PubMed Health⌕ Search

Biomedical subjects

Niels Teich

Publications and source records attributed to Niels Teich.

33 records · Page 2Linked to original sources
PubMed2004

Chronic parotitis: not another SPINKosis.

INTRODUCTION: Pancreatitis and parotitis share several etiological, pathohistological and functional similarities. It arose from recent pancreatitis research that some cases of chronic pancreatitis are associated with mutations of the serine protease inhibitor, Kazal type-1 (SPINK1). We tested the hypothesis that the pancreatitis-associated N34S mutation of SPINK1 is also a risk factor for chronic parotitis. METHODS: Reverse-transcriptase polymerase chain reaction was used to investigate SPINK1 transcription in the parotid gland. Forty-five blocks of formalin-fixed, paraffin wax-embedded tissues with chronic parotitis of unknown cause were analyzed for the SPINK1-N34S mutation. RESULTS: The SPINK1 gene is transcribed in the parotid gland. Two of the 45 patients (4.4%) with chronic parotitis carried the N34S mutation heterozygously. Of 82 healthy blood donors, 3 subjects (3.7%) were identified as carrying this mutation heterozygously (p = 0.83). CONCLUSION: The SPINK1-N34S mutation is not associated with chronic parotitis.

Carrier Proteins↗
PubMed2004

Genetic aspects of chronic pancreatitis.

The classical feature of hereditary pancreatitis (HP) is characterized by recurrent episodes of acute pancreatitis or a priori chronic pancreatitis in several members of one family. In 1996, the identification of the first HP-associated mutation in the cationic trypsinogen gene provided a breakthrough in our understanding of the pathogenesis of chronic pancreatitis. In the following years, several different mutations in the same gene have been found in a large number of investigated families. Most intriguing, HP patients have a more than 50-fold increased risk of pancreatic ductal cancer in comparison with expected pancreatic cancers in the general population. Variants of the major intrapancreatic trypsin antagonist SPINK1 have implications for more common forms of chronic pancreatitis. Research has focussed on the SPINK1-N34S-mutation, which is closely associated with tropical, alcoholic, or "idiopathic" chronic pancreatitis. Chronic pancreatitis represents a variable part of the cystic fibrosis syndrome, which is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Several groups have reported an increased prevalence of CFTR mutations in patients with chronic pancreatitis of different etiology. In this review, we summarize interesting clinical and biochemical features of genetic variants in these genes which are associated with chronic pancreatitis.

Carrier Proteins↗
PubMed2003

Evaluation of Pankrin, a new serum test for diagnosis of acute pancreatitis.

AIM: Evaluation of a new serum test for diagnosis of acute pancreatitis. PATIENTS AND METHODS: One hundred and sixty-three patients presenting with acute abdominal pain were included into the study. Acute pancreatitis was diagnosed by CT or ultrasound. Serum samples were taken 0-1 days, 2-3 days, and 4-5 days after onset of symptoms and C-reactive protein, lipase, elastase, and amylase were determined. As a further parameter, Pankrin, a newly available kit for the measurement of a mixture of elastase and other pancreatic secretory proteins was used. As control, serum from 558 apparently healthy blood donors was analysed. The receiver operator characteristics (ROC) and the areas under the curves (AUC) were calculated for each individual test. RESULTS: In Western blot analysis the antibodies of the Pankrin assay detected the majority of protein bands in human pancreatic juice. In blood donors, the median value of Pankrin was 88 U/ml (range 14-316 U/ml). In 16 from 163 patients with acute abdominal pain, acute pancreatitis was diagnosed and the median Pankrin level in samples collected on days 0-1 was 345 U/ml (range 220-518 U/ml, p<0.0001). In those patients with abdominal pain but without pancreatitis, the median was 116 U/ml (range 17-396 U/ml). The ROC-curves for amylase, lipase, elastase, and Pankrin from samples collected after 0-1 days were similar (area under the curves (AUC) >0.98). After 2-3 days, the AUC of all markers decreased (AUC 0.80-0.89) and after 4-5 days the AUC of Pankrin (0.85) was higher than all other parameters. CONCLUSION: In those patients with abdominal pain, who present several days after onset of pain, the new serum test for pancreatitis, Pankrin, could be of help to improve the diagnosis of pancreatitis.

