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Martin Wagner

Publications and source records attributed to Martin Wagner.

At least 55 records · Page 3Linked to original sources
PubMed2003

Standardization of diagnostic PCR for the detection of foodborne pathogens.

In vitro amplification of nucleic acids using the polymerase chain reaction (PCR) has become, since its discovery in the 1980s, a powerful diagnostic tool for the analysis of microbial infections as well as for the analysis of microorganisms in food samples. However, despite its potential, PCR has neither gained wide acceptance in routine diagnostics nor been widely incorporated in standardized methods. Lack of validation and standard protocols, as well as variable quality of reagents and equipment, influence the efficient dissemination of PCR methodology from expert research laboratories to end-user laboratories. Moreover, the food industry understandably requires and expects officially approved standards. Recognizing this, in 1999, the European Commission approved the research project, FOOD-PCR (http://www.PCR.dk), which aims to validate and standardize the use of diagnostic PCR for the detection of pathogenic bacteria in foods. The present review focuses on the harmonization procedure and standardization criteria for detection of foodborne pathogens by PCR. The progress of standardization so far and future perspectives of diagnostic PCR are discussed.

Bacteria↗
PubMed2003

3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) as positron emission tomography tracer for imaging proliferation in a murine B-Cell lymphoma model and in the human disease.

Here we describe the evaluation of 3'-[(18)F]fluoro-3'-deoxythymidine [[(18)F]-FLT] as a tracer for positron emission tomography (PET) in a murine model of B-cell lymphoma and in human malignant lymphoma. The human B-cell line DoHH2 expressed high levels of active thymidine kinase 1 (TK-1) as the key enzyme of [(18)F]-FLT metabolism. Immunostaining confirmed high levels of TK-1 in DoHH2 derived xenograft tumors in SCID/SCID mice. In vitro studies demonstrated a time-dependent uptake of [(18)F]-FLT, an efficient phosphorylation to the respective monophosphate and the incorporation of [(18)F]-FLT into the perchloric acid insoluble fraction in DoHH2 cells, indicating the incorporation of this tracer into the DNA. After incubation with [(18)F]FLT for 240 min, 12.5% +/- 1.0% of radioactivity applied to the medium was intracellularly trapped in DoHH2 cells. Specific accumulation of [(18)F]-FLT in the malignant cell clone was confirmed in biodistribution studies in SCID/SCID mice bearing DoHH2-derived tumors. The percentage of injected dose of [(18)F]-FLT per gram of tumor tissue correlated with the tumor-proliferation index as evaluated in BrdUrd-labeling experiments. In a pilot study of 11 patients with both indolent and aggressive lymphoma, [(18)F]-FLT was suitable and comparable to [(18)F]-FDG in the ability to detect malignant lesions by PET scan. Furthermore, we found a close correlation (r = 0.95, P < 0.005) of the [(18)F]-FLT standardized uptake values with the Ki67-labeling index of tissue biopsies (n = 10) in these patients. These results suggest that [(18)F]-FLT represents a novel tracer for PET that enables imaging of proliferation in human lymphoma in vivo.

Animals↗
PubMed2003

Characterization of Listeria monocytogenes recovered from 41 cases of sporadic listeriosis in Austria by serotyping and pulsed-field gel electrophoresis.

41 clinical Listeria monocytogenes strains recovered from seven feto-maternal and 34 non-pregnancy associated cases of human listeriosis documented between 1997 and 2000 underwent serotyping and typing by pulsed-field gel electrophoresis (PFGE) applying the enzymes AscI, ApaI and SmaI. The pulsotypes of the clinical strains were compared to the pulsotypes of three L. monocytogenes strains isolated from healthy fecal carriers and nine reference strains isolated from seven outbreaks in Europe and the USA. The 41 clinical strains of Austrian provenance showed 37 pulsotypes. Five sets of two Austrian strains each were indistinguishable by PFGE typing. Epidemiological links were absent between these indistinguishable isolates. One unique pulsotype (AB) was found in three fecal isolates. Five pulsotypes (A, Q, R, AC and AD) were distinguished among the strains associated with outbreaks. Clusters consisting of two, five and six Austrian strains each were indistinguishable from the outbreak-associated pulsotypes A, Q and R, respectively, after PFGE analysis with AscI. Three strains of AscI pulsotype Q and five strains of AscI pulsotype R could be further differentiated by restriction with ApaI and SmaI. One strain each from sporadic cases shared a combined pulsotype with the outbreak strains of pulsotypes A and R, respectively. These PFGE data suggest that a similar genetic background can be found in strains which have been contributing to outbreaks world-wide and in isolates associated with sporadic listeriosis in Austria.

