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A Bauer

Publications and source records attributed to A Bauer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families.

Recent studies have suggested that the alpha 7-nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7-nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13-14 regions. The human gene is partially duplicated (exons 5-10) with four novel upstream exons. The marker D15S1360 has been shown to be significantly linked with the phenotype of abnormal P50 suppression in schizophrenia families. The marker L76630 is 3 kb in the 3' direction from the last exon of the CHRNA7 gene and is located in the duplicated region. The function of the two L76630 copies is unknown. We genotyped three polymorphic markers D15S1360, D15S165, and L76630 that are localized in a genomic fragment containing the CHRNA7 in 31 Azorean schizophrenia families/trios (including 41 schizophrenia individuals and 97 unaffected families members). An overall analysis utilizing the family-based association test revealed significant linkage disequilibrium between L76630 and schizophrenia (P = 0.0004). Using the extended transmission disequilibrium test and limiting the analysis to one triad per family, transmission disequilibrium of D15S1360 was near significance (P = 0.078). The 15q13 region overlaps with the location of two well-known genomically imprinted disorders: Angelman syndrome and Prader-Willi syndrome. Therefore, we investigated maternal and paternal meioses. We found significant transmission disequilibrium for D15S1360 through paternal transmission (P = 0.0006) in our schizophrenia families. The L76630 marker showed a significant disequilibrium in maternal transmissions (P = 0.028). No parent-of-origin effect was found in D15S165. Overall, our results suggest that the CHRNA7 may play a role in schizophrenia in these families. A parent of origin effect may be present and requires further study.

Alleles↗
PubMed2001

Time-resolved laser fluorescence spectroscopy study of the sorption of Cm(III) onto smectite and kaolinite.

For long-term performance assessment of nuclear waste repositories knowledge concerning interactions of actinides with mineral surfaces is imperative. The mobility and bioavailability of released radionuclides is strongly dependent on sorption/desorption processes onto mineral surfaces. Therefore it is necessary to characterize the surface species formed and to elucidate the reaction mechanisms involved. The high fluorescence spectroscopic sensitivity of Cm(III) has attracted our interest regarding the complexation process of Cm(III) onto smectite and kaolinite as a model system for the sorption of trivalent actinides in the trace concentration range. We conclude that at low pH Cm(III) is sorbed onto kaolinite and smectite as an outer-sphere complex and retains its complete primary hydration sphere. With increasing pH inner-sphere adsorption onto kaolinite and smectite occurs via the aluminol edge sites. The same evolution of the Cm(III)-clay surface species as a function of pH was observed for both minerals. Starting at a pH > or = 5 we observe the formation of a [triple bond]Al-O-Cm2+(H2O)5 surface complex, which is replaced by a second species at higher pH. The second surface complex may be a monodentate [triple bond]Al-O-Cm+(OH)(H2O)4 species or bidentate [triple bond](Al-O)2-Cm+(H2O)5 species. The Cm(III)/clay surface complexes are characterized bytheir emission spectra (peak maxima at 598.8 and 603.3 nm) and their fluorescence lifetime (both 110 +/- 7 micros). An important result in view of the mobility and bioavailability of radionuclides is that no incorporation of Cm(III) into the bulk clay structure was observed.

Adsorption↗
PubMed2001

CREB regulates hepatic gluconeogenesis through the coactivator PGC-1.

When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon and glucocorticoids. The pathways act synergistically to induce gluconeogenesis (glucose synthesis), although the underlying mechanism has not been determined. Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hypoglycaemia [corrected] and reduced expression of gluconeogenic enzymes. CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo. Overexpression of PGC-1 in CREB-deficient mice restored glucose homeostasis and rescued expression of gluconeogenic genes. In transient assays, PGC-1 potentiated glucocorticoid induction of the gene for phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. PGC-1 promotes cooperativity between cyclic AMP and glucocorticoid signalling pathways during hepatic gluconeogenesis. Fasting hyperglycaemia is strongly correlated with type II diabetes, so our results suggest that the activation of PGC-1 by CREB in liver contributes importantly to the pathogenesis of this disease.

Adenoviridae↗
PubMed2001

Intercaval block in normal canine hearts : role of the terminal crest.

BACKGROUND: The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities. METHODS AND RESULTS: To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10x10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S(1)S(1)=200 ms) and introduction of up to 2 extrastimuli (S(2), S(3)). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1+/-0.4 versus 0.5+/-0.2 m/s, P<0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5+/-0.3 versus 0.6+/-0.2 m/s, P=NS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not >30 ms. During S(3) stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region. CONCLUSIONS: Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.

