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Biomedical subjects

E Seifert

Publications and source records attributed to E Seifert.

At least 19 recordsLinked to original sources

Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.

The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.

Animals

Long-term results of treatment of malignant non-Hodgkin's lymphoma of the stomach.

Our experience with 66 endoscopic-bioptic diagnosed malignant non-Hodgkin's lymphomas (NHL) showed that in most of them (57 of 66 patients) a tumor stage IE or IIE was present. All 57 primary gastric lymphomas were B-cell-lymphomas arising from the mucosa-associated lymphoid tissue (MALT). After curative primary gastric resection in stage IE and IIE the 5-year survival rate was 81%, and the 5-years lymphoma-related survival rate was 88%. These results are superior to those reported in the literature. The following two points are probably of importance for improving the prognosis: early diagnosis made possible by better knowledge of the infiltrative-flat type of tumor growth (38 out of 57 patients, including 23 cases in which infiltration was limited to mucosa and submucosa = "early lymphoma"), and extensive preoperative staging. The infiltrative-flat type, which is difficult to diagnose endoscopically, usually shows low-grade malignancy on histology (76%; in early lymphoma 83%) and has an excellent prognosis when submitted to surgery. In our experience the question as to whether additional treatment by chemotherapy and/or radiotherapy improves the prognosis of NHL of the stomach remains unanswered and further studies are needed.

Combined Modality Therapy

[Evaluating the effectiveness of chemotherapy in patients with head-neck tumors using positron emission tomography (PET scan)].

Positron emission tomography (PET) demonstrates the qualitative and quantitative characteristics of multiple metabolic pathways. In a prospective study we evaluated the metabolism of glucose in the tumors of ten patients suffering from head and neck cancer before and after chemotherapy with cisplatin and 5-fluorouracil. Using 18-fluorodeoxyglucose (FDG), it was possible to show changes in tumor metabolism after chemotherapy. In general, chemotherapy reduced the volume of the primary tumor and the lymph nodes. There was a linear relation between the changes in metabolism and growth rate, but in a few patients the lymph nodes and the primary tumor showed a different metabolic reaction. With FDG metabolism and PET we were able to determine the response rate of the tumor in vivo before chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

[Exercise and sports therapy for patients with head and neck tumors].

Important aspects in the aftercare of patients with cancer of head and neck can be realized by physical training in a sports group. The aftermath of operative therapy, e.g. loss of motion, imbalances of muscular activity or respiratory movements, can be reduced. The main importance of physical training in a group is the patient's reintegration in a social environment. Evaluating the quality of life of the individual patient we found that this method of psychosocial aftercare can improve subjective quality of life. Therefore, this conception of rehabilitation should not be missing in the aftercare of patients with malignant cancer.

Combined Modality Therapy

Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study.

In a retrospective study (1982-1990), 12 adenomas, 35 carcinomas of the papilla of Vater, and 21 duodenal adenomas were examined. All patients had endoscopicbioptic examinations (5-10 forceps biopsies, snare biopsy or forceps-biopsies after endoscopic sphincterotomy). Special attention was paid to malignant transformation of adenomas and of residual adenomatous tissue in surgical resected cancer. Follow-up data were gained by reexamination or questionnaires. In papillary adenomas, an adenocarcinoma was found in 30% at operation or by follow-up. In 41.2% of the operated cases, residual adenomatous tissue was found, more often in well-differentiated adenocarcinomas than in other histological types. A transformation from duodenal adenomas to adenocarcinomas was seen less frequently (9.5%). Therefore, the risk of malignancy in ampullary adenomas is greater than elsewhere in the duodenum. In eight of 11 patients (72.7%) with duodenal adenomas, one or more simultaneously developed colonic adenomas were found (in four cases a Gardner syndrome not known before). We conclude that there is strong evidence that most ampullary and duodenal carcinomas develop in preexisting adenomas, with an adenoma-cancer sequence similar to that accepted for colorectal carcinoma. This has to be kept in mind for diagnostic as well as therapeutic reasons. When either an adenoma of the ampulla or duodenum is diagnosed, colonoscopy is mandatory to find or exclude colonic adenomas. In patients with familiar adenomatosis, the duodenum and the papilla of Vater have to be examined endoscopically.

Adenocarcinoma

Gene expression mediated by cis-acting sequences of the Krüppel gene in response to the Drosophila morphogens bicoid and hunchback.

