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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 199 records · Page 11Linked to original sources
PubMed1998

Pets are not a risk factor for Helicobacter pylori infection in young children: results of a population-based study in Southern Germany.

BACKGROUND: Helicobacter pylori may have multiple routes of transmission. It is unclear, however, whether the agent is also zoonotic and therefore transmitted from an animal reservoir. AIMS: The aim of this population-based study was to assess the relationship of exposure to pets and H. pylori infection among children in a population-based sample in Ulm, a city in the South of Germany. SUBJECTS AND METHODS: All children of German nationality who were to attend first grade in the school year 1996/1997 were included in the study. The 13C-urea breath test was used to determine active infection status. In addition the parents filled out a questionnaire to provide information about pets in the household as well as living conditions and socioeconomic factors of the family. RESULTS: Of 927 eligible preschool children 685 (74%) participated in the study. Prevalence of infection was 6.3%. Infection with H. pylori was not positively associated with contact with pets in general (p = 0.720) or to a specific kind of animal in bivariate and multivariable analyses as evaluated by means of logistic regression. CONCLUSIONS: These results suggest that pets in the household are not a risk factor for H. pylori infection among children in this population.

Animals↗
PubMed1998

Dyspepsia in relation to Helicobacter pylori infection and psychosocial work stress in white collar employees.

OBJECTIVE: We undertook an investigation of the relationship between psychosocial work stress and Helicobacter pylori (H. pylori) infection with dyspepsia. METHODS: We conducted a cross-sectional study among 189 employees of a health insurance company in the city of Ulm, Germany. RESULTS: A clear association between work-related psychosocial factors and the occurrence of dyspeptic symptoms during the past 3 months was evident. Persons who were considered to have a critical style of coping with work demands suffered more often from dyspeptic symptoms. Current infection with H. pylori was not associated with prevalence of dyspeptic symptoms. These results were also confirmed by adjustment for age, gender, smoking status, education, and use of antiinflammatory drugs within the past 3 months, by means of multivariate analysis. The odds ratio (OR) for having a dyspepsia symptom score in the upper tertile versus the 1st or 2nd was 3.22 (95% confidence interval [CI], 1.56-6.65), given that the employee was considered to have a critical style of coping with work demands. The OR for having a dyspepsia symptom score in the upper tertile given H. pylori infection was 1.23 (95% CI, 0.44-3.46), indicating no association of current H. pylori infection with dyspeptic symptoms. CONCLUSIONS: A critical style of coping with work demands may be an important determinant for dyspepsia-like symptoms. Therefore, in the absence of an underlying disease, specific intervention programs should be targeted at the behavior of the affected individual (e.g., stress-reduction programs) rather than on the treatment of specific symptoms or infection with H. pylori.

Adaptation, Psychological↗
PubMed1998

NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa.

NF-kappaB2 (p100/p52), a member of the NF-kappaB/Rel family of transcription factors, is involved in the regulation of a variety of genes important for immune function. Previously, we have shown that the NF-kappaB2 gene is regulated in a positive and a negative manner. Two kappaB elements within the NF-kappaB2 promoter mediate tumor necrosis factor alpha-inducible transactivation. In addition, we have shown that there exists a transcriptional repression in the absence of NF-kappaB. To identify a DNA binding activity responsible for this transcriptional repression, we have partially purified a nuclear complex, named Rep-kappaB. Here we further analyze this putative repressive binding activity. Detailed examination of Rep-kappaB-DNA interaction revealed the sequence requirements for binding to be almost identical to those of recombination signal binding protein Jkappa (RBP-Jkappa), the mammalian homolog of the protein encoded by Drosophila suppressor of hairless [Su(H)]. In addition, in electromobility shift assays, Rep-kappaB binding activity is recognized by an antibody directed against RBP-Jkappa. By performing transient-transfection assays, we show that human RBP-Jkappa represses basal as well as RelA (p65)-stimulated NF-kappaB2 promoter activity. Studies in Drosophila melanogaster have shown that Su(H) is implicated in the Notch signaling pathway regulating cell fate decisions. In transient-transfection assays we show that truncated Notch-1 strongly induces NF-kappaB2 promoter activity. In summary, our data clearly demonstrate that Rep-kappaB is closely related or identical to RBP-Jkappa. RBP-Jkappa is a strong transcriptional repressor of NF-kappaB2. Moreover, this repression can be overcome by activated Notch-1, suggesting that NF-kappaB2 is a novel putative Notch target gene.