Adult↗
PubMed2003

Nucleic acid-based, cultivation-independent detection of Listeria spp and genotypes of L monocytogenes.

Based on comparative analysis of 16S rRNA gene sequences, two oligonucleotide probes for in situ detection of all members of the genus Listeria were designed. These probes allowed fast and reliable in situ detection of Listeria spp. even in complex samples like raw milk. Almost full-length iap (invasion-associated protein) gene sequences were determined for 69 Listeria monocytogenes strains of all 13 known serotypes. A comparison of these sequences revealed that the L. monocytogenes strains can be grouped into three distinct genotypes. These clusters correlate well with distinct serotypes. Thus, strains of serotypes b and d belong to genotype I, a and c to genotype II, and 4a and 4c, which are rarely isolated from humans, group together within genotype III. These results could be corroborated by further comparative sequence analysis of genes encoding two phospholipases - plcA and plcB. Based on the iap gene sequences, a highly specific and reproducible competitive PCR detection method was developed. Primer pairs targeting genotype-specific regions of the iap gene were designed. The amplification of non-specific PCR products from DNA of non-target strains was prevented by adding competitive primers. By applying this method, the rapid and reliable distinction of the three L. monocytogenes genotypes was possible.

Animals↗
PubMed2003

A simple method for the differentiation of Listeria monocytogenes based on induction of lecithinase activity by charcoal.

The PlcB phospholipase C, or lecithinase, is an important listerial virulence factor of potential use as a pathogenicity marker for Listeria spp. food isolates. However, wild-type strains of Listeria monocytogenes express virulence factors very poorly in vitro and their lecithinase activity is normally difficult to detect on agar plates. We recently reported that the production of listerial virulence factors is strongly induced if L. monocytogenes is grown in the presence of activated charcoal. We report here a simple method for the rapid differentiation of L. monocytogenes from other Listeria spp. based on a comparison of lecithinase reactions in egg yolk agar plates with and without charcoal supplementation. All L. monocytogenes wild-type isolates tested showed a clear induction of lecithinase activity in charcoal-supplemented medium (CEYM), while nonpathogenic Listeria spp. remained negative in CEYM. The animal pathogen L. ivanovii was easily differentiated from L. monocytogenes because it showed a strong lecithinase reaction independently of the presence or absence of charcoal in the medium.

Charcoal↗
PubMed2003

Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells.

Mouse embryonic stem (ES) cells differentiate into cells of all three primary germ layers including endodermal cells that produce insulin in vitro. We show that constitutive expression of Pax4 (Pax4(+)), and to a lesser extent Pdx1 (Pdx1(+)), affects the differentiation of ES cells and significantly promote the development of insulin-producing cells. In Pax4 overexpressing R1 ES cells, isl-1, ngn3, insulin, islet amyloid polypeptide, and glucose transporter 2 (Glut-2) mRNA levels increase significantly. The number of nestin-expressing (nestin+) cells also increases. Constitutive Pax4 expression combined with selection of nestin+ cells and histotypic culture conditions give rise to spheroids containing insulin-positive granules typical of embryonal and adult beta cells. In response to glucose, Pax4(+) and wild-type ES-derived cells release insulin. Transplantation of these cells into streptozotocin-treated diabetic mice results in a normalization of blood glucose levels. We conclude that constitutive expression of Pax4 in combination with histotypic cultivation facilitates ES cell differentiation into the pancreatic lineage, which leads to the formation of islet-like spheroid structures that produce increased levels of insulin.