Animals↗
PubMed2001

Smallest region of overlapping deletion in 1p36 in human neuroblastoma: a 1 Mbp cosmid and PAC contig.

In human neuroblastomas, the distal portion of 1p is frequently deleted, as if one or more tumor suppressor genes from this region were involved in neuroblastoma tumorigenesis. Earlier studies had identified a smallest region of overlapping deletion (SRO) spanning approximately 23 cM between the most distally retained D1S80 and by the proximally retained D1S244. In pursuit of generating a refined delineation of the minimally deleted region, we have analyzed 49 neuroblastomas of different stages for loss of heterozygosity (LOH) from 1pter to 1p35 by employing 26 simple sequence length polymorphisms. Fifteen of the 49 tumors (31%) had LOH; homozygous deletion was not detected. Seven tumors had LOH at all informative loci analyzed, and eight tumors showed a terminal or an interstitial allelic loss of 1p. One small terminal and one interstitial deletion defined a new 1.7 cM SRO, approximately 1 Mbp in physical length, deleted in all tumors between the retained D1S2731 (distal) and D1S2666 (proximal). To determine the genomic complexity of the deleted region shared among tumors, we assembled a physical map of the I Mbp SRO consisting predominantly of bacteriophage P1-derived artificial chromosome (PAC) clones. A total of 55 sequence-tagged site (STS) markers (23 published STSs and short tandem repeats and 32 newly identified STSs from the insert ends of PACs and cosmids) were assembled in a contig, resulting in a sequence-ready physical map with approximately one STS per 20 Kbp. Twelve genes (41BB, CD30, DFFA, DJ1, DR3, FRAP, HKR3, MASP2, MTHFR, RIZ, TNR2, TP73) previously mapped to 1p36 are localized outside this SRO. On the basis of this study, they would be excluded as candidate genes for neuroblastoma tumorigenesis. Ten expressed sequence tags were integrated in the contig, of which five are located outside the SRO. The other five from within the SRO may provide an entrance point for the cloning of candidate genes for neuroblastoma.

Bacteriophage P1↗
PubMed2001

Comparative analysis of human, bovine, and murine Oct-4 upstream promoter sequences.

The Oct-4 gene encodes a transcription factor that is specifically expressed in embryonic stem cells and germ cells of the mouse embryo. Cells that differentiate into somatic tissues lose Oct-4 expression. Regulation of Oct-4 gene transcription involves a TATA-less minimal promoter and two upstream elements: the proximal (PE) and distal enhancers (DE). We report here the nucleotide sequence of the 5' upstream regulatory regions of the human and murine Oct-4 genes. A comparative alignment analysis between these regions and those of the bovine Oct-4 ortholog reveals four conserved regions of homology (CR 1 to 4) between these species (66-94% conservation). The 1A sequence within the mouse PE is located approximately half-way between CR 2 and CR 3. A putative Sp1/Sp3 binding site and the overlapping hormone responsive element (HRE) in CR1 are identical in all three species. A high number of CCC(A/T)CCC motifs exhibit various levels of homology in these upstream regions. We discuss the importance of these and other sequences and present candidate factors that may bind and regulate Oct-4 gene expression.

Animals↗
PubMed2001

[Predictive value of frequency, duration and rate of ventricular salvos in ambulatory ECG for inducibility of sustained ventricular tachycardia].

Identification of high risk patients with coronary artery disease (CAD) prone to sudden cardiac death still remains a difficult issue. In 211 patients with CAD diagnosed by coronary angiography and documented non-sustained ventricular tachycardia (NSVT), programmed ventricular stimulation (PVS) was performed. NSVTs documented during Holter monitoring were analysed concerning frequency, duration and rate. To relate those parameters to the inducibility of sustained monomorphic ventricular tachycardias (MVT) during PVS, the total population was divided in different groups; patients with 1, 2-5 or > 5 salvos within 24 h; patients having salvos with a rate of > or = 150/min or < 150/min; patients with 3-5, 6-10 or > 10 consecutive extra beats. It could be demonstrated that in patients with CAD and NSVTs, induction of MVTs during PVS is more likely if the rate of the spontaneously occurring NSVT is > or = 150/min (22.1 vs 8.9%; p = 0.042). In contrast, there is apparently no correlation between the duration and incidence of NSVTs and the prevalence of MVTs during PVS. Multivariate analysis revealed the rate of documented NSVTs (odds ratio 2.98, p = 0.0314) and a decrease of left ventricular ejection fraction (odds ratio 1.69; p = 0.0013) as independent risk factors for the inducibility of MVTs. Conclusions CAD patients with fast salvos (> or = 150 beats/min) and reduced left ventricular ejection fraction are more likely to reveal inducible MVT during PVS and should, therefore, preferably be subjected to invasive risk stratification. The number of salvos per day and the number of consecutive beats, on the other hand, do not seem to be of relevant predictive value.