DNA↗
PubMed1998

bax, but not bcl-2, influences the prognosis of human pancreatic cancer.

BACKGROUND: bcl-2 and bax belong to the bcl-2-related gene family, which marks a new class of genes that influence apoptosis. The bcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis. AIMS: To analyse the expression of bcl-2 and bax in pancreatic cancer and correlate the results with clinical parameters. PATIENTS: Pancreatic cancer tissue samples were obtained from 28 female and 32 male patients (median age 63, range 43-79 years) having surgery for pancreatic cancer. Normal pancreatic tissues obtained from 18 previously healthy organ donors served as controls. METHODS: The levels of bcl-2 and bax mRNA expression were analysed by northern blot and the exact site of mRNA transcription was determined by in situ hybridisation. The presence of the corresponding proteins was determined by immunohistochemistry. RESULTS: Northern blot analysis indicated that, in comparison with the normal pancreas, bcl-2 mRNA was overexpressed in 30% and bax mRNA in 61% of the pancreatic cancer samples. Concomitant overexpression of bcl-2 and bax was present in 26% of the cancer samples. Pancreatic adenocarcinomas exhibited 3.7-fold and 5.4-fold increases (p < 0.001) in bcl-2 and bax mRNA levels respectively. In situ hybridisation showed that both bcl-2 and bax mRNA were expressed in the cancer cells. Immunohistochemical analysis showed positive Bcl-2 and Bax immunostaining in 28 and 83% of the cancer samples respectively. In multivariate analysis (Cox regression model), bax expression was found to be a strong indicator of survival (p < 0.001). Patients whose tumours exhibited Bax immunostaining lived significantly longer (12 months) than those whose tumours were Bax negative (five months) (p < 0.039). In contrast, no relation was found between Bcl-2 and survival time. CONCLUSIONS: The data indicate that genes that are involved in the regulation of apoptosis are upregulated in human pancreatic cancer cells. Prolonged survival times in patients in whom apoptosis promoting factors are upregulated indicate that apoptotic pathways are of biological significance in pancreatic cancer.

Adolescent↗
PubMed1998

Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats.

Supramaximal stimulation of the pancreas with the CCK analog caerulein causes acute edematous pancreatitis. In this model, active trypsin can be detected in the pancreas shortly after the start of supramaximal stimulation. Incubation of pancreatic acini in vitro with a supramaximally stimulating caerulein concentration also results in rapid activation of trypsinogen. In the current study, we have used the techniques of subcellular fractionation and both light and electron microscopy immunolocalization to identify the site of trypsinogen activation and the subsequent fate of trypsin during caerulein-induced pancreatitis. We report that trypsin activity and trypsinogen-activation peptide (TAP), which is released on activation of trypsinogen, are first detectable in a heavy subcellular fraction. This fraction is enriched in digestive enzyme zymogens and lysosomal hydrolases. Subsequent to trypsinogen activation, both trypsin activity and TAP move to a soluble compartment. Immunolocalization studies indicate that trypsinogen activation occurs in cytoplasmic vacuoles that contain the lysosomal hydrolase cathepsin B. These observations suggest that, during the early stages of pancreatitis, trypsinogen is activated in subcellular organelles containing colocalized digestive enzyme zymogens and lysosomal hydrolases and that, subsequent to its activation, trypsin is released into the cytosol.

Acute Disease↗
PubMed1998

K-ras mutations at codon 12 are rare events in chronic pancreatitis.

BACKGROUND/AIMS: The activation of the K-ras gene at codon 12 is thought to be an early genetic event in the multistep pathogenesis of pancreatic cancer. Since the risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis, the aim of the present study was to determine the frequency of K-ras mutations in chronic pancreatitis. METHODS: Pancreatic DNA from intraoperatively resected tissues of 60 patients with chronic pancreatitis and 11 patients with histologically confirmed pancreatic carcinoma was evaluated by PCR amplification and restriction fragment length polymorphism analysis. RESULTS: In none of the 60 samples of chronic pancreatitis could K-ras mutations be identified using two independent PCR assays. In 5 of 11 patients with pancreatic carcinoma, K-ras mutations in codon 12 were detected. CONCLUSION: These data indicate that K-ras mutations are rare events in chronic pancreatitis. Alternatively, it is possible that the time span between the occurrence of K-ras mutations and malignant transformation is rather short.

