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G Seitz

Publications and source records attributed to G Seitz.

At least 19 recordsLinked to original sources
PubMed2006

MALT lymphoma associated genetic aberrations occur at different frequencies in primary and secondary intestinal MALT lymphomas.

BACKGROUND AND AIMS: Limited data are available on intestinal MALT lymphoma owing to its relatively rare occurrence. The frequency of associated genetic changes was therefore analysed in intestinal MALT lymphoma to determine whether primary and secondary examples may be distinguished by their genetic profile. METHODS: Patients diagnosed with MALT lymphoma involving the intestine were evaluated and compared with 71 cases with localised gastric MALT lymphoma. Paraffin embedded samples were evaluated for t(11;18)(q21;q21) by reverse transcription polymerase chain reaction, and by fluorescence in situ hybridisation for t(14;18)(q32;q21), t(1;14)(p22;q32), and trisomies 3 and 18. RESULTS: 30 consecutive patients with MALT lymphoma involving the intestine were identified: 16 had primary intestinal lymphoma and 14 had secondary MALT lymphoma. t(11;18)(q21;q21) was found in one third of the patients, but there was a significant difference between the secondary MALT lymphomas and the primary intestinal and gastric MALT lymphoma groups (57% v 12.5%, p = 0.019, and 57% v 24%, p = 0.022). Two patients with primary intestinal MALT lymphomas were positive for t(1;14)(p22;q32) and none was positive for t(14;18)(q32;q21). Primary intestinal MALT lymphoma had a significantly higher frequency of trisomies 3 or 18 (81% v 36%, p = 0.024; 81% v 14%, p<0.001), in contrast to secondary intestinal MALT lymphomas and localised gastric MALT lymphomas. CONCLUSIONS: The genetic profile of primary intestinal MALT lymphomas appears to be different from that of secondary intestinal or local gastric MALT lymphomas. Because of the high prevalence of trisomy 3 or 18, or both, in primary intestinal lymphoma, these numerical aberrations might be regarded as a genetic hallmark of the disease.

Adult↗
PubMed2006

Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a randomized, double-blind, placebo-controlled multicentre trial.

BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.

Adult↗
PubMed2005

Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer.

Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies.

Adenocarcinoma↗
PubMed2005

Curative treatment for high-grade intraepithelial neoplasia in Barrett's esophagus.

BACKGROUND AND STUDY AIMS: The incidence of premalignant and malignant lesions in specialized intestinal metaplasia of the esophagus has increased dramatically in the industrialized world in recent years. This report evaluates the efficacy and safety of local endoscopic therapy for high-grade intraepithelial neoplasia (HGIN) in Barrett's esophagus. PATIENTS AND METHODS: Over a 5-year period between October 1996 and September 2001, a total of 379 patients were referred with a suspicion of early Barrett's cancer. In a prospective study, 44 patients with HGIN in Barrett's esophagus were selected for local endoscopic treatment. Endoscopic resection was carried out in 14 patients in whom the HGIN was re-detectable, and 27 patients in whom the HGIN was not re-detectable underwent photodynamic therapy (PDT). Endoscopic resection and PDT were combined in three patients. RESULTS: Complete remission was achieved in 43 of the 44 patients (97.7 %). No major complications occurred. A mean of 1 session was needed to achieve complete local remission. During a mean follow-up period of 36 months (range 7 - 61 months), recurrent or metachronous lesions were observed in six patients (17.1 %), all of whom received a second successful endoscopic treatment. CONCLUSIONS: Endoscopic therapy is a safe alternative treatment regimen for HGIN in Barrett's esophagus, providing a middle way between the widely promulgated options of a "watch-and-wait" policy and radical esophagectomy.

Adult↗
PubMed2004

Novel enantiopure ferrugininoids active as nicotinic agents: synthesis and radioligand binding studies.

