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G Adler

Publications and source records attributed to G Adler.

At least 253 records · Page 14Linked to original sources
PubMed1996

Reduction of bile secretion by prostaglandins in the rat in vivo.

Bile secretion has been reported to be regulated by circulating hormones and by autonomic liver nerves. In the in situ perfused rat liver, prostaglandins reduce bile flow and bile acid secretion. The aim of this study was to investigate the regulation of bile secretion by prostaglandins in the in vivo situation. The bile duct and portal vein of anaesthetised Wistar rats were cannulated by polyethylene tubes. Bile flow was determined gravimetrically. Bile acids were quantified by the 3-alpha-hydroxy-steroid-dehydrogenase method and by high-pressure-liquid-chromatography (HPLC) separation. Administration of 1 microM prostaglandin F2 alpha into the portal vein over 5 minutes reduced bile flow from 1.57 microliter/min.g liver to 0.95 microliter/min.g liver and bile acids secretion from 148 to 81 nmol/100g/min. The administration of different doses (0.1 microM, 1 microM, 10 microM) of prostaglandin F2 alpha reduced hepatic bile secretion in a dose-dependent manner. Similar effects were observed after infusion of prostaglandin D2. However, the ratio of the bile acids (alpha-tauromuricholic acid), beta-tauromuricholic acid, taurocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid) was unchanged by prostaglandin F2 alpha. In conclusion, infusion of prostaglandin F2 alpha into the portal vein results in a reduction of bile flow and bile acid secretion in a dose-dependent manner. These results suggest that the effect is linked to canicular bile secretion.

Animals↗
PubMed1996

Anti-fucosyl-GM1 ganglioside IgG and IgM autoantibodies in human serum: no link to pathology.

Anti-fucosyl-GM1 ganglioside antibodies were detected in sera of five persons: four patients with autoimmune neuropathies and more recently, IgG antibodies in one with Graves' disease (Adler et al., Autoimmunity 18, 149-152, 1994) [1]. In the latter case, we were unable to find any relation between the occurrence of antibodies and thyroid disease. Now we report a detailed study on the anti-glycolipid antibodies in this patient. We found that her serum contained not only IgG but also a high level of anti-FucGM1 IgM antibodies, with a titer stable over a period of 5 years of treatment and follow-up. The carbohydrate structure of the epitope recognized by IgG and some of IgM antibodies seems to consist of Fuc-Gal-GalNAc-Gal- or a part of this sequence. Moreover, this patient's serum contained other IgM antibodies active against FucGM1 and also asialo GM1 glycolipids. Our results indicate that anti-FucGM1 ganglioside antibodies of G and M classes occur in serum of this patient with no apparent adverse health effects.

Antibody Specificity↗
PubMed1996

Effects of epinephrine on glucose metabolism in patients with alcoholic cirrhosis.

The cirrhotic liver has been shown to be resistant to the actions of various glucoregulatory hormones. The objective of this study was to investigate the effects of epinephrine on hepatic glucose metabolism in cirrhotic patients. Thirteen cirrhotic and eight healthy subjects were studied. Hepatic glucose production and turnover of alanine and glycerol were measured using stable isotope technique before and during 70 and 150 minutes of epinephrine infusion (0.1 microgram/kg/min). beta-Adrenoreceptor binding sites and affinity in mononuclear leukocyte membranes also were determined. Hepatic glucose production and alanine turnover in normals significantly increased during epinephrine infusion, but did not change in cirrhotics. Glycerol turnover increased after 70 minutes of epinephrine infusion in both groups. Epinephrine induced a significant rise of high-affinity beta-adrenoreceptor binding sites in normals, yielding a significant correlation between hepatic glucose production and receptor density (r = .94, P < .0001). In cirrhotic patients, similar changes in the number of high-affinity beta-adrenoreceptors were observed, but no correlation with hepatic glucose production was detected. The cirrhotic liver did not respond normally to the stimulatory effect of epinephrine on hepatic glucose production. Because this blunted response was not related to changes of beta-adrenoreceptors, our findings suggest that epinephrine resistance in cirrhosis was caused by a postreceptor defect.

Adult↗
PubMed1996

Clinical evaluation of the faecal elastase test in the diagnosis and staging of chronic pancreatitis.

