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Biomedical subjects

S Schulz

Publications and source records attributed to S Schulz.

At least 19 recordsLinked to original sources

Ectopic expression of guanylyl cyclase C in CD34+ progenitor cells in peripheral blood.

PURPOSE: To examine the utility of guanylyl cyclase C (GC-C)-specific nested reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating tumor cells in patients with colorectal cancer. PATIENTS AND METHODS: Peripheral-blood mononuclear cells from 24 patients with Dukes' stage D colorectal cancer were analyzed by GC-C-specific nested RT-PCR using 1 microg of total RNA. Peripheral-blood mononuclear cells from 20 healthy volunteers served as controls. Additionally, peripheral-blood CD34+ progenitor cells were assayed for the expression of both GC-C and other epithelial cell-specific markers. RESULTS: GC-C mRNA was detected in blood mononuclear cells from all 24 patients with colorectal cancer and all healthy volunteers. These unexpected positive results reflected low-level ectopic transcription of GC-C in CD34+ progenitor cells. Moreover, CD34+ progenitor cells expressed other epithelial cell-specific markers, including prostate-specific antigen, prostate-specific membrane antigen, carcinoembryonic antigen, CK-19, CK-20, mucin 1, and GA733.2. Limiting the quantity of mononuclear cell total RNA analyzed to < or = 0.8 microg eliminated detection of GC-C and other tissue-specific transcripts in blood of healthy volunteers. However, under the same conditions, GC-C mRNA was detected in mononuclear cells from all 24 patients with metastatic colorectal cancer. Using 0.5 microg of total RNA and GC-C-specific primers, nested RT-PCR detected a single human colon carcinoma cell (approximately 20 to 200 GC-C transcripts/cell) in 10(6) to 10(7) mononuclear blood cells. CONCLUSION: These data suggest that GC-C may be useful for detecting circulating colorectal cancer cells. They also demonstrate that CD34+ cells are a source of ectopically expressed epithelial cell-specific markers and that CD34+ cells may contribute to the high false-positive rate generally observed when those markers are used to detect rare circulating metastatic cancer cells by RT-PCR.

Adult↗

Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma cells.

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, assessed by trypan blue exclusion and lactate dehydrogenase release. Rather, ST prolonged the cell cycle, assessed by flow cytometry and [(3)H]thymidine incorporation into DNA. The cytostatic effects of GC-C agonists were associated with accumulation of intracellular cGMP, mimicked by the cell-permeant analog 8-Br-cGMP, and reproduced and potentiated by the cGMP-specific phosphodiesterase inhibitor zaprinast but not the inactive ST analog TJU 1-103. Thus, GC-C agonists regulate the proliferation of intestinal cells through cGMP-dependent mechanisms by delaying progression of the cell cycle. These data suggest that endogenous agonists of GC-C, such as uroguanylin, may play a role in regulating the balance between epithelial proliferation and differentiation in normal intestinal physiology. Therefore, GC-C ligands may be novel therapeutic agents for the treatment of patients with colorectal cancer.

Bacterial Toxins↗

C-terminal splice variants of the mouse mu-opioid receptor differ in morphine-induced internalization and receptor resensitization.

The main analgesic effects of the opioid alkaloid morphine are mediated by the mu-opioid receptor. In contrast to endogenous opioid peptides, morphine activates the mu-opioid receptor without causing its rapid endocytosis. Recently, three novel C-terminal splice variants (MOR1C, MOR1D, and MOR1E) of the mouse mu-opioid receptor (MOR1) have been identified. In the present study, we show that these receptors differ substantially in their agonist-selective membrane trafficking. MOR1 and MOR1C stably expressed in human embryonic kidney 293 cells exhibited phosphorylation, internalization, and down-regulation in the presence of the opioid peptide [d-Ala(2),Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO) but not in response to morphine. In contrast, MOR1D and MOR1E exhibited robust phosphorylation, internalization, and down-regulation in response to both DAMGO and morphine. DAMGO elicited a similar desensitization (during an 8-h exposure) and resensitization (during a 50-min drug-free interval) of all four mu-receptor splice variants. After morphine treatment, however, MOR1 and MOR1C showed a faster desensitization and no resensitization as compared with MOR1D and MOR1E. These results strongly reinforce the hypothesis that receptor phosphorylation and internalization are required for opioid receptor reactivation thus counteracting agonist-induced desensitization. Our findings also suggest a mechanism by which cell- and tissue-specific C-terminal splicing of the mu-opioid receptor may significantly modulate the development of tolerance to the various effects of morphine.