Aged↗
PubMed2001

Effect of radiofrequency ablation on atrial myocardium.

OBJECTIVES: Successful RF ablation of atrial fibrillation supposedly requires the creation of continuous linear lesions. This study aimed to determine the potential role of functional modifications of atrial myocardium in the vicinity of anatomic RF lesions. METHODS: In 10 normal beagles (group A), a multiplexer mapping system and an epicardial multi-electrode were used to reconstruct atrial activation patterns during pacing at two cycle lengths before and after attempts to induce two linear right atrial lesions with a standard ablation catheter, respectively. An intercaval "drawback" was repeated 3 times over 5 min at a set temperature of 70 degrees C, followed by a transversal "point-by-point" ablation from the interatrial septum to the right-lateral tricuspid annulus at 70 degrees C/60 s each. Induction of atrial flutter was attempted before and after each ablation. In another 6 beagles (group B), a high-resolution multi-electrode was used to study epicardial functional effects resulting from single endocardial RF lesions on the free right atrial wall. Using three energy settings (60 degrees C/30 s, 60 degrees C/60 s, 70 degrees C/60 s), activation patterns were analyzed at two cycle lengths and local effective refractory periods were measured across the lesion. RESULTS: The lesions induced in group A only marginally affected atrial activation patterns and total activation times. However, as shown in dogs with atrial flutter, regional slow conduction was enhanced and functional conduction blocks were facilitated at high atrial rates, resulting in a significant prolongation in the revolution time of respective reentrant circuits. Apart from inducing anatomic lesions, single endocardial RF lesions (group B) were shown to delay epicardial conduction in adjacent myocardium in an energy- and rate-dependent way. Furthermore, an energy-dependent prolongation of effective refractory periods by far exceeding the size of anatomic lesions was observed. CONCLUSIONS: Continuous linear atrial lesions are hard to achieve with conventional ablation techniques. However, RF lesions induce changes in conduction and refractoriness around the anatomic lesion, which are likely to contribute to the overall effect of respective therapeutic interventions.

Animals↗
PubMed2001

Effects of propafenone on anisotropic conduction properties within the three-dimensional structure of the canine ventricular wall.

BACKGROUND: Structural complexities of the intact ventricular wall cause a very complex spread of activation. The effects of regional tissue damage and of antiarrhythmic drugs on directional differences in activation should help to further elucidate intramural conduction patterns. METHODS AND RESULTS: In 10 healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were inserted into the left anterior ventricular wall. Using a computerized multiplexer-mapping system, the spread of activation in epi-, endo- and midmyocardial muscle layers and in the surviving epicardium, respectively, was reconstructed. Marked differences in conduction velocities relative to fiber orientation were evident in the surviving epicardium of infarcted hearts. Directional differences in conduction velocities, although less pronounced, were still preserved throughout the intact ventricular wall. Epicardial transverse conduction in intact hearts was significantly faster than transverse conduction in infarcted hearts (0.87 +/- 0.11 m/s vs 0.68 +/- 0.1 m/s). In normal hearts, propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal directions (-27 +/- 10%), but also moderately in transverse directions (-13 +/- 7 %) of all muscle layers, with no significant effect on straight (-4 +/- 8 %), but on oblique transmural conduction (-33 +/- 18 %). In infarcted hearts propafenone decreased conduction particularly in longitudinal direction (-23 +/- 14 %) without affecting conduction transverse to the fiber orientation (+3 +/- 6%). CONCLUSIONS: Longitudinal intramural shortcircuits reduce directional differences in activation. Transmural infarction results in a loss of alternative intramural pathways, unmasking marked anisotropy in the surviving epicardium. Conduction delay in intramural pathways explains the effects of propafenone on transverse and oblique transmural conduction. Primarily longitudinal conduction delay results in reduced tissue anisotropy.