OBJECTIVE: To test the diagnostic accuracy of faecal elastase (FE), a new test of exocrine pancreatic function, in a large prospective population of patients with abdominal complaints. METHODS: Between January 1994 and December 1995, 131 patients (age range 17-82 years) were submitted for exocrine pancreatic function testing. Sixty-three patients had a firm diagnosis of chronic pancreatitis (CP) at stage I-III according to endoscopic retrograde cholangiopancreatography (ERCP). Twenty patients suffered from other pancreatic diseases (PD), and 48 patients had various other gastrointestinal diseases (GD). Fifty-seven healthy controls (HC) were also investigated. Stool specimens were analysed for FE by enzyme-linked immunosorbent assay (ELISA) and for faecal chymotrypsin (FC). The pancreolauryl serum test (PLT) was also performed in 97 patients and 23 healthy controls. RESULTS: FE was 200; 45-500 micrograms/g (median; range) in CP-I (n = 19), 94; 0-400 micrograms/g in CP-II (n = 14) and 38; 0-135 micrograms/g in CP-III patients (n = 30). With a cutoff of 200 micrograms/g, abnormal test results were found in 47% of CP-I, 79% of CP-II and 100% of CP-III patients; in 30% of PD patients, in 38% of GD patients and in 7% of HC. Sensitivity of abnormal FE in diagnosing CP was 79% (FC: 48%; PLT: 71%). The specificity of only 62% (FC: 73%; PLT: 67%) in the GD group increased to 78% (FC: 81%; PLT: 77%) when patients with small bowel diseases and diarrhoea (n = 22) were excluded. CONCLUSION: Faecal elastase is more sensitive than chymotrypsin and comparable to the pancreolauryl test in the diagnosis of chronic pancreatitis. Indirect exocrine pancreatic function tests are not helpful to differentiate between pancreatic and small bowel diseases in a prospective population of patients with abdominal complaints.

Adolescent↗
PubMed1996

Effects of selective phosphodiesterase 3 inhibition in the perfused liver of the rat after endotoxin treatment.

1. This study was designed to investigate the role of rat phosphodiesterase 3 (RPDE3) in regulation of liver metabolism in sepsis. We studied the effects of the phosphodiesterase 3 inhibitor (PDI), enoximone, alone and in combination with regulating factors of hepatic carbohydrate metabolism and bile secretion in the perfused liver of rats treated 4 h earlier with endotoxin. In addition, cyclic AMP and cyclic GMP levels were determined in the effluate and bile by radio immunoassay methods. 2. After endotoxin treatment, infusion of enoximone at three concentrations (1 microM, 10 microM) resulted in an increased glucose output from -1.4 +/- 0.9 to 7.8 +/- 2.5 mumol l-1 20 min-1. Bile acid-independent bile flow increased also, in a dose-dependent manner. 3. In untreated livers, cyclic AMP release increased in the effluate from 1000 +/- 73 fmol g-1 min-1 to 1710 +/- 143 fmol g-1 min-1 when enoximone (10 microM) was administered. In bile from untreated livers, the level of cyclic AMP was also significantly increased by enoximone. After endotoxin treatment, the enoximone (10 microM) effect on cyclic AMP levels in effluate and bile was greatly reduced. Levels of cyclic GMP in the effluate and bile appeared unchanged in the presence of enoximone. 4. During co-infusion of glucagon (1 nM) and enoximone (10 microM), cyclic nucleotide levels in the effluate and bile of livers after endotoxin treatment were determined. In the effluate, cyclic AMP release increased from 827 +/- 144 fmol g-1 min-1 to 17802 +/- 2821 fmol g-1 min-1 when glucagon was administered. The presence of enoximone enhanced cyclic AMP further to 41696 +/- 920 fmol g-1 min-1. The same changes in cyclic AMP release were found in bile. Levels of cyclic GMP in the effluate and bile were not significantly affected by the administration of glucagon and the PDI. 5. Glucose release was determined during glucagon, sympathetic nerves stimulation and phenylephrine administration in the presence and absence of enoximone. The addition of enoximone to glucagon increased glucose release by 8.2 +/- 2.8 mumol g-1 20 min-1, without alteration of lactate balance. The PDI enhanced the glycogenolytic effects of nerve stimulation and of phenylephrine, accompanied by a reduction in lactate production. 6. Enoximone significantly enhanced the bile acid independent bile flow after glucagon, nerves stimulation and after administration of phenylephrine. Bile acid secretion was unaffected by the PDI. The vasoconstrictor effect of nerve stimulation was reduced by the PDI. 7. We conclude that endotoxin treatment reduces the ability of the PDI, enoximone, to increase cyclic AMP release in the perfused liver. The significant increase in cyclic AMP release after stimulation with glucagon and enoximone favours the view that RPDE3 is involved in the degradation of cyclic AMP in the liver after exposure to endotoxin. Additionally, the inhibition of the RPDE3 results in glucose release, vasodilatation and choleresis in endotoxin pretreated livers.