The initial expression of the gap gene Krüppel (Kr) occurs in a precisely bounded central region of the Drosophila blastoderm embryo. According to genetic analysis, the spatial limits of the Kr expression domain are controlled by the morphogenetic activities of the anterior organizer gene bicoid (bcd) and the anterior gap gene hunchback (hb). Using gene fusion analysis, we assayed for cis-acting sequences of the Kr gene which mediate transcriptional activation and localized gene expression in response to trans-acting factors. A 730 bp Kr control element drives gene expression in place of the endogenous Kr central domain. This cis-acting element, Kr730, is composed of bcd and hb responsive sequences. They map into regions of multiple hb and bcd protein in vitro binding sites. A 142 bp core fragment containing one low affinity hb and five medium to strong bcd protein binding sites drives gene expression in a Kr-like location in the centre of the embryo. Our results show that this fragment represents a target for the redundant activator/repressor system provided by the anterior morphogens bcd and hb.

Animals

[Risks of a cartilage-bone bank with reference to HIV infection].

Allogenic transplants have an established place in reconstructive procedures. For years it has been suspected that lyophilized dura mater can transmit Creutzfeld-Jakob disease. HIV infection with fully manifest AIDS and a mortality of up to 100% is now also increasing in significance. It is necessary to assess the risk of transferring HIV with allogenic transplants because HIV passes into the cell via specific surface receptors and is integrated within the chromosome. Experimental data on disinfection and sterilization of allogenic transplants stored within chromosomes and their inactivation are not available. Allogenic transplants are only used in operations for life-threatening disease. As a rule, these are elective operations which must meet the highest safety standards, also with regard to the danger of infection. Collaboration with a transplantation team is essential.

Bone Transplantation

Gradients of Krüppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo.

Abdominal segmentation of the Drosophila embryo requires the activities of the gap genes Krüppel (Kr), knirps (kni), and tailless (tll). They control the expression of the pair-rule gene hairy (h) by activating or repressing independent cis-acting units that generate individual stripes. Kr activates stripe 5 and represses stripe 6, kni activates stripe 6 and represses stripe 7, and tll activates stripe 7. Kr and kni proteins bind strongly to h control units that generate stripes in areas of low concentration of the respective gap gene products and weakly to those that generate stripes in areas of high gap gene expression. These results indicate that Kr and kni proteins form overlapping concentration gradients that generate the periodic pair-rule expression pattern.

Animals

cis-acting control elements for Krüppel expression in the Drosophila embryo.

Krüppel (Kr), a gap gene of Drosophila, shows complex spatial patterns of expression during the different stages of embryogenesis. In order to identify cis-acting sequences required for normal Kr gene expression, we analysed the expression patterns of fusion gene constructs in transgenic embryos. In these constructs, bacterial lacZ expression was placed under the control of Kr sequences in front of a basal promoter. We identified cis-acting Kr control units which drive beta-galactosidase expression in 10 known locations of Kr expression in early and late embryos. More than one cis-regulatory element drives the expression in the anterior domain at the blastoderm stage, in the nervous system, the midline precursor cells and in the amino-serosa. In addition, two cis-acting elements direct the first zygotic expression of Kr in a striped subpattern within the central region of the blastoderm embryo. Both elements respond to alterations in the activities of maternal organizer genes known to be required for Kr expression in establishing the thoracic and anterior abdominal segments in the wild-type embryo.

Animals

Regulatory elements controlling expression of the Drosophila homeotic gene fork head.

The region-specific homeotic gene fork head (fkh) is expressed and required in a variety of tissues of the developing Drosophila embryo. In order to identify the cis regulatory elements directing the complex spatio-temporal expression pattern of fkh, we have studied the subpatterns directed by defined fragments of fkh genomic DNA. These experiments enabled us to distinguish separate regulatory elements specific for the different expression domains of fkh. In addition, our analysis revealed several unexpected features such as the redundancy of regulatory elements and the overlap of regulatory elements with the transcribed regions of other genes. Moreover, the separation of normally contiguous elements effecting expression in the posterior terminal fkh domain appears to lead to novel expression domains which do not correspond to known developmental units in the embryo.

Alleles

[Reduction of reactivity to allergic rhinitis with intravenous administration of calcium. Clinical-experimental study on the effect of changes of local airway resistance after nasal allergen provocation].

The antiallergic activity of calcium was investigated in 25 patients with allergic rhinitis by nasal provocation with increasing doses of phleum pratense during a symptom free interval. Prior to that provocation, the patients received 9 mmol calcium (Calcium-Sandoz) i.v. or placebo respectively (double blind cross-over design). The concentration of serum calcium increased after calcium injection by 0.45 +/- 0.055 mmol/l. Calcium exerted a significant protective effect as compared to placebo: higher allergen doses, (p = 0.021) i.e. 20433 biological units/ml vs. 7494 biological units/ml, were required in order to induce a defined allergic reaction (50% decrease of nasal air flow). The data thus furnish evidence that intravenous calcium reduces the allergic response in type I allergy.