Abdomen, Acute↗
PubMed2003

UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer.

BACKGROUND & AIMS: Chronic pancreatitis and pancreatic adenocarcinoma are associated with alcohol abuse, consumption of tobacco smoke, and environmental aromatic hydrocarbon exposure. The role of genetic factors is incompletely defined. Uridine 5'-diphosphate glucuronosyltransferases are phase II detoxifying enzymes capable of tobacco-borne toxicant inactivation and cellular protection. This study analyzes UGT1A7 gene polymorphisms in pancreatic diseases. METHODS: Genomic DNA from northern German white patients with pancreatic adenocarcinoma (n = 52) and chronic pancreatitis (n = 146), as well as healthy blood donors (n = 235) was analyzed by UGT1A7-specific PCR, sequencing analysis, and temperature gradient gel electrophoresis. Pancreatic expression of UGT1A genes was identified by duplex reverse-transcription PCR. RESULTS: Predominant expression of the UGT1A7 gene was identified in human pancreatic tissue. Pancreatic adenocarcinoma was associated with the low detoxification activity UGT1A7*3 allele, which combines the W208R, N129K, and R131K mutations (odds ratio [OR], 1.98; 95% confidence interval [CI ], 1.24-3.14; P = 0.003). The association of UGT1A7*3 was especially strong in smokers with pancreatic carcinoma who were younger than 55 years (OR, 4.7; 95% CI, 1.9-11.8; P = 0.0009). Chronic pancreatitis was also associated with UGT1A7*3 (OR, 1.76; 95% CI, 1.26-2.46; P = 0.0009). UGT1A7*3 was specifically associated with the subgroup of patients with alcoholic pancreatitis, of whom 89% were smokers (OR, 2.24; 95% CI, 1.46-3.43; P = 0.0001) but was not associated with the nonalcoholic pancreatitis subgroup. CONCLUSIONS: The UGT1A7 gene is predominantly expressed in human pancreas. The low detoxification activity UGT1A7*3 allele is identified as a novel risk factor of pancreatic diseases defining the interaction of genetic predisposition and environmentally induced oxidative injury.

Adenocarcinoma↗
PubMed2003

Analysis of tumour necrosis factor alpha and interleukin 10 promotor variants in patients with chronic pancreatitis.

OBJECTIVE: Cationic trypsinogen gene mutations are strong risk factors of hereditary pancreatitis. However, 20% of subjects with a trypsinogen mutation never get pancreatitis and the cause of this incomplete penetrance is unknown. We investigated the influence of interleukin 10 (IL10) and tumour necrosis factor alpha (TNFalpha) promotor variants on the manifestation of chronic pancreatitis of different underlying causes and in pancreatic cancer. METHODS: A total of 335 German patients with chronic pancreatitis were investigated. In 157 patients the disease was related to alcohol abuse; the other cases were of non-alcoholic origin. In the latter group, the serine protease inhibitor, Kazal type 1 (SPINK1) mutation N34S was found in 72 patients and the trypsinogen mutations N29I or R122H were present in 60 patients; in the remaining 46 patients no mutation was found. In addition, we studied 208 patients with pancreatic cancer. As controls, 116 healthy blood donors and 25 healthy carriers of the trypsinogen mutations N29I or R122H were investigated. After DNA extraction from blood leucocytes, genotyping for the cytokine polymorphisms was performed by induced heteroduplex generators and/or direct DNA sequencing of the IL10 and TNFalpha promotor regions. RESULTS: The frequencies of the promotor polymorphisms of IL10-627A, IL10-1117A, TNF-238A and TNF-308A in patients with alcoholic chronic pancreatitis, idiopathic pancreatitis, SPINK1-N34S-associated chronic pancreatitis and pancreatic cancer did not differ significantly from the control group. The variant TNF-238A was two to four times more frequent in index patients with trypsinogen mutations than in all other groups. The analysis of the allelic frequencies of whole families with trypsinogen mutations revealed that all subjects with the TNF-238A variant suffered from chronic pancreatitis, whereas all intrafamilial controls with wild-type TNF were unaffected. CONCLUSIONS: TNFalpha and IL10 promotor variants are not associated with a manifestation of chronic pancreatitis or pancreatic cancer. The variant TNF-238A, however, might be a relevant risk factor for disease manifestation in families with hereditary pancreatitis.