A series of hitherto unknown enantiopure (-)-ferruginine analogues of type 8 and 9 was prepared and tested for the affinity toward the nicotinic acetylcholine receptor (nAChR) subtypes (alpha4)2(beta2)3, alpha7*, alpha3beta4*, and (alpha1)2beta1gamma delta. The stereoconservative asymmetric syntheses started with (-)-cocainhydrochloride (10) from the chiral pool which was transformed into the chiral building blocks (+)-2-tropanone (11) and to (-)-anhydroecgonine (18). Key steps of the syntheses are novel extensions to existing methodology e.g. a Suzuki Pd(0)-mediated cross-coupling of vinyl triflate (12) with the heteroaryl organoboranes 13-15 and an inverse type [4+2]-cycloaddition with 1,2,4,5-tetrazine (21). The bioisosteric replacement of the 3-acetyl pharmacophoric element of the lead 6 by a 3-pyridyl, 5-chloropyridyl, 5-pyrimidinyl, 2-pyrazinyl, or 4-pyridazinyl moiety resulted in nAChR ligands with Ki-values ranging from 1.1-713 nM toward the (alpha4)2(beta2)3 subtype combined with significant differentiation among the nAChR subtypes when tested in vitro by radioligand binding studies. Generally the ferrugininoids are less potent than the corresponding norferrugininoids. Similar to results of the norferrugininoid series the novel azine substituted ferrugininoids 8 proved to be more potent than the diazine analogues 9; both exhibited higher affinities compared to the lead 6. The 5-chloropyridyl-containing variant 8b [1R, 5S)-enantiomer] turned out to be the most active nAChR ligand with a 12-fold higher affinity toward the (alpha4)2(beta2)3 subtype than the corresponding (1S, 5R)-form ent-8b.

Animals↗
PubMed2003

Histopathological diagnosis of Barrett's mucosa and associated neoplasias: results of a consensus conference of the Working Group for Gastroenterological Pathology of the German Society for Pathology on 22 September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was, therefore, the aim of a consensus conference of the Working Group for Gastroenterological Pathology within the German Society of Pathology to achieve standardisation regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗
PubMed2003

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001].

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗
PubMed2003

Sonographic diagnosis of a carcinoid tumour of the appendix in a 14-year-old boy.

Carcinoid tumours of the appendix are rare tumours of the bowel which occasionally are found histologically in resected appendices. There are no publications on the sonographic diagnosis of carcinoid tumours of the appendix in children. We report on the sonographic examination of a carcinoid tumour in a 14-year-old boy. Sonography showed a hypoechoic tumour located at the apex of the appendix with eccentric growth. Histology revealed a carcinoid tumour with invasion of the regional lymphatic vessels.

Adolescent↗
PubMed2003

Oral budesonide significantly improves water absorption in patients with ileostomy for Crohn disease.

BACKGROUND: In addition to their anti-inflammatory effects, steroids influence electrolyte and water transport systems in the intestinal mucosa. This study analysed the effect of the topically acting glucocorticoid budesonide on ileostomy output in patients with Crohn disease. METHODS: Oral budesonide (3 mg/three times daily for 8 days; n = 20) was compared to placebo (n = 20) in a double-blind design using matched-pair randomization according to ileal resection length in patients without detectable inflammatory activity. Under controlled hospital conditions, absolute output volumes were measured and response was defined as a reduction in intestinal output of > 25% compared to pretreatment conditions. RESULTS: In the treatment group, we observed an absolute decrease in median intestinal output from 1,240 ml to 865 ml (30.2%), compared to 0.3% under placebo (from 950 ml to 947.5 ml). Response was documented in 60% (12/20 patients) in the treatment group compared to no response under placebo (P < 0.0001). While both treatment groups showed similar absolute median reductions (400 ml with ileal resection < or = 20 cm and 405 ml with ileal resection > 20 cm), the relative reduction (response rate) was lower in the subgroup of an ileal resection > 20 cm (36%) due to the greater increase in output secondary to the loss of ileum. CONCLUSIONS: These data support the assumption that the absorptive capacity of the intestinal mucosa for water may be improved by topically acting steroids and suggest that this occurs independently of their anti-inflammatory effect.

Administration, Oral↗
PubMed2003

Late pulmonary metastasis in uterine PEComa.

