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Biomedical subjects

M Löhr

Publications and source records attributed to M Löhr.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cancer of the pancreas: from concordant classification to standardized treatment. International Symposium at Kloster Irsee, Germany, 2-5 October 1996.

There has been a slow but steady improvement in the results of treatment for exocrine pancreatic cancer in the last decade. One obstacle to further improvement has been lack of standardization for reporting of results, from classification to surgery and follow-up. This four-day symposium was organized in order to bridge the clinical praxis of curatively intended radical pancreatic surgery to scientific evaluation of its results. The meeting comprised four workshops, three special lectures, and seven plenary sessions.

Humans↗
PubMed1997

[Interventional endoscopic therapy of chronic pancreatitis].

BACKGROUND AND AIM: Complications in chronic pancreatitis, such as duct occlusion due to stenosis or stones can be treated by interventional endoscopic procedures. The benefit of such procedures and the effect on the clinical course is still under debate. Therefore, it was the aim of this study to analyze the effect of endoscopic interventional procedures in more detail with respect to technical and clinical benefit. PATIENTS AND METHODS: 100 patients with chronic pancreatitis (cP) were studied retrospectively. In 58 patients an indication for interventional endoscopic therapy was given (45 +/- 12 yrs; 46 M, 12 F; cP 1 degree: n = 1, cP II degree: n = 8, cP III degree: n = 49). The patients were allocated to three groups: stenosis (n = 18), pancreatic duct stones (n = 18) and stenosis and pancreatic duct stones (n = 20). In two patients no visualization of the main pancreatic duct was performed due to cholestasis that was treated primarily. In total, 295 endoscopic procedures were performed (EPT, duct dilatation, plastic endoprothesis, ESWL, mechanical lithotripsy). Technical success was 95%. All stenoses could be dilated or bridged by plastic stents. Fragmentation of main pancreatic duct stones was achieved in 92%. The overall complication rate of all 319 endoscopies (fever, bleeding, stent dislocation) was 15.8%. Five patients had to undergo surgery, however, not as a direct consequence of complications from or unability of endoscopic procedures. 86% of the patients reported complete pain relief after the endoscopic-interventional procedures and 62% during the follow-up interval (7.4 +/- 6.3 months). 59% of the patients with weight loss and 58% of the patients with initially stable weight experienced a weight gain following endoscopic-interventional therapy. Individual patients showed improvement of endocrine or exocrine pancreatic function. 82% of the patients did not require inhouse treatment or emergency admission to the hospital whereas three admissions on average were recorded prior to endoscopic interventional treatment. Therefore, we conclude that a subset of patients does benefit from endoscopic interventional therapy of complications of chronic pancreatitis. However, a controlled prospective study is still mandatory.

Adolescent↗
PubMed1997

Pancreatitis in systemic scleroderma.

We report the case of a 61-year-old woman, who suffered from abdominal pain, nausea, vomiting and fever. She had a past medical history of acute rheumatism, pyelonephritis and systemic scleroderma. Since 1971 she was hospitalized many times because of recurrent abdominal pain with increased serum amylase and lipase values. On admission, she was in distress and demonstrated clinical signs of acute pancreatitis. The link between systemic lupus erythematosus and acute pancreatitis is discussed in view of the reported cases of the world literature.

Acute Disease↗
PubMed1996

Expression and function of receptors for extracellular matrix proteins in human ductal adenocarcinomas of the pancreas.