Animals↗
PubMed2001

The relevance of stereopsis for motorists: a pilot study.

PURPOSE: To study the influence of stereoscopic depth perception on automobile driving performance. METHODS: Ten patients with strabismus and defective stereopsis were compared with ten healthy controls with respect to their performance in a series of automobile driving manoeuvres. The two groups were individually matched as to age, annual miles driven, years of licence holding and type of vehicle owned. After an ophthalmologic examination the subjects in each group performed the following series of driving tests: (1) stopping in front of an obstacle, (2) reversing into a parking space, (3) driving through a slalom course, (4) estimating the relative positions of two cars. All tests were performed binocularly and monocularly (with the non-dominant eye covered). RESULTS: Only in the slalom test did the normal subjects perform significantly better than the stereo-deficient subjects (odds ratio 10.5; P<0.01). In estimating position, normal subjects actually performed significantly worse (odds ratio 0.091; P<0.01). A significant distance ratio of 2.5 (95% CI 1.1-5.5; P=0.033) of the monocular with respect to the binocular performance of the normal subjects was found for the stopping task only, while the subjects with defective stereopsis showed no difference between their monocular and binocular performance. CONCLUSION: In this study, stereopsis had a positive effect on driving performance only in dynamic situations at intermediate distances.

Adult↗
PubMed2001

Occupational hand dermatitis in food industry apprentices: results of a 3-year follow-up cohort study.

OBJECTIVE: The aim of this prospective follow-up study was to quantify the impact of hand dermatitis (HD) in bakers, confectioners and bakery shop assistants, and to investigate related risk factors. METHOD: Bakers', confectioners' and bakery-shop assistants were included in a prospective follow-up study in the region of East Thuringia starting in August 1996. At the beginning of their vocational training 91 apprentices were interviewed and examined in a standardised way. Follow-up examinations and interviews were done after 6 months (n = 79), 12 months (n = 63) and at the end of the training (n = 69) after 36 months. RESULTS: In their case histories 3.3% (n = 3) of the apprentices reported previous HD in childhood and adolescence. The first assessment after 2 to 4 weeks of vocational training revealed HD in 17.5% (n = 16) of the individuals. At the follow-up examination after 6 months, point prevalence of HD was 29.1% (n = 23), after 12 months 27.0% (n = 17) and after 36 months 27.5% (n = 19). Mild to moderate irritant contact dermatitis was the most frequent finding. Finally, an atopic skin diathesis (> 10 points, "atopy score") (OR = 4.89; CI 95% 1.15-20.79), previous HD (OR = 41.1; CI 95% 4.99-339.13) as well as flexural dermatitis (OR = 6.8; CI 95% 1.72-27.22) proved to be predictive factors for the development of HD. No association was found to respiratory atopy (OR = 1.29; CI 95% 0.35-4.7) and metal sensitisation (OR = 1.1; CI 95% 0.29-4.35). Exogenous irritant factors did not show a strong association towards a risk increase. Wet work in general, as well as distinct occupational tasks showed only a tendency for being a risk factor for HD. However, leisure time activities, especially house building and rebuilding (OR = 5.4; CI 95% 1.05-27.81), were associated with an elevated risk. CONCLUSIONS: Endogenous and exogenous factors contribute to the development of HD in bakers' and confectioners' apprentices.

Adolescent↗
PubMed2001

Trends and developments in public psychiatry in France since 1975.

OBJECTIVE: The authors present an account of the current state of sectorization in France and its development over the last decade. METHOD: The paper is based on statistics collected by the French Health Ministry and on relevant laws and regulations. Comments by patients, families and professionals are presented. RESULTS: The supply of mental health care is usually satisfactory, and there is a tendency for in-patient units to be converted into day hospitals. There is a large disparity between regions, especially in child and adolescent psychiatry. The 1838 law governing compulsory admissions was revised in 1990, and this revision was the object of a commission of inquiry in 1995. Psychiatric units work on the borders between health and social services and are forging new links between the two. CONCLUSION: Psychiatric care requires an integrated health and social perspective. In the field of mental health legislation European recommendations are called for.

Commitment of Persons with Psychiatric Disorders↗
PubMed2001

The prevention of occupational hand dermatitis in bakers, confectioners and employees in the catering trades. Preliminary results of a skin prevention program.

