Biomedical subjects

Andreas Kage

Publications and source records attributed to Andreas Kage.

8 recordsLinked to original sources

PubMed2006

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Acute Disease↗

PubMed2006

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Base Sequence↗

PubMed2006

An in vitro microbial-based model for studying caries-preventive agents.

OBJECTIVE: The aim of the study was to develop an in vitro microbial-based caries model to test potentially caries-preventive agents. MATERIAL AND METHODS: In this model, cariogenic Streptococcus mutans biofilms are grown on tooth samples within a reaction chamber hermetically surrounded by a bacteria-tight glove box allowing the manipulation of specimens during operation. The specimens were mounted in two rows on the inner and outer rims of a specimen turntable passing several inlet pipes transporting all necessary media. Using 64 lower incisors in 4 experiments, a 10 ppm NaF solution and an experimental potentially caries-preventive glycan solution were tested compared to a water control. The mean lesion depth was determined by confocal laser scanning microscopy. RESULTS: The depths of the caries-like lesions showed no statistically significant difference irrespective of whether the specimens were mounted on the inner or outer rim of the specimen turntable. As expected, the NaF solution inhibited the development of caries-like lesions almost completely. The experimental glycan solution revealed a statistically significantly lower demineralization depth compared to the control and a significantly higher depth compared to the NaF group. The system could be operated over a period of more than 9 weeks without unintentional contamination and the manipulation of the tooth specimens could be accomplished. CONCLUSIONS: In conclusion, our in vitro system is suitable for testing potential caries-preventive agents in a reproducible way by using whole tooth samples and offers full access together with the possibility of manipulating the specimens during operation.

Biofilms↗

PubMed2006

The proportion of pseudo-halitosis patients in a multidisciplinary breath malodour consultation.

AIM: To report the data from a multidisciplinary bad breath consultation in Germany. MATERIALS AND METHODS: In this cross sectional study, 407 patients attending a bad breath consultation were examined by a specially trained dentist, with an ENT-specialist, an internist, and a psychologist on call. RESULTS: All patients reported suffering from bad breath but only 72.1% showed detectable signs of breath malodour. Within this group, 92.7% revealed an oral cause, 7.3% revealed an extra-oral cause. Within the group without malodour, 76.3% had received prior diagnostics and treatments from other doctors, whereby 36% had received one or more gastroscopies and 14% had undergone an ENT operation. In only ten cases had an organoleptic evaluation of the putative malodour been performed. CONCLUSION: Our data reveal that breath malodour is mainly of oral origin and that patients with pseudo-halitosis are frequently not diagnosed correctly by doctors, resulting in a considerable amount of over-treatment.

Adolescent↗

PubMed2003

Salivary IgA in response to periodontal treatment.

There is evidence that the quantity of antigen load is crucial for the activation of IgA immune responses. In order to investigate the relevance of these findings in aggressive periodontitis, salivary antibody responses were measured during non-surgical and antibiotic treatment. Twenty-one patients with generalized aggressive periodontitis were monitored for total salivary IgA and IgA reactive to Porphyromonas gingivalis in resting and stimulated whole saliva. Non-surgical treatment included full-mouth professional tooth cleaning and subgingival scaling and root planing (SRP) under local anesthesia. Patients were recalled at 3 months and 6 months following systemic antibiotic treatment. Non-parametric statistics showed significant improvements in the clinical parameters in all patients. Between baseline and 4 wk following SRP, median concentrations of total IgA decreased both in resting (-46%) and in stimulated (-33%) saliva. The P. gingivalis-specific IgA activity showed a twofold increase at 4 wk after SRP. In addition to these changes, periodontal treatment of aggressive periodontitis did not appear to affect salivary IgA, and there were no significant correlations of IgA to the clinical parameters. In conclusion, salivary IgA responses during periodontal treatment were not found to have a diagnostic or prognostic significance.

Adolescent↗

PubMed2002

White blood cell count in generalized aggressive periodontitis after non-surgical therapy.