Alternative Splicing↗

Long-term colony housing in Long Evans rats: immunological, hormonal, and behavioral consequences.

The distribution pattern and the function of blood immune cells were investigated for 10 weeks in three mixed-sex colonies of Long Evans rats. After colony formation, a despotic dominance system was established between the males. This paper focuses on differences between subdominant colony and pair-housed control males. A reduced body mass development and hormonal status in subdominant males indicate stressful colony conditions. Subdominant males had lower numbers of CD4 and CD8 T cells, pronounced granulocytosis and reduced lymphocyte proliferation rates as compared with controls. The persistency of changes in subdominant males offers the opportunity to investigate the effects of long-term immuno-modulation on health.

Animals↗

Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice.

Mice lacking D1 receptors were used to study the role of these receptors in morphine-induced antinociception and locomotor sensitisation. In the hot-plate test D1 receptor deficient (-/-) and wild-type (+/+) mice showed similar reaction times under basal conditions. A single injection of 1.25 mg/kg and 2.5 mg/kg morphine resulted in a stronger antinociceptive response in D1 receptor deficient mice than in wild-type animals. Tolerance to the analgesic effect did not develop in both groups of animals when 12.5 mg/kg morphine was chronically applied twice daily for 13 days. There was no change in basal locomotor activity between saline-injected wild-type and D1 receptor deficient mice. After chronic treatment wild-type mice showed a continuous increase in locomotor activity, indicating the development of sensitisation. In contrast, a subchronic administration of morphine did not change locomotor activity in mutant mice. The lack of the development of locomotor sensitisation in D1 deficient mice was associated with reduced levels of immunoreactive mu opioid receptors in dorsal striatal patches as compared to wild-type mice. In contrast, no change in the distribution of immunoreactive mu receptors could be detected in areas related to pain pathways such as the spinal cord. Taken together, these results suggest an involvement of D1 receptors in morphine-induced locomotor activity and analgesia.

Analgesics, Opioid↗

Female sex pheromone of a wandering spider (Cupiennius salei): identification and sensory reception.

Females of the wandering spider Cupiennius salei attach a sex pheromone to their dragline. Males encountering the female dragline examine the silk thread with their pedipalps and then typically initiate reciprocal vibratory courtship with the sexual partner. The female pheromone was identified as (S)-1,1'-dimethyl citrate. The male pheromone receptive sensory cells are located in tip pore sensilla and respond to touching the sensillum tip with female silk or pieces of filter paper containing the synthetic pheromone.

Animal Communication↗

Composition of the silk lipids of the spider Nephila clavipes.

A detailed analysis of the lipids of spider silk is given for the first time. Extracts of the silk from the golden orb weaver, Nephila clavipes, were studied by gas chromatography, mass spectrometry, and chemical derivatizations. The major group of the lipids consisted of methyl-branched 1-methoxyalkanes (methyl ethers) with up to four methyl groups in the chain (chain length between C28 and C34), which are unique to spiders. The position of the methyl branches was determined by conversion into cyanides, which allowed easy location of methyl branches. The second-largest group included alkanes with a wide structural variety; 2-methyl-branched, even-numbered hydrocarbons predominated. A general numerical method for the estimation of retention indices of alkanes and their derivatives is presented. Further components of the web included alkanols and alkanediols, fatty acids, and glyceryl ethers. Some comments on the biosynthesis of these compounds are also given.