Occupational skin diseases (OSD) are among the most frequent occupational diseases (OD). Compared to other occupations, bakers, confectioners and employees in the catering trades are at a high risk of developing OSD. In January 1999, the interdisciplinary Skin Disease Prevention Program in the Baking, Hotel and Catering Industries (SDPP) conducted by the Department of Dermatology and Allergology at the Friedrich Schiller University, Jena, in cooperation with the Research Center for Applied System Safety and Industrial Medicine, Erfurt, and the technical experts at the Social Insurance for the Food Industry and Related Professions (Berufsgenossenschaft für Nahrungsmittel und Gaststätten--(BGN)), Erfurt, was initiated. Following detailed analysis of the occupational exposure of the employees and their personal occupational disease history, the patients' diagnosis and therapy was re-evaluated and supplemented if necessary. Individual skin care and protection regimes were demonstrated and practically trained. Skin care and protection products were supplied. Skin-care and protection seminars were offered to volunteering participants. From January to December 1999, 29 affected employees were examined in the OSD clinic. 22 employees (76%) suffered from irritant contact dermatitis. The follow-up data of 11 employees are available. In 8 employees (73%), the skin disease improved or disappeared. Moreover, in 1 employee (9%), the skin condition was stabilized even though he continued working. In only 2 employees (18%) did the skin condition worsen. These preliminary results showed that most of the OSD were due to lack of or unsuitable skin care and protection. The program will be extended to cover a larger number of food industry employees with OSD.

Adolescent↗
PubMed2001

[Evaluation of environmental medicine documentation in Schleswig-Holstein 1995-1999].

Physicians qualified in environmentally related disorders due to their participation in special training courses in the Federal State of Schleswig-Holstein (Germany) used a standardised questionnaire to report on their environmental medicine related cases. The course of the illness, if known, has been documented on a separate data sheet. During the period from 1995-1999 916 cases and 508 courses of illness were assessed. The environmental factors/toxicants of exposure most frequently documented by the 85 participating physicians and found to be related to symptoms of illness were biocides (mainly insecticides used indoors for pest control (32%), moulds (27%), dental amalgam (22%), solvents/volatile organic compounds (21%) and formaldehyde (16%), respectively. In 42% of the documented cases an exposure to more than one environmental factor/toxicant was registered. Age distribution, gender, location of exposure as well as the symptoms of illness of the patients were found to be dependent on the type of exposure. Cessation of exposure to harmful substances/environments was achieved in 54% of those cases where information regarding the course of the illness was given. In 65% of these cases recovery was reported and 30% recovered partially. In those cases where a cessation of exposure could not be achieved or was not complete, no or only partial recovery was mostly reported. From these results it may be concluded that research work on environmentally related disorders should be enforced in order to prevent unnecessary illness and to lower the public health system expenditure.

Adolescent↗
PubMed2001

[Breast cancer mortality in women in the Schleswig-Holstein district 1981 to 1995].

The present descriptive study evaluates breast cancer mortality among women in the northernmost German Federal State of Schleswig-Holstein over the period from 1981 to 1995 based on data provided by the Schleswig-Holstein State Office for Statistics. Starting from the results of the second Cancer Atlas for the Federal Republic of Germany [11], covering the period 1976-1980, breast cancer mortality rates rose sharply until the beginning of our investigation. A moderate rise in breast-cancer mortality in Schleswig-Holstein continued until the third period under investigation (1987-1989), while after that time breast cancer mortality decreased again towards the end of the investigation period. In Schleswig-Holstein as a whole, the mortality rate increased by approximately 12% during the last 20 years. When reviewing age-specific breast-cancer mortality for each rural district ('Kreis') or, respectively, for each self-administrative town (kreisfreie Stadt), different patterns were observed, particularly among younger women. In the 40- to 44-year and 45- to 49-year age group a rise in breast cancer mortality was observed in several, but not all districts. Mortality patterns do not tend to be representative for breast cancer incidence because mortality reflects only a small proportion of the women actually suffering from breast cancer. The standardised incidence of breast cancer in Germany--calculated on the basis of data provided by the Saarland cancer registry--is currently over 60/100,000 and is thus 2-3 times the mortality rate. However, presently it is not possible to evaluate the breast cancer incidence (Schleswig-Holstein) because the first population-based cancer registration was initiated only in 1999. In contrast to other German Federal States, notification of all cancer cases is compulsory in Schleswig-Holstein. A valid analysis of breast cancer incidence should be possible in 5-10 years conditional on a registration rate of at least 90%. Further investigations into the causes of breast cancer should be carried out to test specific hypotheses on exposure to risk factors, including nutrition and life style to clarify the regional differences observed in this study.