Animals↗
PubMed2003

Transgenic overexpression of the oncofetal RNA binding protein KOC leads to remodeling of the exocrine pancreas.

BACKGROUND & AIMS: To elucidate the function of the oncofetal RNA-binding protein, K-homologous (KH) domain containing protein overexpressed in cancer (KOC), we studied the effect of a constitutive reexpression of KOC in transgenic mice. METHODS: Transgenic mouse lines expressing KOC under the control of the mouse metallothionein promoter were generated and were shown to express the 69-kilodalton protein. Two mouse lines with moderate to strong gene expression of the transgene were further analyzed. RESULTS: The pancreas of KOC-transgenic mice showed progressive morphologic alterations, including an increased proliferation of acinar cells, acinar-ductal metaplasia, net loss of acinar tissue, and the appearance of numerous interstitial cells. Acinar-ductal metaplasia led to the development of duct-like structures exhibiting the characteristics of normal intralobular ducts. Interstitial cells expressed markers of endocrine or ductal differentiation. Nerve growth factor alpha (NGF-alpha) and the GTPase kir/Gem were identified as potential targets of KOC by expression profiling analyses. CONCLUSIONS: Reexpression of KOC in the transgenic model is apparently incompatible with the maintenance of a fully differentiated, adult acinar phenotype and may lead to a more fetal ductal phenotype via acinar-ductal metaplasia. This and the appearance of interstitial cells with a ductal and endocrine differentiation capacity suggest that transgenic reexpression of the oncofetal gene KOC may recapitulate a developmental program active during embryogenesis.

Animals↗
PubMed2003

Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice.

BACKGROUND & AIMS: Cholestasis induces changes in hepatic adenosine triphosphate-binding cassette (ABC) transporter expression. We aimed to investigate the role of the nuclear bile acid receptor (farnesoid X receptor [FXR]) in mediating changes in ABC transporter expression and in determining liver injury. METHODS: Hepatic ABC transporter (multidrug resistance-associated proteins [Mrp] 2-4 and bile salt export pump [Bsep]) expression and localization were studied in common bile duct-ligated (CBDL) FXR knockout (FXR(-/-)), wild-type (FXR(+/+)), and sham-operated mice. Serum alanine aminotransferase, alkaline phosphatase, bilirubin and bile acid levels, hepatic bile acid composition, and liver histology were investigated. Cholangiomanometry and bile duct morphometry were performed. RESULTS: CBDL induced expression of Mrp 3 and Mrp 4 in FXR(+/+) and even more in FXR(-/-), whereas Mrp 2 expression remained unchanged. Bsep expression was maintained in CBDL FXR(+/+) but remained undetectable in CBDL FXR(-/-). Alanine aminotransferase levels and mortality rates did not differ between CBDL FXR(+/+) and FXR(-/-). CBDL increased biliary pressure and induced bile ductular proliferation and bile infarcts in FXR(+/+), whereas FXR(-/-) had lower biliary pressures, less ductular proliferation, and developed disseminated liver cell necroses. CONCLUSIONS: Overexpression of Mrp 3 and Mrp 4 in CBDL mice is FXR independent and could play an important role in the adaptive hepatic ABC transporter response to cholestasis. Maintenance of Bsep expression strictly depends on FXR and is a critical determinant of the cholestatic phenotype. Lack of bile infarcts in CBDL FXR(-/-) suggests that development of bile infarcts is related to bile acid-dependent bile flow and biliary pressure. This information is relevant for the potential use of FXR modulators in the treatment of cholestatic liver diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Application of single-strand conformation polymorphism and denaturing gradient gel electrophoresis for fla sequence typing of Campylobacter jejuni.