Animals↗
PubMed1996

HLA class II gene frequencies in Crohn's disease: a population based analysis in Germany.

BACKGROUND: Ulcerative colitis is the only known inflammatory bowel disease associated with particular HLA alleles. Whereas the association with the HLA-DRB1*15 allele has been described in several independent studies for ulcerative colitis, no contribution of HLA alleles to susceptibility in Crohn's disease has yet been shown. AIM: This study was designed to study the strength of association of HLA class II alleles as risk markers for Crohn's disease in a homogenous population in Germany. PATIENTS: A total of 4251 randomly selected control subjects, and 162 unrelated subjects with Crohn's disease were studied. Subjects were studied for their HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles. METHOD: HLA DNA typing was performed after locus specific amplification with the polymerase chain reaction and reverse dot blot hybridisation. RESULTS: The HLA-DRB1*07 was the only HLA class II allele found to be significantly associated with Crohn's disease (relative risk (RR) = 1.9, 95% CI: 1.66 to 2.14; p = 0.0001). This association remained significant after correction for the number of DRB1 alleles compared. In patients with disease onset before 35 years the RR for the disease in HLA-DRB1*07 positive subjects was found to be higher (RR = 3.1, 95% CI: 2.44 to 3.76). The HLA-DRB1*03 was significantly decreased in frequency in Crohn's disease (RR = 0.5, 95% CI: 0.39 to 0.61; p = 0.0028). CONCLUSION: The HLA-DRB1*07 allele provides risk for the disease especially in patients with younger ages of onset. These data also provide indirect evidence for an immunogenetically based heterogeneity of the disease.

Adolescent↗
PubMed1996

M1 muscarinic mechanisms regulate intestinal-phase gallbladder physiology in humans.

The contribution of muscarinic receptor subtypes to biliary control mechanisms is unclear. We investigated stimulated gallbladder function and release of associated hormones during M1-receptor blockade. Following a double-blind, randomized, crossover protocol, healthy volunteers each received placebo and telenzepine, a selective M1-receptor antagonist, as 2-h background infusion. Gallbladder contraction (by ultrasonography), bilirubin output, and release of cholecystokinin (CCK) and pancreatic polypeptide (PP) were assessed during increasing doses of endogenous (intraduodenal nutrient) and exogenous (hormonal) stimulation. All parameters were stimulated in a dose-dependent manner on placebo days. Contractile and secretory responses to low-dose caerulein (CCK analogue) were inhibited by 60-80% under telezepine, whereas high-dose (supraphysiological) stimulation overrode this effect. Similar inhibition was achieved during nutrient stimulation. CCK plasma levels rose during endogenous and exogenous stimulation but were unaffected by M1 blockade, whereas stimulated PP release was completely inhibited (> 100% decrease), reflecting suppressed vagal tone. Selective M1-receptor blockade inhibits the physiological response of the gallbladder in humans; this effect cannot be attributed to suppressed CCK release. Our findings support the hypothesis that CCK acts at the gallbladder via cholinergic nerves under physiological conditions. Viewed with our previous observations, nonselective antagonism of biliary function by atropine is primarily mediated through M1 muscarinic pathways.

Adult↗
PubMed1996

The effects of dexfenfluramine on weight loss and cardiovascular risk factors in female patients with upper and lower body obesity.