Adult↗
PubMed2001

[Hereditary pancreatitis - a clinically relevant cause of pancreatic adenocarcinoma?].

UNLABELLED: Hereditary pancreatitis is an autosomal dominant disease. Recently, the genetic defect has been mapped to chromosome 7q35 and consists mainly of a point mutation in exon 3 of the cationic trypsinogen gene which causes an Arg(CGC)-His(CAC) substitution at residue 117. In patients with hereditary pancreatitis the estimated cumulative risk for pancreatic carcinoma to age 70 approaches 40 %. Thus, the role of hereditary pancreatitis in the pathogenesis of pancreatic carcinoma is of interest. PATIENTS AND METHODS: DNA was extracted from peripheral blood (n = 16), fresh tumor tissue (n = 29) and formalin fixed and paraffin embedded tumor tissue (n = 5) of 50 patients with ductal adenocarcinoma of the pancreas. We specifically amplified exon 3 and the intronic flanking sequences of the cationic trypsinogen gene by nested PCR and performed restriction fragment length polymorphism analysis using the restriction enzyme Afl III. In patients with hereditary pancreatitis the G : A point mutation creates a recognition site for Afl III which is not present in unaffected individuals. RESULTS: None of the 50 patients with ductal adenocarcinoma of the pancreas revealed the G : A point mutation in exon 3 of the cationic trypsinogen gene which is characteristic of hereditary pancreatitis. In addition sequencing of exon 3 did not reveal any other mutations in the DNA of patients with pancreatic adenocarcinoma. CONCLUSION: Although hereditary pancreatitis markedly increases the risk for pancreatic cancer, it is rare and probably of little significance with respect to the pathogenesis of the majority of pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed2001

Modulation of endogenous nitric oxide synthase in experimental acute pancreatitis: role of anti-ICAM-1 and oxygen free radical scavengers.

OBJECTIVE: To evaluate, in an experimental model of acute pancreatitis, the impact of nitric oxide on the disease process and the interaction between nitric oxide and oxygen free radicals. SUMMARY BACKGROUND DATA: Nitric oxide and oxygen free radicals are involved in the pathophysiology of acute pancreatitis. It is well established that oxygen free radicals play an important role in the development of pancreatic cell damage and remote organ failure, but the impact of nitric oxide on the disease process and the interactions between the two radical species remain controversial. METHODS: Necrotizing pancreatitis (NP) was induced in Wistar rats by intraductal sodium taurocholate infusion after pretreatment with isotonic saline (NP-S), superoxide dismutase/catalase (NP-SOD/CAT), or an anti-ICAM-1 antibody (aICAM-1). Sham-operated rats received isotonic saline (SHX). After an observation period of 5 minutes and 24 hours, the pancreas was removed for microscopy, glutathione, and myeloperoxidase (MPO) analysis. The inducible NO synthase (NOS-2) was detected by Western blotting or RT-PCR. Serum was analyzed for nitrite/nitrate (NO2-/NO3-) and S-nitrosothioles (RSNO), while plasma was used to assay for trypsinogen activation peptides (TAP). RESULTS: NP-S animals showed a significant decrease in GSH levels after NP-induction as compared with animals under therapy. Increased MPO levels in the NP-S group were significantly reduced by aICAM-1 while SOD/CAT injection showed no changes. Serum NO-derivatives peaked at 12 hours while TAP levels had a maximum at 6 hours after NP induction, and were lower after aICAM-1 application SOD/CAT treatment increased both parameters. Extended acinar cell damage and inflammatory infiltrate developed in NP-S animals and was significantly improved by SOD/CAT and aICAM-1 treatment. RT-PCR and Western-blot analysis revealed NOS-2 expression in the NP-S group, which was reduced by radical scavengers and aICAM-1. CONCLUSION: Enhanced nitric oxide synthase expression and increased nitric oxide derivatives are found during severe acute pancreatitis. Oxygen free radicals and neutrophils seem to be potent and important regulation mechanisms for nitric oxide synthase activity and nitric oxide-mediated toxicity but imply only a secondary role for nitric oxide in the local pathologic mechanism of this disease.

Animals↗