Perivascular epithelioid cell tumours (PEComas) other than angiomyolipoma, clear cell "sugar" tumour of the lung, and lymphangioleiomyomatosis are very rare mesenchymal tumours. The uterus seems to be the most prevalent site of involvement, but only 13 cases of uterine PEComa have been described. Three of these cases exhibited local aggressive behaviour and only one showed metastasis. Because of the extremely small number of cases, PEComas are considered tumours of uncertain malignant potential. This report describes a 68 year old woman, who presented with multiple pulmonary lesions seven years after the initial diagnosis of well differentiated endometrial stromal sarcoma. Histological and immunohistochemical analysis of the pulmonary lesions, in addition to re-evaluation of the primary uterine tumour, led to the final diagnosis of metastatic uterine PEComa. The findings indicate that any PEComa might have malignant potential. Spreading of this tumour to other organs might become evident even several years after primary manifestation.

Actins↗
PubMed2003

Synthesis and nicotinic binding studies on enantiopure pinnamine variants with an 8-azabicyclo[3.2.1]octane moiety.

Bioisosteric replacement of the 9-azabicyclo[4.2.1]nonane pharmacophoric element of the novel alkaloidal marine toxine pinnamine (5) by the 8-azabicyclo[3.2.1]octane moiety resulted in conformationally restricted analogues 6a and 6c of (-)-ferruginine (4). Key step in the diastereoselective synthesis of these pyranotropanes was the condensation of enantiopure ecgonine methyl ester (9) from the "chiral pool" with the lithium anion of N-tert-butylbutyraldimin and subsequent cyclisation with TFA. The potential nAChR ligands were tested for their in vitro affinity for the (alpha4)2(beta2)3 and the alpha7* nAChR subtypes. Despite obvious structural similarities with the potent alkaloids pinnamine (5) and (-)-ferruginine (4) the pyranotropanes 6a and 6c exhibited distinctly lower nAChR affinities.

Animals↗
PubMed2002

[Contrast behaviour of a angiomyolipoma of the liver at echo-enhanced power-Doppler sonography].

Angiomyolipomas of the liver are rare tumours. Differentiation from other liver lesions using imaging techniques is difficult. This is the first report describing the contrast behaviour of an angiomyolipoma of the liver with echo-enhanced power-Doppler sonography. A rapid signal enhancement of the arteries within the tumour and an immediate drainage of the blood into the liver veins was demonstrated. Furthermore, spectrums similar to av-fistulas could be detected. Portal venous blood flow, irregular calibre of the vessels or chaotic vascular patterns could not be found.

Angiomyolipoma↗
PubMed2001

Photooxygenation of the helimers of (-)-isocolchicine: regio- and facial selectivity of the [4 + 2] cycloaddition with singlet oxygen and surprising endoperoxide transformations.

Photooxygenation of the helimeric mixture of (-)-(M,7S)/(P,7S)-isocolchicine (6) with the superdienophile singlet oxygen has been studied. Cycloaddition occurred with high regioselectivity at the 7a,11-positions of the alkaloid and predominantly at the diene face anti to the amidic substituent at the stereogenic center C-7, leading to two endoperoxides 7 (syn) and 8 (anti) with an 1:7 ratio. The structure of the minor product 7 was established by X-ray analysis. Investigation of the triethylamine induced transformation of the predominant endoperoxide 8 furnished a mixture of two isomers (M,7S)-10a/(M,7S)-10b in a 2:1 ratio possibly with constitutional interconversion and with (M,7S)-9 as plausible intermediate. Treatment of this mixture with silica gel/ethyl acetate at ambient temperature surprisingly led to an atropenantiomerically pure colchicinoid (M,7S)-12 characterized by an eightmembered oxocine B-ring, the structure and absolute configuration of which could be determined by X-ray analysis. For the unprecedented formation of the novel colchicinoid (M,7S)-12 a plausible reaction pathway is suggested, involving a complete transfer of the (M) helical asymmetry of the intermediate (M)-11 into (S) asymmetry of the newly formed carbon center of (M,7S)-12. Prerequisite for such a scenario is the configurational stability of the intermediate pseudobiaryl (M)-11, under the conditions employed, allowing to transmit the axial chirality onto the chiral center of the product (M,7S)-12.

Journal Article↗
PubMed2001

exo-2-(Pyridazin-4-yl)-7-azabicyclo[2.2.1]heptanes: syntheses and nicotinic acetylcholine receptor agonist activity of potent pyridazine analogues of (+/-)-epibatidine.