BACKGROUND: Obesity has been identified as a risk factor for atherosclerosis, and fat distribution has proved to be a critical variable. Weight loss improves health, but failure rates in dietary treatment are high. The effects of dexfenfluramine, which is useful in many patients, were studied on cardiovascular risk factors in obese female patients with upper and lower body obesity. METHODS: In a placebo-controlled, double-blind trial, which was part of a multicentre study, 52 obese female patients (body mass index 35.1 +/- 7.8 kg/m2, age 43.3 +/- 6.4 years) were given either 15 mg dexfenfluramine twice daily, or placebo in addition to a calorie-restricted diet (1500 kcal/day) for 12 months. Forty-two patients (20 with upper body obesity, 12 dexfenfluramine and 10 placebo; 22 with lower body obesity, 16 dexfenfluramine and six placebo) completed the 14-month study. RESULTS: Patients with upper body obesity lost 14.2 +/- 2.20 kg with dexfenfluramine, and 4.92 +/- 2.99 kg with placebo (P < or = 0.05). In contrast, patients with lower body obesity lost 11.1 +/- 2.89 kg with dexfenfluramine and 2.6 +/- 2.32 kg with placebo (P < 0.05). With dexfenfluramine, patients with upper body obesity lost more weight than patients with lower body obesity (P < 0.05). After 1 year of dexfenfluramine treatment, reduction of systolic blood pressure in patients with upper body obesity (157 +/- 10 versus 133 +/- 8 mmHg, P < 0.05) was significantly (P < 0.05) greater than in patients with lower body obesity (136 +/- 14 versus 127 +/- 12 mmHg). During dexfenfluramine treatment cardiovascular risk factors improved. In upper body obesity blood glucose (5.18 +/- 0.28 versus 4.40 +/- 0.34 mmol/l, P < 0.05), serum insulin (23.4 +/- 8.9 versus 13.2 +/- 4.2 microU/ml, P < 0.05) and triglycerides (1.96 +/- 0.45 versus 1.23 +/- 0.54 mmol/l, P < 0.05) decreased, and high-density lipoprotein cholesterol increased (1.0 +/- 0.14 versus 1.21 +/- 0.14 mmol/l P < 0.05). In lower-body obesity, cardiovascular risk factors were in the normal range and did not change significantly during the study. CONCLUSIONS: Dexfenfluramine lowers body weight in obese patients with upper and lower body obesity and reduces the cardiovascular risk factors clustering in upper body obesity.

Adult↗
PubMed1996

The effect of withdrawal and re-introduction of dexfenfluramine in the treatment of obesity.

In this study 25 patients, who had completed the INDEX trial (Guy-Grand et al. Lancet 1989; 2: 1142-1145) were reexamined 2 months after withdrawal of the study medication. The patients then in an open trial received dexfenfluramine (dF) for 6 months. The observed weight gain after withdrawal of study medication was higher in patients treated beforehand with dF (2.6 +/- 1.2 kg) than in patients who had received placebo (0.8 +/- 1.0 kg). In the open dF trial rate of weight loss was lower than it had initially been in the patients receiving dF from the outset of the INDEX trial (13.1 +/- 4.6 kg within 6 months). In the previous dF treated patients weight loss after re-introduction of dF was 3.7 +/- 2.7 kg. The previous placebo-treated patients, now receiving dF for the first time, lost 4.8 +/- 1.1 kg. Thus, after withdrawal of dF, patients experience weight gain, but after re-introduction of dF, renewed weight loss is achieved. However, the rate of weight loss declines with time.

Adult↗
PubMed1996

[Acute pancreatitis: diagnosis].

In the differential diagnosis of abdominal pain, acute pancreatitis may be diagnosed by its clinical features together with blood determinations and ultrasonographic findings. The primary diagnostic steps include the differentiation between biliary or non-biliary etiology of the disease. In biliary acute pancreatitis, ERCP with endoscopic sphincterotomy is recommended, although the benefit of this procedure has only been shown in patients with severe clinical courses. An early discrimination between edematous-interstitial pancreatitis [mild clinical course] and necrotizing pancreatitis [severe clinical course associated with local and systemic complications] is possible by daily CRP-monitoring. In necrotizing pancreatitis, contrast-enhanced computed tomography is the next diagnostic step, and the patient should be transferred to an intensive care unit. To differentiate between severe sterile pancreatitis and infected pancreatic necrosis, ultrasonographic or CT-guided fine needle aspiration of the pancreatic inflammatory mass is suggested. Infected pancreatic necroses are associated with systemic septic complications, which are the main mortality factor and the major reason for operative treatment of necrotizing pancreatitis.

Acute Disease↗
PubMed1996

Intrahepatic high-grade malignant non-Hodgkin lymphoma in a patient with chronic hepatitis C infection.

