D., n=6, P < 0.05). Scatchard analysis revealed that the reduction of receptor binding might be due to an alteration of the receptor binding properties, such as increase of the dissociation constant (Kd, 1.08 vs. 4.20 nM; control vs. BP + NC) and elimination of the low-affinity binding site. The addition of 16,16-dimethyl PGE2 (DMPGE2) into the control buccal tissue caused a 36% decrease of the overall protein synthesis. In contrast, DMPGE2 enhanced the [35S]methionine incorporation into several major proteins (i.e., 150, 120, 90, 75, 55, 38 and 26 kDa) in the BP + NC group. DMPGE2 showed no effect on DNA synthesis in both groups. Our data demonstrated that BP + NC in vivo altered PGE2 receptor properties and cellular functions in hamster buccal pouch.

16,16-Dimethylprostaglandin E2↗

Epidermal growth factor in gingival crevicular fluid and its binding capacity in inflamed and non-inflamed human gingiva.

Epidermal growth factor (EGF) is a pro-inflammatory small peptide (6000 Da) with a variety of biological activities including stimulation of cell differentiation and mediation of proteolysis by binding to its specific receptor on the cell surface. The purpose of this study was to determine the levels of EGF in gingival crevicular fluid (GCF) and the EGF-binding capacity to its receptor in gingival tissue. The GCF samples were collected from six patients by inserting paper strips into shallow (< 5 mm) and deep pockets (> or = 5 mm) for 30 s. The strips were soaked in 0.2 M acetate for extraction and the EGF in the supernatants was analysed by radioimmunoassay. To determine the binding capacity of EGF to its receptor, inflamed gingival tissues (pocket depth > or = 5 mm, Gingival Index = 1, 2 or 3) were collected during periodontal flap surgery and non-inflamed gingival tissues (pocket depth < 5 mm, Gingival Index = 0) were collected during surgical "crown lengthening' for aesthetic purposes. The tissues were pooled by group, homogenized for membrane preparation and the supernatants obtained after centrifugation were used in a 125IEGF binding assay. To determine the effect of inflammation on gingival EGF receptor, inflamed and non-inflamed gingival tissues were collected from six patients and prepared similarly to the binding assay. Gingival preparations were then electrophoresed for Western blot analysis with EGF receptor antiserum. The EGF level in GCF was significantly lower (P < 0.05) in the samples collected from pockets > or = 5 mm (0.9 +/- 0.6 ng/ml) than in those from pockets < 5 mm (2.4 +/- 2.1 ng/ml). The average Gingival Index was higher (2.6 +/- 0.6) in pockets > or = 5 mm than in pockets < 5 mm (1.4 +/- 1.0). Specific binding of 125I-EGF to its receptor in inflamed gingiva was 2.7-fold higher than in non-inflamed gingiva (14.4 +/- 4.9 vs 5.4 +/- 1.8 fmol/g wet tissue). Western blot analysis showed two major immunoreactive bands (180 and 120 kDa), which represent EGF receptor and its degradation products, in inflamed gingiva. The findings show that inflammation activates EGF binding capacity in gingiva and that the up-regulation of EGF receptor in inflamed gingiva might be associated with a lowered concentration of EGF in GCF produced adjacent to inflamed gingiva. This up-regulation of EGF receptor during inflammation might be an important mechanism in the pathogenesis of periodontal disease.

Blotting, Western↗

Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes.

Codeine and morphine pharmacokinetics among different CYP2D6 genotypes was compared in this study. Polymerase chain reaction tests were used to determine CYP2D6 genotypes in leukocyte deoxyribonucleic acid in 32 unrelated volunteers. Based on the genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 8), heterozygous C/T188 (n = 12), and homozygous T/T188 (n = 12). Each subject was given a single oral dose of 30 mg codeine phosphate tablet after overnight fasting. Plasma concentration of codeine and 24-hour urinary morphine recovery were measured with HPLC. All three genotypes of subjects showed almost identical time profiles of plasma codeine. Urinary morphine glucuronide was hydrolyzed with beta-glucuronidase. The total recovered amount of morphine and glucuronides was 4349 +/- 646, 2564 +/- 242, and 1127 +/- 164 nmol (mean +/- SEM), respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The significant lower amount of urinary morphine but identical codeine plasma concentration suggested a lower partial clearance of the formation of morphine from codeine in T/T188 subjects. The results suggest a future study to assess the analgesic effect of codeine in different genotypes of CYP2D6 extensive metabolizers.

Adult↗

Detection of epidermal growth factor receptor in inflammatory periapical lesions.

Epithelial cell proliferation is often observed in periapical lesions of endodontic origin. The mechanisms which stimulate the epithelial cell rests of Malassez to proliferate are not understood fully. Fifteen inflammatory periapical lesions (10 granulomas and five cysts) obtained from periapical surgery and six additional periapical lesions (four granulomas and two cysts) collected from extracted teeth were examined using immunohistochemical staining and 125I-EGF (epidermal growth factor) binding assay to detect the presence of epidermal growth factor receptor. The results indicated that the periapical lesions without epithelial cell proliferation had a weak immunoperoxidase staining or low specific binding of 125I-EGF. In contrast, the periapical lesions with epithelial cell proliferation and cyst formation exhibited a strong immunoperoxidase staining in the epithelial cells or high specific binding of 125I-EGF.

Epidermal Growth Factor↗