Case-Control Studies↗
PubMed2003

N34S, a pancreatitis associated SPINK1 mutation, is not associated with sporadic pancreatic cancer.

BACKGROUND: The SPINK1 mutation N34S is associated to chronic pancreatitis of idiopathic, alcoholic and tropic origin. Our aim was to evaluate its prevalence in patients with sporadic pancreatic cancer. METHODS: The N34S allele of SPINK1 was analyzed by melting curve analysis using fluorescence resonance energy transfer (FRET) probes and the LightCycler in 159 German patients with sporadic pancreatic cancer (83 male, 76 female, median age of diagnosis 61 years, range 36-84 years) and 492 healthy controls. RESULTS: The N34S mutation was detected in 2 (1.3%) of the 159 patients with pancreatic cancer and in 8 (1.6%) of the 492 controls (not significant). CONCLUSION: The N34S mutation of SPINK1 appears not to be a distinct genetic risk factor in patients with sporadic pancreatic cancer.

Adult↗
PubMed2003

The course of genetically determined chronic pancreatitis.

CONTEXT: The clinical course of chronic pancreatitis in patients with mutations of cationic trypsinogen and the trypsin inhibitor SPINK1 has not yet been characterized. SETTING: Cationic trypsinogen (PRSS1) and the serine protease inhibitor, Kazal type 1 (SPINK1), were analyzed in patients with pancreatitis of unclear origin. PATIENTS: Eighty subjects with trypsinogen mutations (21x N29I, 59x R122H) and 59 patients with the SPINK1 N34S variant (11 homozygous, 48 heterozygous) were included in the study. MAIN OUTCOME MEASURES: In patients with mutations of PRSS1 (N29I, R122H) and SPINK1 (N34S) the parameters such as calcification, dilatation of the main pancreatic duct, diabetes mellitus, hospital treatments, and surgery were recorded. DESIGN: Case control studies were performed to compare both mutational groups, and the follow-up time served as a matching criterion. The Kaplan-Meier analysis was used to estimate the time course of the symptoms. RESULTS: Ten years after the onset of the disease, the probability (+/-SE) of symptoms in patients with PRSS1 mutations was as follows: 1st hospital stay: 86+/-4%; calcification: 21+/-4%; duct dilatation: 26+/-9%; surgery: 19+/-5%; diabetes: 6+/-5%. After 25 years, we found the following data: 1st hospital stay: 96+/-3%; calcification: 38+/-8%; duct dilatation: 38+/-8%; surgery: 37+/-10%; diabetes: 28+/-8%. A case-control-study of 38 pairs of patients with either PRSS1 or SPINK1 mutations showed that the probability of duct dilatation, diabetes and calcification was slightly higher in patients having a SPINK1 mutation. There was no difference between those subjects with a homozygous or heterozygous SPINK1 mutation. In comparison to alcoholic chronic pancreatitis patients, the PRSS1 associated disease revealed a lower frequency of calcification and diabetes. CONCLUSIONS: The progression of chronic pancreatitis was slightly more rapid in patients with SPINK1 mutations than in patients with cationic trypsinogen mutations, but was much less than in those having alcoholic chronic pancreatitis.

Case-Control Studies↗
PubMed2003

Clinical value of a new fecal elastase test for detection of chronic pancreatitis.

INTRODUCTION: Several pancreatic function tests exist, but their role in the diagnosis of chronic pancreatitis is controversial. Here we analyzed the clinical value of a newly available fecal elastase assay. MATERIALS AND METHODS: Fecal samples from 212 patients treated in our hospital from January to September 2002 were taken. Chronic pancreatitis was assumed when ductal alterations were present in ERCP. The severity of disease was assessed according to the Cambridge classification. Elastase (test from ScheBo, Germany) and chymotrypsin (Roche Diagnostics) were measured. As a new parameter an elastase ELISA from BIOSERV (Rostock, Germany) was employed. Specificity, sensitivity, and accuracy of each test as well as the ROC curves were calculated. RESULTS: In 45 patients (21.2%) chronic pancreatitis was diagnosed. The sensitivities of elastase from ScheBo, elastase from BIOSERV and chymotrypsin were 68.9%, 77.8%, and 57.8%, respectively. The corresponding specificities were 77.2%, 76.0%, and 52.7%. When a cut-off for the elastase tests of 100 U/ml was used the sensitivities (57.8%) and the specificities (89.2%) for both elastase tests were similar. The areas under the ROC curves for the ScheBo elastase, BIOSERV elastase, and chymotrypsin were 0.805, 0.840, and 0.628, respectively. The higher AUC of the BIOSERV test was maintained when patients with mild-moderate chronic pancreatitis (Cambridge I-II) were analyzed separately. CONCLUSION: The new elastase assay could probably replace the older test and was also much better than chymotrypsin.