Alcohols↗

Analysis of volatiles induced by oviposition of elm leaf beetle Xanthogaleruca luteola on Ulmus minor.

Egg deposition of the elm leaf beetle Xanthogaleruca luteola causes the emission of volatiles from its food plant, Ulmus minor. These volatiles are exploited by the egg parasitoid, Oomyzus gallerucae, to locate its host. In contrast to other tritrophic systems, the release of volatiles is not induced by feeding but by egg deposition. Previous investigations showed that the release is systemic and can be triggered by jasmonic acid. Comparison of headspace analysis revealed similarities in the blend of volatiles emitted following egg deposition and feeding. The mixture consists of more than 40 compounds; most of the substances are terpenoids. Leaves next to those carrying eggs emit fewer compounds. When treated with jasmonic acid, leaves emit a blend that consists almost exclusively of terpenoids. Dichloromethane extracts of leaves treated with jasmonic acid were also investigated. After separation of extracts of jasmonate induced elm leaves on silica, we obtained a fraction of terpenoid hydrocarbons that was attractive to the parasitoids. This indicates that jasmonic acid stimulates the production of terpenoid hydrocarbons that convey information of egg deposition to the parasitoid.

Animals↗

Biclonality of gastric lymphomas.

The pathogenesis and clonal evolution of gastric diffuse large B-cell lymphoma (DLBCL) and its relationship to extranodal marginal zone B-cell lymphoma (MZBL), mucosa-associated lymphoid tissue (MALT) type, are still controversial. The aim of this study was to establish the clonality of morphologically distinct areas of gastric lymphomas as well as their genetic relationship to each other. Six gastric lymphomas, consisting of two MZBL, MALT type, two DLBCL, and two "composite" lymphomas were subjected to laser capture microdissection and subsequent PCR-based amplification of the immunoglobulin heavy chain gene. One DLBCL showed a biclonal pattern of rearranged immunoglobulin heavy chain (IgH) genes of two different areas without evidence of a common origin. Two composite DLBCL with areas of extranodal MZBL, MALT type, were also biclonal and displayed different IgH gene rearrangements in the small-cell and in the large-cell components, respectively. Sequencing of the CDR3 region revealed unique VH-N-D and D-N-JH junctions, thus corroborating the presence of two genuinely distinct tumor clones in each of these three cases. In contrast, the remaining three gastric lymphomas (one DLBCL and two MZBL, MALT type) showed IgH gene rearrangements in which CDR3 regions were identical in the different tumor areas. Our results suggest that gastric DLBCL may be composed of more than one tumor cell clone. Further, DLBCL may not necessarily evolve by transformation of a low-grade lymphoma, but may also originate de novo. An ongoing emergence of new tumor clones may considerably hamper molecular diagnosis and follow-up of gastric DLBCL.

Base Sequence↗

Pain management in children: assessment and documentation in burn units.

Burns are considered to be among the most painful types of trauma. Especially the pain of children is often unsatisfactorily treated. This study investigates the assessment and documentation of pain by physicians and nurses in children suffering from burns. Pain management was considered sufficient in 80% of ventilated patients and in 60% of non-ventilated patients. The minority of the staff regarded pain management as sufficient during dressing changes after the acute phase and during nursing care. Thirty-eight per cent of the physicians and 58% of the nurses documented the pain. Standardized documentation was used by fewer than 20% of the staff. Pain documentation was not considered relevant for further therapy by 48% of the physicians. More than half of all participants believed that an improvement of the pain therapy performed in their hospital was necessary. Standardized documentation, an algorithm for the application of analgesics, and more training in pain management were desired by many staff members.

Burn Units↗

[Virtual conferences in medicine].

The Internet and high-speed communication facilities have tremendously simplified the exchange of multimedia data. E-mail and World Wide Web have become important tools for everyday information and communication. In recent years there have been numerous attempts to exploit web technology for virtual conferences. However, in the medical domain, only few virtual conferences could be established. We describe the architecture and typical features of virtual conferences, their organizational and technical requirements and discuss prerequisites for their successful implementation.