Carcinoma↗
PubMed1998

Colon epithelium can be transiently transfected with liposomes, calcium phosphate precipitation and DEAE dextran in vivo.

BACKGROUND: The introduction of recombinant DNA into cells is the initial step toward the development of gene therapy. It has been shown that cationic liposomes are useful vehicles to introduce DNA into colon epithelial cells in vivo. METHODS: In the present study we compared the efficacy of different nonviral transfection methods into the colon wall. In anesthetized rats, a double balloon catheter was advanced into the colon and a chloramphenicol acetyltransferase (CAT) reporter plasmid complexed to liposomes, mixed with DEAE dextran, or precipitated with calcium phosphate was instilled. Following 2 days CAT activity was determined in the transfected colon segments. RESULTS: DEAE dextran and liposomes were more effective than calcium phosphate, whereas naked DNA was not taken up by the colon epithelial cells. Reporter gene expression was dose-dependent. Expressing cell types did not differ utilizing the various transfection methods as judged by X-gal staining of colon sections after transfection with a LacZ reporter plasmid. CONCLUSION: These data indicate that in addition to liposomes, plasmid DNA mixed with DEAE dextran can be taken up by colon epithelial cells. This transfection techniques may prove useful in the development of gene therapy approaches for colon disease.

Animals↗
PubMed1998

Helicobacter pylori and abdominal symptoms: a population-based study among preschool children in southern Germany.

OBJECTIVE: To determine the relation of Helicobacter pylori infection with gastrointestinal symptoms in a healthy population-based sample of children. DESIGN: Population-based cross-sectional study of preschool children. SETTING: Screening examination for school fitness by physicians of the Public Health Service in Ulm, a city with 100 000 inhabitants in southern Germany. PARTICIPANTS: One thousand two hundred one preschool children. MAIN OUTCOME MEASURES: Infection status was determined by 13C-urea breath test. Information on gastrointestinal symptoms was collected from children's parents by a standardized questionnaire and integrated into a symptom score. Results. Nine hundred forty-five children participated in the study (response rate, 79%). Overall, 127 children (13.4%) were infected. H pylori infection was not positively related to specific gastrointestinal symptomatology. Infected children had even fewer symptoms when compared with uninfected children. CONCLUSIONS: Our results indicate that H pylori infection in children is mostly asymptomatic and not associated with specific gastrointestinal symptoms.

Abdominal Pain↗
PubMed1998

[Analysis of polymorphisms Sma (Hpa II) and Sca I gene precursors of atrial natriuretic peptide (ANP) in patients with essential hypertension].

Both environmental and genetic factors are implicated in the pathogenesis of essential hypertension. The defect of the ANP precursor gene leading to the decrease of ANP synthesis are a cause of the development of sodium-sensitive hypertension in animals. Recent findings in African-Americans who are a model of sodium-sensitive population, reveal a strong association between Sma I polymorphism at intron 2 (the polymorphic site is identical for Hpa II restriction enzyme) or both Sma I and Sca I polymorphism at exon 3 of ANP precursor gene and essential hypertension. The aim of our study was to optimize the methods for Sma I and Sca I analysis in the ANP precursor gene (PCR followed by digestion with restriction enzymes) and to determine the frequencies of Sma I or Sca I genotypes and alleles in patients with sodium-sensitive (SS) or sodium-nonsensitive (SR) hypertension. The Sma I heterozygous mutation (WM genotype) were detected in 4 (8.9%) SS patients and in 2 (10%) patients in SR group. The frequency of Sca I M allele (allele with mutation) was significantly higher in SS group as compared to sodium-nonsensitive hypertensives. Our results suggest that, in contrast to Black hypertensives, in Caucasians with essential hypertension the Sma I polymorphism is very rare and the Sca I polymorphism of ANP precursor gene is associated with sodium-sensitivity of blood pressure.