Area Under Curve↗
PubMed2002

Cathepsin B cleavage of the trypsinogen activation peptide.

BACKGROUND: Cathepsin B is thought to play a central role in intrapancreatic trypsinogen activation and the onset of pancreatitis. A recent investigation of the cathepsin B mediated activability of wildtype trypsinogen and their mutations N29I, N29T and R122H, which are associated to hereditary pancreatitis, revealed no differences. This action seems to be restricted to the K23-I24 peptide bond, which is the trypsinogen activation bond. Here we investigated the influence of the mutations D22G and K23R of the trypsinogen activation peptide on the cleavability by cathepsin B. METHODS: To investigate the functional impact of the TAP mutations on cathepsin B mediated cleavage of the trypsinogen activating K23-I24 bond, the corresponding peptides pWT, APFDDDDKIVGG; pD22G, APFDDDGKIVGG; and pK23R, APFDDDDRIVGG were digested with cathepsin B for 30 min at pH 3.8 and 5.0, and the fragments were analysed by high-performance liquid chromatography. RESULTS: Without cathepsin B, less than 1 % of the peptides were hydrolysed. After a 30-minute digestion with cathepsin B at pH 5, 96% of pWT, 48% of pK23R, but only 2.4% of pD22G were hydrolysed. At pH 3.8, the cathepsin B cleavage of pWT and pK23R was less than at pH 5, whereas the cleavage of pD22G was completely inhibited. CONCLUSIONS: Cathepsin B mediated trypsinogen activation seems not to be a crucial pathogenic step in hereditary pancreatitis patients with the trypsinogen mutations D22G and K23R.

Cathepsin B↗
PubMed2002

Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants.

OBJECTIVES: Mutations of the cationic trypsinogen (CT) and the serine protease inhibitor, Kazal type 1 (SPINK 1) are associated with chronic pancreatitis. After mutational screening of a cohort of patients with nonalcoholic chronic pancreatitis, we report three novel variants of the trypsinogen molecule and the clinical characteristics of the carriers. METHODS: The coding region of the exon 2 and 3 of the CT gene of 523 patients with chronic nonalcoholic pancreatitis (108 patients with suspected hereditary pancreatitis (HP) and 415 patients with "idio pathic" pancreatitis [IP]) and 82 controls was analyzed after polymerase chain reaction amplification. Clinical characteristics were obtained by questioning the patients and their relatives and physicians. HP was suspected when two members of a family had chronic pancreatitis. A restriction digestion was used to analyze the N34S mutation SPINK1. RESULTS: The mutation R122H of the cationic trypsinogen was found in 21 index patients, N291 in six index patients, and A16V and D22G in one index patient, all from HP families. The N34S mutation of SPINK1 was found in two index patients with a family history of HP. In three patients, the novel point mutations L104P, R116C, and C139F of the cationic trypsinogen were found. A clear autosomally dominant inheritance of chronic pancreatitis was not present in these families. In 75 index patients from HP families (69.4%), no mutation could be found. The SPINK 1-mutation N34S was detected in only one patient carrying a CT mutation, and was found in 68 (16.4%) of patients with IP. CONCLUSIONS: The R122H and N291 mutations of CT are the most common disease-associated mutations in HP; the N34S mutation of SPINK I is the most frequent genetic risk factor associated with IP. The CT gene carries several variations that could be associated with chronic pancreatitis. To avoid overestimating the pathogenetic impact of novel trypsinogen variants, a detailed clinical characterization of all patients with early onset chronic pancreatitis is mandatory.

Adult↗