Campylobacter jejuni is a frequent cause of bacterial gastroenteritis in humans all over the world. Several molecular typing methods are used to study the epidemiology of Campylobacter spp. infections. The aim of the present study was to investigate the application of single-strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) analysis as rapid primary subtyping methods for C. jejuni. A variable fragment from the 3' end of the flaA to the 3' end of the intergenic region, separating the flaA and flaB genes, was subjected to SSCP and DGGE analysis. A total of 48 clinical C. jejuni isolates, 49 C. jejuni strains isolated from poultry, 2 strains isolated from ducks and 1 strain isolated from a pheasant were assigned to 24 distinct SSCP patterns. Sequence analysis of the respective DNA fragments revealed that every different fla sequence type could be distinguished by SSCP. DGGE proved to be equally discriminatory. Both methods can be applied as primary subtyping methods, because pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) analysis further differentiated isolates belonging to the same fla sequence types.

Bacterial Typing Techniques↗
PubMed2003

Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine.

BACKGROUND/AIMS: Adaptive changes in transporter expression in liver and kidney provide alternative excretory pathways for biliary constituents during cholestasis and may thus attenuate liver injury. Whether adaptive changes in ATP-binding cassette (ABC) transporter expression are stimulated by bile acids and their nuclear receptor FXR is unknown. METHODS: Hepatic, renal and intestinal ABC transporter expression was compared in cholic acid (CA)- and ursodeoxycholic acid (UDCA)-fed wild-type (FXR(+/+)) and FXR knock-out mice (FXR(-/-)). Expression was assessed by reverse transcription-polymerase chain reaction, immunoblotting and immunofluorescence microscopy. RESULTS: CA feeding stimulated hepatic Mrp2, Mrp3, Bsep and renal Mrp2 as well as intestinal Mrp2 and Mrp3 expression. Lack of Bsep induction by CA in FXR(-/-) was associated with disseminated hepatocyte necrosis which was not prevented by compensatory induction of Mrp2 and Mrp3. With the exception of Bsep, UDCA stimulated expression of hepatic, renal and intestinal ABC transporters independent of FXR without inducing liver toxicity. CONCLUSIONS: Toxic CA and non-toxic UDCA induce adaptive ABC transporter expression, independent of FXR with the exception of Bsep. Stimulation of hepatic Mrp3 as well as intestinal and renal Mrp2 by UDCA may contribute to its therapeutic effects by inducing alternative excretory routes for bile acids and other cholephiles.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Hemolytic-uremic syndrome associated with enterohemorrhagic Escherichia coli O26:H infection and consumption of unpasteurized cow's milk.

BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) O26 has emerged as a significant cause of hemolytic-uremic syndrome (HUS). The source and the vehicle of contamination with EHEC O26 are not often identified. We report two Austrian cases of HUS due to E. coli O26:H- affecting an 11-month-old boy and a 28-month-old girl in which transmission through unpasteurized cow's milk was positively identified. METHODS AND RESULTS: Using automated ribotyping and pulsed-field gel electrophoresis (PFGE), the isolates (which yielded the virulence genes stx2, eae, and hly) were indistinguishable from each other. An epidemiologic investigation revealed that the children had stayed in the same hotel. Both patients had consumed unpasteurized cow's milk from the breakfast buffet. Fecal samples were taken from the cows of the farm producing the incriminating milk, and one of three cattle EHEC O26:H- isolates had a PFGE pattern indistinguishable from that of the patients' strains. CONCLUSIONS: These two cases of E. coli O26 infection illustrate the hazards associated with the consumption of raw milk, and underline the importance of microbiological diagnostic approaches able to detect sorbitol-fermenting, non-O157 EHEC.

Animals↗
PubMed2003

A case of sporadic ovine mastitis caused by Listeria monocytogenes and its effect on contamination of raw milk and raw-milk cheeses produced in the on-farm dairy.