A new strategy for the straightforward synthesis of novel racemic epibatidine analogues is presented, in which the 2-chloropyridinyl moiety of epibatidine is bioisosterically replaced by differently substituted pyridazine rings. A key step of the new syntheses is the inverse type Diels-Alder reaction of the electron-rich enol ether 13 with the electron-deficient diazadiene systems of the 1,2,4, 5-tetrazines 14a-d to yield the novel pyridazine analogues of (+/-)-epibatidine 18, 19, 22, and 24. In addition preparation of the N-substituted derivatives, such as 26 and 28, is described. The structures of the novel epibatidine analogues were assigned on the basis of spectral data, that of compound 24 being additionally verified by X-ray crystallography exhibiting two racemic solid-state conformations in the crystal lattice and representing the first X-ray structure of an unprotected 7-azabicyclo[2.2.1]heptane moiety. The nAChR agonist activity of the racemic compounds 18, 19, 22, 24, and 28 was assayed in vitro by whole-cell current recordings from Xenopus oocytes expressing different recombinant nicotinic receptors from the rat. Among the compounds synthesized and tested, the pyridazine analogue 24 of (+/-)-epibatidine and its N-methyl derivative 28 were found to be the most active ones retaining much of the potency of natural epibatidine but with a substantially improved selectivity ratio between the alpha4beta2 and alpha3beta4 subtypes.

Animals↗
PubMed2001

[50 years of Barrett esophagus. Current diagnostic possibilities in pathology].

The most important differential diagnosis of specialized intestinal columnar cell metaplasia (Barrett's-mucosa) is the intestinal metaplasia of the cardia mucosa (possibly caused by Helicobacter infection). Furthermore it happens from time to time that Barrett's regenerative epithelium is overdiagnosed as low-grade dysplasia (unequivocal intraepithelial neoplasia). This might explain the disappearance of many low-grade dysplasias during further follow-up. Mucosal adenocarcinomas are often underdiagnosed as dysplastic lesions. Therefore many authors tried to establish molecular methods for improvement of the diagnostic possibilities. Immunohistochemistry or PCR with p53 and HER 2-neu might give at least some help but a negative reaction does not exclude a neoplasia in every case. The gold standard is careful endoscopy and biopsy taking with good documentation of the endoscopical findings and most important still the routine H&E stain are the only reliable diagnostic tools.

Adenocarcinoma↗
PubMed2001

Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands.

We have developed one-step syntheses of halogenated derivatives of (-)-cytisine featuring a halogen substituent at positions 3, 5 or 3 and 5 of the 2-pyridone fragment, and prepared the novel bioisosteric thiocytisine by oxygen-sulphur exchange. The affinities of these pyridone-modified analogs of (-)-cytisine for (alpha 4)(2)(beta 2)(3) and alpha 7* nAChRs in rat forebrain membranes were determined by competition with (+/-)-[(3)H]epibatidine and [(3)H]MLA, respectively. The 3-halocytisines 7 possess subnanomolar affinities for (alpha 4)(2)(beta 2)(3) nAChRs, higher than those found for (-)-cytisine as well as for the 5-halocytisines 8 and 3,5-dihalocytisines 6. In contrast to the parent alkaloid the 3-halogenated species display much a higher affinity for the alpha 7* nAChR subtype. The most potent molecule was 3-bromocytisine (7b) with preferential selectivity (200-fold) for the (alpha 4)(2)(beta 2)(3) subtype [K(i)=10 pM (alpha 4 beta 2) and 2.0 nM (alpha 7*)]. Replacement of the lactam with a thiolactam pharmacophore to thiocytisine (12) resulted in a subnanomolar affinity for the (alpha 4)(2)(beta 2)(3) nAChR subtype (K(i)=0.832 nM), but in a drastic decrease of affinity for the alpha 7* subtype; thiocytisine (12) has a K(i) value of 4000 nM (alpha 7*), giving a selectivity of 4800-fold for the neuronal (alpha 4)(2)(beta 2)(3)-nAChR and thus displaying the best affinity-selectivity profile in the series under consideration.

Aconitine↗