Adult↗
PubMed1998

[MRCP (magnetic resonance cholangiopancreatography)--an assessment of current status].

For the first time, magnetic resonance cholangiopancretography (MRCP) provides images of the biliary and pancreatic ducts based on 3D data similar to those we are used to from endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Extraordinarily impressing is the fact that no contrast media have to be applied. The following manuscript shows technical basics and the development of this technique from gradient echo sequences to the recent single-shot techniques. Furthermore possibilities and limitations of MRCP will be discussed with respect to certain illnesses.

Bile Duct Neoplasms↗
PubMed1998

Calcitonin gene-related peptide mediates the protective effect of sensory nerves in a model of colonic injury.

Recently we demonstrated that sensory denervation with the neurotoxin capsaicin worsened the inflammation in an acute and chronic model of experimental colitis, which suggests a protective role of sensory nerve fibers during gut inflammation. Because we could demonstrate that sensory neuropeptides like Calcitonin gene-related peptide (CGRP) and substance P (SP) are released from sensory nerve fibers during intestinal inflammation, both are strong candidates as mediators for the protective effect of sensory neurons. In this study we investigate the role of CGRP and SP during experimental colitis in the rat by use of receptor antagonists against CGRP (CGRP 8-37, 1 microg/h continuous subcutaneous infusion), SP (RP67580, a NK-1 receptor antagonist, 3 mg/kg i.p.) and an immunoneutralizing CGRP-antibody. A mild colitis was induced by a rectal enema containing trinitrobenzenesulfonic acid. The severity of inflammation increased markedly after 7 days in the CGRP receptor antagonist and CGRP-antibody group compared with the vehicle group as determined by a macroscopic damage score (10.4 +/- 1.2 and 9.6 +/- 1.6 vs. 6.2 +/- 2.1) by a histologic ulceration score (82 +/- 8% and 73 +/- 6% vs. 42 +/- 23%) and by myeloperoxidase activity (19.2 +/- 6.8 and 18.1 +/- 5.9 vs. 8.6 +/- 5.3 U/mg tissue protein), respectively. Treatment with the specific SP receptor antagonist did not significantly alter the severity of colitis at 7 days compared with the control group. These data suggest that CGRP exerts mucosal protection during chronic experimental colitis.

Animals↗
PubMed1998

Parental smoking and infection with Helicobacter pylori among preschool children in southern Germany.

Exposure to parental smoking is known to increase children's susceptibility to a variety of infections. We investigated the relation of parental smoking to infection with Helicobacter pylori in a population-based study among preschool children who were screened for school fitness in the city of Ulm, Germany, in 1996. Current infection with H. pylori was measured by a 13C-labeled urea breath test. Information on factors potentially related to H. pylori infection, including parental smoking in the household, was obtained from children's parents through a self-administered standardized questionnaire. Among 1,201 eligible children, 945 participated in the study (response rate = 79%). Overall prevalence of active infection was 13.7%. After adjustment for confounding factors, we found a strong positive relation between smoking by the father in the household and H. pylori infection (odds ratio = 3.7; 95% confidence interval = 2.3-6.1). By contrast, there was a strong negative relation between smoking by the mother and H. pylori infection (odds ratio = 0.4; 95% confidence interval = 0.2-0.8) that was most pronounced among children who had been breastfed. These striking patterns cannot be explained by current knowledge.

Child↗
PubMed1998

[Possibilities of epidemiologic studies within the scope of school entrance examinations exemplified by Ulm Helicobacter pylori studies].