A 61-year-old white female with chronic hepatitis C virus (HCV) infection first diagnosed in 1994 was admitted with two newly discovered lesions in the liver suspected to represent hepatocellular carcinoma. The alpha-1-fetoprotein (AFP) level was within normal limits and there was neither clinical nor sonographic evidence of liver cirrhosis. Fine needle aspiration, however, showed an high-grade malignant centroblastic non-Hodgkin lymphoma (NHL). Staging failed to confirm extrahepatic involvement. Both a cryoglobulinemia and HIV infection were ruled out. Although the coincidence of HCV infection and NHL is not well recognized, recent studies have indicated an increased incidence of NHL and hepatitis C in up to 38% of patients with cryoglobulinemia. In these patients, the diagnosis is always one of a low-grade lymphoma. Based on its lymphoproliferative characteristics, an etiologic role for HCV in the development of NHL has been discussed, though the exact pathogenesis remains unclear.

Biopsy↗
PubMed1996

Characterization of a non-invasive, vascular model of acute necrotizing pancreatitis.

One of the vasoactive peptides that has been implicated in the progression from edematous to necrotizing pancreatitis is bradykinin. We have investigated the effect of bradykinin administration and bradykinin inhibition on an edematous model of acute pancreatitis in rats (10 micrograms/kg/h of caerulein i.v.). Within six hours i.v. bradykinin reduced circulating serum amylase levels significantly but neither affected tissue edema nor morphology. A bradykinin antagonist (HOE-140), on the other hand, reduced pancreatic edema by 70% and converted edematous pancreatitis into a hemorrhagic and necrotizing variety of the disease. In further experiments we determined the time course and the minimal dosage required for the induction of this severe and non-invasive disease variety. A single dose of caerulein (40 micrograms/kg i.p.) together with a single administration of the bradykinin antagonist HOE-140 (100 micrograms/kg s.c.) consistently resulted in hemorrhagic necrosis of the pancreas within six hours. We conclude that this simple protocol allows for the non-invasive induction of a vascular model of necrotizing pancreatitis and appears ideally suited to study the development of this severe form of the disease.

Acute Disease↗
PubMed1996

Prevalence of Helicobacter pylori infection and dyspepsia in young adults in Germany.

Data on the seroprevalence and time of acquisition of Helicobacter pylori (HP) infection in Germany are scarce. We studied the seroprevalence of HP infection and the relationship with gastrointestinal (Gl) symptoms in a group of 168 German medical students in the final year of their practical training and in 260 age-matched blood donors at the University of Ulm. Eight upper Gl symptoms were scored in a questionnaire, and blood samples were taken for the detection of HP lgG antibodies with an Enzyme Immunoassay (Bio-Rad). Values greater than 12.5 U/ml (positive) were detected in 50 medical students (28.8%) and in 96 blood donors (36.9%). At least one occasional Gl symptom was present in 71.4% of medical students and 70.7% of blood donors. When related to the HP status, 27.0% of HP negative and 32.9% of HP positive individuals were completely free of symptoms. Moderate to severe dyspeptic symptoms were reported by 17.4% of HP negative and 14.4% of HP positive individuals. We conclude that the seroprevalence of HP infection in young German adults is presently about 1/3 but that HP infection is not linked to gastrointestinal symptoms in this age class.

Adult↗
PubMed1995

The role of nitric oxide in hemodynamic and metabolic alterations induced by prostaglandin F2 alpha in the perfused rat liver.

In the liver prostaglandins have been shown to be potent regulators of portal blood flow, carbohydrate metabolism and bile secretion. It is not known whether these effects represent a direct action of prostaglandins, and it has been suggested that nitric oxide (NO) might be a critical mediator for prostaglandin induced hepatic events. We have studied whether nitric oxide formation or inhibition alters the action of prostaglandin F2 alpha (PG F2 alpha) in a single-pass liver perfusion model. The liver of untreated rats (constitutive NO-synthase) or after pretreatment with endotoxin (inducible form of NO-synthase) was perfused at a constant pressure via the portal vein. Effluate were collected in 1-min intervals and bile in 5-min intervals. In both groups the addition of PG F2 alpha (10 microM) to the perfusate for 5 min resulted in a significant increase of glucose and lactate production, and in a significant decrease in portal blood flow (-0.56 +/- 0.04 ml/g per min), in bile flow (-60.7%) and in bile acid release (-60.6%). Inhibition of NO synthase by adding NG-monomethyl-L-arginine (L-NMMA, 100 microM) to the perfusate did not affect any of the alterations induced by PG F2 alpha. Substitution of the endogenous substrate for the NO synthase L-arginine (500 microM) in the perfusate completely prevented the hemodynamic alterations induced by PG F2 alpha in endotoxin pretreated livers and limited the flow reduction (0.15 +/- 0.04 ml/g per min) in the untreated group. The substitution of L-arginine in the perfusate of endotoxin pretreated livers raised nitrite (from 1.5 +/- 0.3 to 3.6 +/- 0.7 nmol/g per min) and urea release (from 65 +/- 25 to 294 +/- 68 nmol/g per min), but had no effect on any of the other metabolic parameters and bile secretion. We conclude that PG F2 alpha increases glucose and lactate production in the perfused rat liver and decreases portal flow bile secretion. The metabolic effects induced by PG F2 alpha appear to be independent of NO mediation and hemodynamic alterations. Portal flow alone can be influenced by endogenous NO formation.