BACKGROUND: Periodontal bacteria are known to invade the systemic circulation. Chronic low-level bacteremia and a systemic inflammatory response have been suggested as a pathogenetic link between periodontal disease and atherosclerosis. The purpose of this study was to examine the systemic effect of a non-surgical therapy on white blood cell count (WBC count) and differential blood count in smoking and non-smoking generalized aggressive periodontitis (GAP) patients. METHODS: 27 adult periodontitis patients (13 smokers and 14 non-smokers) with previously untreated GAP were subjected to 3 sessions of oral hygiene procedure. Afterwards, the patients were treated by scaling and root planing under local anaesthesia. Periodontal examinations were performed after supragingival pretreatment and three months after subgingival therapy. Pocket probing depth (PPD) and relative attachment level (RAL) were measured with Florida probe and disc probe. Accompanying clinical evaluation venous blood samples were taken to analyse the WBC counts and differential blood counts. For statistical analysis non-parametric tests were utilized. RESULTS: No clinical or demographic differences were found between smokers (n=13) and non-smokers (n=14). PPD, bleeding on probing (BoP) and suppuration improved significantly after therapy both in smokers and non-smokers. Following periodontal treatment WBC counts, neutrophil and platelet counts decreased significantly in non-smokers (p< or =0.004), while in smokers only platelet counts were significantly reduced (p=0.006). Non-smokers showed a significantly higher reduction of WBC counts (p=0.005) and neutrophils (p=0.001) compared to smokers. CONCLUSION: The results indicate that a therapeutical intervention may have a systemic effect on the blood count in GAP patients. This effect seems to differ between smokers and non-smokers.

Adult↗

PubMed2002

Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.

BACKGROUND & AIMS: Tropical calcific pancreatitis (TCP) is a chronic pancreatitis unique to developing countries in tropical regions. The cause of TCP is obscure. Whereas environmental factors, such as protein energy malnutrition and ingestion of cassava, have been implicated, a genetic predisposition to the disease also may be important. In the present study we report on mutations in the serine protease inhibitor, Kazal type 1 (SPINK1) gene in north Indian patients with TCP. METHODS: We studied 66 unrelated TCP patients (44 men, 49 with diabetes, and 6 with family history of TCP), 25 relatives, and 92 healthy control subjects. Samples were analyzed for SPINK1 variants (-53C>T, L14P, N34S, P55S, and 272T>C) and cationic trypsinogen (PRSS1) variants (A16V, K23R, N29I, and R122H) by melting curve analysis. RESULTS: Twenty-nine patients (44%) carried the N34S missense mutation, of whom 9 (14%) were homozygotes. In contrast, only 2 (2.2%) control subjects were N34S heterozygotes (prevalence ratio 20.2; 95% confidence interval 5.0-81.8; P < 0.0001 vs. TCP). The severity of pancreatitis did not differ between TCP patients with or without N34S, or among those heterozygous or homozygous for N34S. Among TCP patients with or without diabetes, the frequency of N34S carriers (43% vs. 47%) and N34S homozygotes (14% vs. 12%) was similar. CONCLUSIONS: TCP is highly associated with the SPINK1 N34S mutation. The high prevalence of N34S in TCP patients with and without diabetes suggests that these 2 subtypes have a similar genetic predisposition. The genetic predisposition to TCP resembles, at least in part, the idiopathic chronic pancreatitis found in industrialized countries.

Adult↗

PubMed2002

Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis.

OBJECTIVE: The pathogenesis of chronic pancreatitis (CP) is poorly understood. Genetic studies revealed mutations in the cationic trypsinogen gene and an increased frequency of cystic fibrosis gene mutations in patients with CP. Recently, a point mutation (N34S) in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), was found in approximately 20% of patients with CP. The aim of our study was to determine the frequency of the N34S SPINKI gene mutation in a well-defined patient cohort with idiopathic CP (ICP) and to compare the incidence with healthy controls. In addition, we investigated the impact of this mutation on the long-term course of CP. METHODS: Fourteen patients with early-onset and four patients with late-onset CP of our well-defined pancreatitis cohort were enrolled in the present study, and 397 healthy individuals served as a control population. Coding exonic and the flanking intronic sequences of SPINK1 were investigated by direct DNA sequencing. The mutations found were confirmed by melting curve analysis. In addition, the N34S mutation was detected by analyzing the DNA fragments generated by digestion with restriction enzyme TspR I. Clinical data of patients with the N34S mutation were compared with those without mutations. RESULTS: The N34S mutation was detected in six of 14 (43%) patients with early-onset ICP. One patient was homozygous, and five patients were heterozygous for this mutation. The N34S mutation in a heterozygous state was found in four of 397 healthy controls (1.0%). The different allele frequency observed (seven of 28 vs four of 794) was significant (odds ratio = 66, 95% CI = 18-242, p < 0.0001). The clinical course was similar in patients with a mutation compared with those without a mutation. No other SPINKI mutations were detected. The N34S mutation was not found in patients with late-onset ICP. CONCLUSIONS: Our results indicate that the N34S mutation in the SPINKI gene is strongly associated with ICP, especially with the early-onset type. The natural course is similar in patients with mutations compared with SPINK1 mutation-negative patients. The N34S mutation may easily be screened for by restriction digestion with TspR I.

Adult↗