This paper illustrates the possibilities and the evidential value of epidemiologic studies in combination with the pre-school screening examinations, which in Germany are mandatory for all children who are to attend school for the first time. Aspects of study design and study conduct are discussed primarily. We used two studies conducted in the city of Ulm in 1996 and in 1997. The aim of these studies was to investigate the prevalence, determinants and effects of Helicobacter pylori infection among pre-school children and their parents. Study subjects were all pre-school children in Ulm, a city in the South of Germany, who were screened for school fitness by physicians of the Public Health Service in 1996 and 1997, respectively. Infection status was determined by 13C-urea breath test. In addition, the parents of the children were asked to fill out a standardized questionnaire. In the 1997 study, the infection status of the accompanying parents was also evaluated by 13C-urea breath test. We present some selected results from the study of 1996. In total 945 out of the 1201 eligible pre-school children participated in the study (response rate = 79%). Overall, 127 children (13.4%) were infected with Helicobacter pylori. The prevalence varied between 6.1% in the children with German nationality to 44.8% in children with Turkish nationality and 24.8% in children with other nationality. In addition, we identified further determinants and investigated effects of the infection. The results of these studies demonstrate that epidemiologic studies combined with the mandatory screening examinations in pre-school children may be an important and feasible way to gain knowledge. The participation of the Public Health Service is of special advantage and allows to collect health related data in a efficient way.

Adult↗
PubMed1998

Determination of 13CO2/12CO2 ratio by IRMS and NDIRS.

Breath tests using 13C-labelled substrates require the measurement of 13CO2/12CO2 ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the 13CO2/12CO2 ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1- 13C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning 13CO2-kinetics over longer time periods.

Breath Tests↗
PubMed1997

Cloning of novel transcripts of the human guanine-nucleotide-exchange factor Mss4: in situ chromosomal mapping and expression in pancreatic cancer.

In a previous large-scale analysis of gene expression in pancreatic cancer using gridded arrays of cDNA libraries and differential hybridizations, a gene that was a homolog to human mss4 was identified. Mss4 is a guanine-nucleotide-exchange factor for the Sec4/ Ypt1/Rab family of small GTP-binding proteins involved in the regulation of intracellular vesicular transport. By fluorescence in situ hybridization the human mss4 gene was assigned to chromosome 1q32-q41. Northern blot analysis revealed that three mss4 mRNA species are transcribed in human tissues of 780, 1200, and 2800 bp in length, respectively. Cloning and sequencing of the human mss4 transcripts from a pancreatic cancer cDNA library revealed that these mRNA species differ in the length of the 3-untranslated region and are probably due to the alternate use of polyadenylation sites. All mRNA species were detected at moderate to high levels in pancreatic cancer cell lines and were overexpressed in pancreatic cancer tissue compared to both normal pancreas and chronic pancreatitis tissue. However, the 1200-bp transcript was the Mss4 mRNA species with the highest level of expression in more than 50% of tumor cells and tissues. High levels of expression were found as well in other human tumor tissues. Mss4 as guanine-exchange factor required in the regulation of intracellular transport may be of importance for the function and growth of human tumor cells. However, the precise role of mss4 in human tumor cells is unknown and remains to be elucidated.

Amino Acid Sequence↗
PubMed1997

Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study.

OBJECTIVE: To assess the relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection. DESIGN: Cross sectional study of patients attending a general practitioner. Active H pylori infection was measured by the 15C-urea breath test and detailed quantitative information on smoking and on alcohol and coffee consumption was obtained by a standardised self administered questionnaire. SETTING: One general practice in Germany. SUBJECTS: 447 patients aged 15-79 who had not had peptic ulcer disease or treatment for H pylori infection. MAIN OUTCOME MEASURES: Prevalence of H pylori infection according to smoking and alcohol and coffee consumption. RESULTS: Overall prevalence of infection was 21% (94/447). There was no significant relation between smoking and active H pylori infection. Alcohol consumption showed a negative dose-response relation and coffee consumption a positive dose-response relation with active infection. After adjustment for potential confounders, the odds ratios for patients who drank < or = 75 g and > 75 g of ethanol a week compared with non-drinkers were 0.90 (95% confidence interval 0.55 to 1.59) and 0.33 (0.16 to 0.68), respectively (P value for trend 0.005, assuming that 1 litre of beer and 0.51 of wine contain on average 50 g of ethanol in south Germany). Adjusted odds ratios for patients who drank < 3 cups and > or = 3 cups of coffee per day compared with those who did not drink coffee were 1.49 (0.71 to 3.12) and 2.49 (1.23 to 5.03), respectively (P value for trend 0.007). CONCLUSION: These results suggest a protective effect of alcohol consumption against active infection with H pylori and an opposite effect of coffee consumption.

Adolescent↗