Extracellular matrix proteins (ECM) may influence cellular differentiation via their receptors, the integrins. We recently presented evidence that ductal adenocarcinomas of the pancreas are able to produce ECM in vitro and in vivo (Br J Cancer 1994;49:144-51). This study examines whether pancreatic carcinoma cells are able to interact with ECM by expressing functionally active integrins. In eight human pancreatic tumor cell lines (AsPC-1, BxPC-3, CAPAN-1 and -2, PANC, PaTu-2, -3, and -44) and six xenografted tumors RNA and protein expression of integrin subunits alpha 5 (fibronectin receptor), alpha 6 (laminin receptor), and alpha V (vitronectin receptor) was investigated. In addition, alpha 1-alpha 6 and alpha V as well as beta 1-beta 4 were studied by fluorescence-activated cell sorter analysis. Integrin function was tested by attachment assays. alpha 2, alpha 3, alpha 5, alpha 6, and alpha V as well as beta 1, beta 3, and beta 4 were expressed, at both the RNA and the protein level, by all pancreatic tumors in vitro and in vivo. The tumor cell lines showed dose dependent adhesion to collagen, fibronectin, and laminin. Integrin expression could be modulated in part by serum depletion. None of the tumors showed alpha 1, alpha 4, and beta 2. Tumor cell differentiation or production of ECM was not correlated with integrin expression. Pancreatic ductal adenocarcinomas express a certain pattern of functionally active integrins that enable interaction with most matrix proteins, e.g., collagen, fibronectin, and laminin. Pancreatic adenocarcinomas possess both the ligands and the receptors of the extracellular matrix network. We speculate that through both classes of molecules, the tumor cells may bind to fibroblasts and probably stimulate their growth. However, it remains unclear whether and how integrin-ECM interaction exerts an influence on tumor cell differentiation.

Animals↗
PubMed1995

[Restriction enzyme mismatch polymerase chain reaction in the demonstration of Ki-ras-oncogene mutation in carcinoma of the pancreas].

A pilot study was undertaken to test whether combining the polymerase chain reaction with restriction fragment length polymorphism is suitable for the routine diagnosis of carcinoma of the pancreas. The method makes it possible to recognize point mutations in codon 12 of the Ki-ras oncogene. 60 cytological specimens from the pancreatobiliary tract, the bronchopulmonary system (by bronchoalveolar lavage or from pleural effusion) and ascites were tested. Results from nine pancreas carcinoma cell lines served as control. A PCR product was successfully amplified in all cell lines and 47 of the clinical specimens. In all eight samples in which a mutated Ki-ras oncogene was demonstrated, there was at least a suspicion of malignancy by cytological examination. A mutation was also found in four of five pancreas carcinomas. But no mutation was found in one, clinically certain, case of pancreas carcinoma. The described method is an elegant and, most of all, rapid means to complement and optimize any cytological diagnosis.

Ascitic Fluid↗
PubMed1995

Extracellular matrix proteins in human bile and gallstones.

OBJECTIVE: To investigate the presence of extracellular matrix (ECM) proteins in human bile and gallstones and to determine whether they play a role in gallstone formation. METHODS: ECM components [procollagen-III-peptide (P-III-P), laminin, and hyaluronic acid] in bile from patients with (n = 22) and without (n = 6) gallstone disease were investigated by immunoassay. Bile, gallstones, and serum were assayed for extracellular matrix components in an additional 19 patients with gallstone disease and gallstones were analysed in a third set of 26 patients. The expression of hyaluronic acid synthetase in bile duct and gall bladder epithelia was investigated by immunocytochemistry. RESULTS: Hyaluronic acid levels were significantly elevated in hepatic and gall bladder bile, but not in the serum of patients with compared with those without gallstone disease (137 versus 81 micrograms/l, respectively; P < 0.05). No differences were found between hepatic and gall bladder bile. Procollagen-III-peptide and laminin were detected in the hepatic bile of patients in both groups. Laminin levels were higher in gall bladder bile than in serum in all patients and measurable amounts of hyaluronic acid were found in gallstones. The amount of hyaluronic acid was inversely correlated to the volume of the gallstone, i.e., the smallest gallstones contained the highest levels of hyaluronic acid. No procollagen-III-peptide or laminin was found in the gallstones. Immunocytochemistry of the epithelial cells of bile duct and gall bladder mucosa stained strongly for hyaluronic acid synthetase. CONCLUSIONS: Hyaluronic acid as a progenitor of ECM can be detected in bile and is significantly elevated in patients with gallstone disease. Small gallstones contain more hyaluronic acid than large stones, suggesting that hyaluronic acid may play a role in gallstone formation, particularly since it is produced by the epithelial lining of bile ducts and is found in gall bladder mucosa.

Adolescent↗
PubMed1994

Human ductal adenocarcinomas of the pancreas express extracellular matrix proteins.

Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue reaction. To test the hypothesis that stroma components are synthesised and produced by the tumour cells themselves, eight cell lines as well as six xenografted tumours from human ductal adenocarcinomas of the pancreas were examined for the expression of extracellular matrix proteins (ECM), using cDNA probes and antibodies to collagen types I, III and IV, vitronectin, fibronectin, undulin and laminin. All tumour cell lines (CAPAN-1, CAPAN-2, AsPC-1, BxPC-3, PANC-1, PaCa-2, PaCa-3, PaCa-44) and xenografted human pancreatic tumours expressed at least one of the examined ECM at the RNA (collagen type IV > laminin = fibronectin = vitronectin > collagen type III > undulin > collagen type I) or protein level (collagen type IV = collagen type III > vitronectin > laminin > collagen type I = fibronectin > undulin). In nude mouse tumours expression of laminin and collagen I was most pronounced in well-differentiated carcinomas. In a few tumours, collagen type III, vitronectin and undulin were expressed on the luminal side of the neoplastic glands, suggesting loss of normal polar differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a varying extent in all but one cell line (AsPC-1). The results suggest that human pancreatic ductal adenocarcinomas cells are capable of synthesising and producing extracellular matrix proteins in vitro and in vivo, but that the extent and pattern of ECM expression differs between the various tumours and conditions tested.

Animals↗
PubMed1994

The renal basolateral transport system for organic anions: properties of the regulation mechanism.

The aim of the present study was to investigate whether the activity of the renal basolateral transport system for organic anions is modulated by protein kinase C (PKC). The studies were performed on isolated nonperfused S2 segments of proximal tubules, microdissected from rabbit kidneys without the use of enzymatic agents. Several PKC-activating substances and staurosporine, a PKC inhibitor, were added to the incubation solution containing 3H-PAH at 6.5 x 10(-7) M as a marker substance for the basolateral anion transporter. The phorbol ester phorbol 12-myristate 13-acetate showed dose-dependent effects on the tubular PAH uptake, inducing a 2-fold increase in the PAH transport rate compared with control at a concentration of 10(-7) M. Oleyl-2-acetylglycerol, a membrane permeant analog of the physiological PKC activator diacylglycerol, had similar effects, but the maximum stimulating concentration was 10(-5) M. The shift to higher concentrations might be due to an intracellular metabolization of oleyl-2-acetylglycerol. In addition, myoinositol, a precursor of the PKC-activating pathway, induced a 2-fold increase in PAH accumulation at a concentration of 10(-5) M. These effects were abolished by the administration of staurosporine at low concentrations (10(-9) and 10(-8) M). Staurosporine on its own diminished the PAH uptake in a concentration-dependent manner at bath concentrations ranging from 10(-7) to 10(-5) M. We conclude that the PKC system may be an important modulator of the basolateral PAH transport in renal S2 proximal tubules.

Alkaloids↗
PubMed1993

Isolation, culture, and characterization of human pancreatic duct cells.

To establish a suitable control for pancreatic tumor cell lines, we have isolated and cultured primary human pancreatic duct cells from transplant donors. Duct cells were isolated by dissecting the main pancreatic duct and first-degree branches and enzymatic digestion. Aggregates of cells were cultured for 1 up to 5 weeks and monitored for changes in morphology and growth by phase contrast microscopy. Contaminating fibroblasts were mechanically removed from day 4 on and by cloning of epithelial cells. Cultured cells were characterized by phase contrast microscopy, electron microscopy, and immunofluorescence with antibodies against intermediate filaments (cytokeratins, vimentin, desmin), mucins (Du-Pan-2, CA 19-9), carbonic anhydrase II, acinar cell enzymes (amylase, lipase, trypsin), and islet cells. About 90% of the cultured cells could be identified as ductal epithelial cells by their expression of cytokeratins, mucins, and carbonic anhydrase II. These cells showed the ultrastructural features of duct cells. After 3-5 weeks of culture, most of the cultured cells showed co-expression of cytokeratins and vimentin in addition to duct cell markers. About 10% of cells were contaminating fibroblasts (vimentin positive, cytokeratin negative). The cultured normal human duct cells as the postulated cells of origin of the pancreatic adenocarcinoma may serve as a useful control for cultured pancreatic tumor cell lines.

Cell Separation↗
PubMed1992

Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.

Aged↗
PubMed1991

[Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects].

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