We describe a case of listerial mastitis in a flock of 130 sheep. The animals were housed at a farm where the bulk raw ewe milk was processed to produce raw milk soft cheese. List. monocytogenes was shed from the right mammary complex. Shedding was observed over a period of 99 d. A mean level of 4-56 x 10(4) cfu (colony forming units) Listeria monocytogenes/ml was recovered from the raw milk originating from the infected udder. The numbers ranged from 9 x10(1) to 2.95 x 10(5). The bulk milk was contaminated by approx. 5.7 x 10(3) cfu/ml. In the cheese product, 2.0 x 10(2) cfu List. monocytogenes/g were constantly detectable for a period of 7 d post manufacture. The starter culture used for coagulation had a pivotal influence on the behaviour of List. monocytogenes during cheesemaking. Using the same mesophilic buttermilk culture as used by the farmer allowed numbers of Listeria to increase 60-fold within 12 h owing to a delayed acidification of the bulk milk. Addition of a thermophilic yogurt culture reduced the numbers of Listeria within 8 h of incubation.

Animals↗
PubMed2003

Successful conservative management of acute hepatic failure following exertional heatstroke.

Acute hepatic failure is a rare complication of exertional heatstroke with poor prognosis. We herein report a 24-year-old man presenting with acute hepatic failure and rhabdomyolysis following exertional heatstroke during hard physical work on a construction site. Acute hepatic failure occurred after 2 days and led to massive impairment of coagulation parameters. On day 3 after heatstroke the patient fulfilled standard criteria for emergency liver transplantation (i.e. the 'London criteria' and the 'Clichy criteria') but was not transplanted. Nevertheless liver function improved spontaneously thereafter and the patient recovered completely within 12 days. In contrast, the outcome of emergency liver transplantation was dismal in three cases of exertional heatstroke in the literature. Thus conservative management appears to be justified in heatstroke-associated liver failure even in the presence of accepted criteria for emergency liver transplantation.

Adult↗
PubMed2002

IGF-I and TGF-beta1 application by a poly-(D,L-lactide)-coated cage promotes intervertebral bone matrix formation in the sheep cervical spine.

STUDY DESIGN: A sheep cervical spine interbody fusion model was used to determine the effect of combined insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta1) applied by a poly-(D,L-lactide) (PDLLA)-coated cage. OBJECTIVES: The purpose of this study was to determine the effect of a new PDLLA carrier system, and to evaluate the effect of combined IGF-I and TGF-beta1 application in a sheep cervical spine model. SUMMARY AND BACKGROUND DATA: Growth factors such as bone morphogenic protein-2 have been shown to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum growth factor for promoting spinal fusion and the optimum method for delivering such growth factors are still a matter of discussion. METHOD: In this study, 32 sheep underwent C3-C4 discectomy and fusion: Group 1 (autologous tricortical iliac crest bone graft; n = 8), Group 2 (titanium cage; n = 8), Group 3 (titanium cage coated with a PDLLA carrier; n = 8), and Group 4 (titanium cage coated with a PDLLA carrier including IGF-I [5% w/w] and TGF-beta1 [1% w/w; n = 8). Blood samples, body weight, and body temperature were analyzed. Radiographic scans were performed before and after surgery, then at 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, the disc space height, intervertebral angle, and lordosis angle were measured. After 12 weeks, the animals were killed, and fusion sites were evaluated using functional radiographic views of the animals in flexion and extension. Quantitative computed tomographic scans were performed to assess bone mineral density, bone mineral content, and bony callus volume. Biomechanical testing of the motion segment C3-C4 was performed in flexion, extension, axial rotation, and lateral bending. The stiffness, range of motion, neutral zone, and elastic zone were determined. Histomorphologic and histomorphometric analysis was performed, and polychrome sequential labeling was used to determine the time frame of new bone formation. RESULTS: There were no differences between the groups in terms of blood counts, body weight, and temperature. Over a 12-week period, cage Groups 2 to 4 showed significantly higher values for the intervertebral angle than for the bone graft. Functional radiographic assessment showed significantly lower residual flexion-extension movement in Group 4 than in any other group. The PDLLA-coated cages with IGF-I and TGF-beta1 showed significantly higher values for bone mineral density, bone mineral content, and bony callus volume. The average stiffness in rotation and bending was significantly higher, and the range of motion, neutral zone, and elastic zone in rotation were significantly lower in Group 4 than in any other group. Although only one animal in Group 4 demonstrated solid bony fusion after 12 weeks, histomorphometric evaluation showed a more progressed bone matrix formation in the group that had PDLLA-coated cages with IGF-I and TGF-beta1 than in any other group. Polychrome sequential labeling showed accelerated intervertebral bone matrix formation in Group 4. CONCLUSIONS: The findings showed that PDLLA coating of cervical spine interbody fusion cages as a delivery system for growth factors was effective. Although IGF-I and TGF-beta1 application by a PDLLA-coated interbody cage was not able to achieve solid bony fusion during the 12-week follow-up period, these growth factors significantly increased the results of interbody bone matrix formation. Additional longer-term studies are required to determine whether combined IGF-I and TGF-beta1 application leads to a successful spinal fusion.