Computer Systems↗

Molecular diagnosis of a Mycobacterium chelonae infection.

A 23-year-old female presented with enlarged cervical lymph nodes, and a diagnosis of nonspecific lymphadenitis with formation of pyogranulomas was rendered. Despite an initial oral antibiosis and subsequent long-term intravenous and oral antibiosis under hospitalized conditions, the symptoms progressed. The lymph nodes became larger and then affected the cervical region bilaterally. Her general condition worsened, and an exanthema of the extremities accompanied by a reactive arthritis occurred. Serological assays of various viral and bacterial markers and blood cultures were negative. Application of a polymerase chain reaction (PCR) protocol allowing specific amplification of mycobacterial DNA revealed DNA of Mycobacterium chelonea in formalin-fixed, paraffin-embedded lymph node tissue. Sequencing of the PCR product showed a 97% homology with the known Mycobacterium chelonae sequence. Modification of the antibiotic therapy with clarithromycin, imipenem and amikacin resulted in a rapid regression of the symptoms. The clinical course, in combination with the difficulties in detecting the infectious agent, supports the usefulness of molecular pathological analyses specific for nontuberculous mycobacteria (NTM).

Adult↗

Carney complex--an unexpected finding during puerperium.

Carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with Carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing's syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of Obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L(2)/L(3) with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing's syndrome, it was recognized that the patient met the diagnostic criteria for Carney complex.

Acromegaly↗

[Genetic studies in the Cologne administrative district (North Rhine-Westphalia, Germany): DNA-STR systems FGA, TH01, VWA and YNZ22].

The DNA-STR systems FGA, TH01, VWA, YNZ22 have been studied in two German population samples (Eschweiler, Stolberg and Hürtgenwald, Inden, Langerwehe, administrative area of Cologne, Northrhine-Westphalia). The cluster analysis, including data from Düsseldorf, Germany and from Poland, resulted in a cluster with Eschweiler, Stolberg and Düsseldorf, separating to a certain degree Hürtgenwald, Inden, Langerwehe and Poland more clearly. In contrary to the expectations (based on the history of the migration from Northeastern Europe to Northrhine-Westfalia) and the results of the study of 22 hemogenetic systems (Scheil & Huckenbeck 2000) there was a somewhat larger genetic distance between Eschweiler, Stolberg and Poland than between Hürtgenwald, Inden, Langerwehe and Poland. The combined data of the four STRs and the 22 hemogenetic systems resulted--as expected--in smaller genetic distances between Eschweiler, Stolberg and Poland as well as between Düsseldorf and Poland. These different genetic distances are interpreted as a result of the migration from North-East Europe to North Rhine-Westphalia in the last 130 years and the selective geographic distribution of the migrants in the industrial and urbanised areas.

Alleles↗

Indexing medical WWW documents by morphemes.

Assisting users to search medical information on the WWW is here considered from two perspectives--the linguistic complexity of medical terms, nominal compounds in particular, and cross-lingual relationships between monolingual medical terminologies. In order to solve the first problem, we present an approach to automatic indexing in which medically plausible morphological units are used. Semantic value is added to these index terms by a compact domain-specific thesaurus. We further discuss tools for morphological segmentation and morphosemantic normalization of HTML documents, as well as an adaptation of a standard WWW search engine for morpheme-based retrieval. The second problem, cross-lingual medical document retrieval, is dealt with by defining cross-lingual equivalence relations on the emerging morpheme sets.

Abstracting and Indexing↗

Health informatics world wide--a WWW service for the health informatics community.

Health Informatics World Wide, a Web index of research and educational institutions in the fields of Health Informatics and Medical Informatics has been available to WWW users since 1995. In this paper we report on the original conception of this service, its subsequent modifications and address its maintenance and related problems. Access statistics are presented which demonstrate its relevance as well as the geographical focus of Health Informatics research and development.

Abstracting and Indexing↗