Animals↗
PubMed1995

Substance P gene expression in acute experimental colitis.

We have previously shown (Gastroenterology, 101 (1991) 1211-1219), that substance P (SP) decreases early in the colon muscle layer after induction of colitis in rabbits. Since the SP content in the colonic muscle layer was unchanged by sensory denervation with capsaicin, we assume that SP is located predominantly in intrinsic neurons of the colon, and that the decrease of SP during inflammation reflects changes in intrinsic SP content. However, damage of SP neurons by inflammation would be another likely explanation for the decrease in SP content. The aim of this study was to determine SP gene expression in intrinsic (colonic muscle layer) and extrinsic (dorsal root ganglia, DRG) neurons to prove that SP transcription is preserved during colitis as an indicator of neuronal integrity. Colitis was induced in adult white New Zealand rabbits by formalin enemas (4 ml of 0.4% formalin) followed by 0.85 ml immune complex i.v. 2 h later. The animals were sacrificed 48 h after induction of colitis, and SP content and gene expression were determined by radioimmunoassay (RIA) and Northern blot analysis, respectively. Immunoreactive SP was reduced by 40% in the colon muscle layer and by 60% in the dorsal root ganglia (L4-S4) in the animals with colitis compared to controls without colitis. In contrast to the protein data, SP gene expression was not significantly altered in the colon muscle layer and the dorsal root ganglia 48 h after induction of inflammation compared to the control tissue. The preserved SP gene expression suggests that the intrinsic and extrinsic SP neurons are viable in this inflammatory model. The decreases of immunoreactive SP in the colonic extracts and the DRG after induction of colitis suggest that SP is released from extrinsic and intrinsic neurons during inflammation.

Acute Disease↗
PubMed1995

Expression and in-situ localization of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in pancreatic cancer.

Pancreatic cancer shows a strong desmoplastic reaction characterized by a remarkable proliferation of interstitial connective tissue (collagens type I and III, fibronectin). In this study we have analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix-degrading metalloproteinases (MMP-1, -2, -3 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in pancreatic cancer and control pancreatic tissue by Northern-blot analysis and mRNA in situ hybridization. Transcripts for MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) were not detectable in pancreatic cancer and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72-kDa collagenase IV), MMP-9 (92-kDa collagenase type IV), TIMP-1 and TIMP-2 were elevated in the majority of pancreatic-cancer tissue samples as compared to control pancreatic tissue. A good correlation was seen between overexpression of these MMPs and TIMPs and the steady-state levels of transcripts coding for extracellular matrix proteins, the amount of collagen protein and the severity of the desmoplastic reaction. In situ hybridization studies localized transcripts coding for collagens type I and III to spindle-shaped stromal cells, whereas transcripts for MMP-2, MMP-9, TIMP-1 and TIMP-2 were found in both stromal and tumor cells. However, MMP-2 transcripts appeared to be more abundant in stromal cells, TIMP-1 and TIMP-2 transcripts were evenly distributed over tumor and stromal cells and relatively more MMP-9 transcripts were found in tumor cells. We conclude that, in human pancreatic cancer, MMP-2, MMP-9, TIMP-1 and TIMP-2 may be involved in processes leading to the strong desmoplastic reaction observed in these tumors. Both stromal and tumor cells appear to be the source of MMPs and TIMPs in human pancreatic cancer.

Blotting, Northern↗