Adult

Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo.

Segmental pattern formation in Drosophila proceeds in a hierarchical manner whereby the embryo is stepwise divided into progressively finer regions until it reaches its final metameric form. Maternal genes initiate this process by imparting on the egg a distinct antero-posterior polarity and by directing from the two polar centres the activities of the zygotic genes. The anterior system is strictly dependent on the product of the maternal gene bicoid (bcd), without which all pattern elements in the anterior region of the embryo fail to develop. The posterior system seems to lack such a morphogen. Rather, the known posterior maternal determinants simply define the boundaries within which abdominal segmentation can occur, and the process that actively generates the abdominal body pattern may be entirely due to the interactions between the zygotic genes. The most likely candidates among the zygotic genes that could fulfil the role of initiating the posterior pattern-forming process are the gap genes, as they are the first segmentation genes to be expressed in the embryo. Here we describe the interactions between the gap genes Krüppel (Kr), knirps (kni) and tailless (tll). We show that kni expression is repressed by tll activity, whereas it is directly enhanced by Kr activity. Thus, Kr activity is present throughout the domain of kni expression and forms a long-range protein gradient, which in combination with kni activity is required for abdominal segmentation of the embryo.

Animals

The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo.

The region-specific homeotic gene fork head (fkh) promotes terminal as opposed to segmental development in the Drosophila embryo. We have cloned the fkh region by chromosomal walking. P element-mediated germ-line transformation and sequence comparison of wild-type and mutant alleles identify the fkh gene within the cloned region. fkh is expressed in the early embryo in the two terminal domains that are homeotically transformed in fkh mutant embryos. The nuclear localization of the fkh protein suggests that fkh regulates the transcription of other, subordinate, genes. The fkh gene product, however, does not contain a known protein motif, such as the homeodomain or the zinc fingers, nor is it similar in sequence to any other known protein.

Alleles

[Pattern formation in Drosophila].

Drosophila proved an excellent system to study molecular processes in establishing the body pattern of an embryo. Genes which are active during oogenesis provide localized cues which regulate a cascade of zygotic genes that determines the developmental fate of the blastoderm cells along the longitudinal axis of the embryo.

Animals

[Assessment of the quality of life of patients with incurable head-neck tumors].

Assessment of the quality of life is an additional, perhaps crucial criterion for deciding on the choice of a palliative therapy. Therefore it is necessary to know what "quality of life" means to the individual patient. We developed a questionnaire in cooperation with patients suffering from cancer of head and neck. With this questionnaire it is possible to judge how the patient rates his own quality of life. The questionnaire helps the physician to develop a palliative therapy schedule taking the psyosocial background into consideration. It improves the practicability of prospective studies concerning palliative therapy schedules.

Activities of Daily Living

[Quo vadis endoscopic sphincterotomy?].

The results of a study from 25 centers (= Series I: 1974-1980) covering 9041 endoscopic sphincterotomies (EST) were compared with those of a second study from 20 centers (= Series II: 1981-1986) covering 10177 cases. A change was seen in the indications during the past 5 years: While choledocholithiasis after cholecystectomy remained the main indication, EST is performed with increasing frequency in patients with common bile duct stones having their gallbladder in situ as a definitive method with low complications (only 0.61% emergency cholecystectomies): Circumscript papillary stenosis became quite a rare indication. The success rate of EST because of choledocholithiasis was not improved in spite of new techniques (stone-free common bile ducts in I: 84.06%, in II: 83.97%). The complication rate decreased from 7.55% to 5.04%. Types of complications did not change. Only perforations decreased, the rates of bleeding, cholangitis and pancreatitis remained the same. The mortality diminished from 1.12% to 0.60% (the figures remained twice as high in papillary stenosis than in choledocholithiasis). There was no change in the results of EST during the past 5 years. Follow-up studies using radiological methods show worse results (recurrent stones in II: 21.2%, in I: 5.8%, stenosis of EST in II: 6.1%, in I: 3.1%): Late results of EST because of papillary stenosis are still worse compared to those of choledocholithiasis. Therefore, in spite of increasing experience and introduction of new techniques the method became safer, but the therapeutic results did not appreciably improve.

Ampulla of Vater