Absorbable Implants↗
PubMed2002

Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines.

Here we report the expression of major pyrimidine metabolising enzymes in pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic cancer and the in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT). The expression of pyrimidine metabolising enzymes was evaluated with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1) activity was measured with a fluorocytometric assay. The cellular uptake and intracellular metabolism of [(18)F]FLT were evaluated in pancreatic lobules and in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were increased in six pancreatic cancer cell lines, while mRNA levels of thymidine kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human pancreatic cancer as compared with normal pancreatic tissue and samples from patients with chronic pancreatitis. The cellular uptake of [(18)F]FLT was 18.4%+/-3.6% and 5.2%+/-1.4% of the applied radioactivity after 240 min in SW-979 and BxPc-3 cells, respectively, while uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) was only 0.6%+/-0.04% (SW-979) and 0.3%+/-0.13% (BxPc-3) after 240 min of incubation. In contrast, cellular uptake of [(18)F]FLT in isolated pancreatic lobules and growth-arrested HT1080 cells was lower as compared with the uptake of [(18)F]FDG and with the malignant pancreatic cancer cell lines. HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the phosphorylation of [(18)F]FLT to the respective monophosphate in both cell lines. Furthermore, 0.8%+/-0.12% (BxPc-3) and 1.3%+/-0.38% (SW-979) of the applied radioactivity was detected in the perchloric acid-insoluble cell fraction, indicating the incorporation of [(18)F]FLT into the DNA. Our results demonstrate the cellular uptake, intracellular trapping and incorporation into the DNA of [(18)F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme of [(18)F]FLT metabolism, is overexpressed in pancreatic cancer cell lines and in human pancreatic cancer. Thus, we propose [(18)F]FLT as a promising tracer for positron emission tomography that might overcome current limitations in the diagnosis of pancreatic cancer.

Base Sequence↗
PubMed2002

Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cells.

BACKGROUND & AIMS: The epidermal growth factor (EGF) receptor family and the corresponding ligands are frequently overexpressed in pancreatic cancer. To compare the biological effects of transforming growth factor (TGF)-alpha and amphiregulin (AR) on growth and differentiation of the exocrine pancreas, we have generated transgenic mice overexpressing AR under control of the elastase promoter. METHODS: Two independently generated transgenic mouse lines overexpress 50-, 43-, 28-, 26-, and 16-kilodalton AR forms in the pancreas. RESULTS: Morphologic and immunohistochemical examinations suggest that small intralobular duct and centro-acinar cells proliferate in response to AR in these mice. AR transgenic mice display increased Ras, Erk1/2, cyclin D/CDK4, and cyclin E/CDK2 activity and G1/S progression in pancreatic duct cells. In contrast to TGF-alpha transgenic mice, AR neither induced tubular complex formation nor elicited a strong fibrogenic response. AR induced a slight induction of ErbB2 on duct cells, whereas TGF-alpha resulted in overexpression of the EGF receptor in cells within tubular complexes. Furthermore, AR and TGF-alpha displayed different effects on differentiation of isolated acini in vitro comparable to the situation in vivo. CONCLUSIONS: These data suggest that AR induces a mitogenic response selectively in small duct cells through activation of Ras, CDK2, and CDK4, respectively. The closely related EGF receptor ligands, AR and TGF-alpha, display different biological effects when overexpressed in the exocrine pancreas in vivo.

Amphiregulin↗