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S Schulz

Publications and source records attributed to S Schulz.

At least 37 records · Page 2Linked to original sources
PubMed2004

Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen.

We examined the effect of five anaesthetic drugs commonly used in laboratory animal research (tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane) on the expression of four pro-inflammatory cytokines. The anaesthetic agents were applied at dosages normally used for deep surgical anaesthesia. Semiquantitative image analysis of interleukin (IL)-1beta, IL-2, IL-6, and tumour necrosis factor alpha (TNFalpha) mRNA expression in the spleen of male Wistar rats 4 h after application of the anaesthetic drugs showed that these had moderate immunomodulatory effects. Ketamine/xylazine, chloral hydrate, and pentobarbital enhanced the basal expression of IL-1beta and IL-6 mRNA in rat spleen, while urethane reduced splenic IL-1beta mRNA expression. Tribromoethanol, ketamine/xylazine, and urethane reduced the basal TNFalpha mRNA levels, whereas TNFalpha mRNA expression was unaffected by chloral hydrate and by pentobarbital. The data demonstrate that these anaesthetics have slight, but significant, effects on the basal immune status of rats.

Adjuvants, Immunologic↗
PubMed2003

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism.

Defending cellular integrity against disturbances in intracellular concentrations of ATP ([ATP](i)) is predicated on coordinating the selection of substrates and their flux through metabolic pathways (metabolic signaling), ATP transfer from sites of production to utilization (energetic signaling), and the regulation of processes consuming energy (cell signaling). Whereas NO and its receptor, soluble guanylyl cyclase (sGC), are emerging as key mediators coordinating ATP supply and demand, mechanisms coupling this pathway with metabolic and energetic signaling remain undefined. Here, we demonstrate that sGC is a nucleotide sensor whose responsiveness to NO is regulated by [ATP](i). Indeed, ATP inhibits purified sGC with a K(i) predicting >60% inhibition of NO signaling in cells maintaining physiological [nucleotide](i). ATP inhibits sGC by interacting with a regulatory site that prefers ATP > GTP. Moreover, alterations in [ATP](i), by permeabilization and nucleotide clamping or inhibition of mitochondrial ATP synthase, regulate NO signaling by sGC. Thus, [ATP](i) serves as a "gain control" for NO signaling by sGC. At homeostatic [ATP](i), NO activation of sGC is repressed, whereas insults that reduce [ATP](i,) derepress sGC and amplify responses to NO. Hence, sGC forms a key synapse integrating metabolic, energetic, and cell signaling, wherein ATP is the transmitter, allosteric inhibition the coupling mechanism, and regulated accumulation of cGMP the response.

Adenosine Triphosphate↗
PubMed2003

The somatostatin sst2A receptor in the rat trigeminal ganglion.

Immunohistochemistry for the somatostatin sst2A receptor was performed on the rat trigeminal ganglion to know its function in the trigeminal nervous system. The immunoreactivity was detected in 9.4% of primary sensory neurons in the ganglion. These neurons were small to medium-sized (range=106.5-1123.2 microm(2); mean+/-S.D.=506.3+/-213.2 microm(2)) and predominantly located in the rostromedial part of the ophthalmo-maxillary division. They were also immunoreactive for calcitonin gene-related peptide and the vanilloid receptor subtype 1. In addition, 13.7% of trigeminal neurons which were retrogradely traced with fluorogold from the nasal mucosa exhibited sst2A receptor-immmunoreactivity. Trigeminal neurons which innervated the facial skin and tooth pulp were devoid of the immunoreactivity. In the brainstem trigeminal sensory nuclear complex, both the neuronal cell body and the neuropil exhibited sst2A receptor-immunoreactivity in the superficial medullary dorsal horn.The present study indicates that sst2A receptor-immunoreactive trigeminal nociceptors innervate the nasal mucosa. They may project to the superficial laminae of the medullary dorsal horn.

Animals↗
PubMed2003

Biochemical processing of plant acquired pyrrolizidine alkaloids by the neotropical leaf-beetle Platyphora boucardi.

Leaf beetles of the genus Platyphora, feeding on plant species containing pyrrolizidine alkaloids of the lycopsamine type, not only sequester these alkaloids and concentrate them in their exocrine defensive secretions, but also specifically process the plant acquired alkaloids. Using P. boucardi as subject, three mechanisms were studied: (i). utilization of host plant alkaloids that are not sequestered per se; (ii). elucidation of the mechanism of the already documented C-7 epimerization of heliotridine O(9)-monoesters; (iii). the specificity of insect catalyzed necine base esterification. P. boucardi does not sequester the triester parsonsine, the principal alkaloid of its host plant Prestonia portobellensis (Apocynaceae). Beetles fed with a purified mixture of nor-derivatives of parsonsine, obtained from Parsonsia laevigata, did not sequester the triesters but transformed them by partial degradation into monoesters that are accumulated in the defensive secretions. The mechanism of the previously described transformation of rinderine into intermedine by C-7 epimerization was elucidated by feeding C-7 deuterated heliotrine (3'-methylrinderine). The transformation of heliotrine into epiheliotrine (3'-methylintermedine) catalyzed by P. boucardi is accompanied by complete loss of deuterium, indicating the same mechanism of an oxidation-reduction process via a ketone intermediate as recently demonstrated in a pyrrolizidine alkaloid sequestering lepidopteran. P. boucardi is able to form ester alkaloids from five different necine bases fed as radioactively labeled substrates. However, besides C-7 epimerization the beetles are not able to convert simple necine bases into retronecine. The functional importance of the various alkaloid transformations is discussed in comparison to striking parallels of analogous reactions known from pyrrolizidine alkaloid sequestering Lepidoptera.

Animals↗
PubMed2003

Leptin-target neurones of the rat hypothalamus express somatostatin receptors.

Hypothalamic leptinoceptive neurones can be visualized by histochemical demonstration of leptin-induced nuclear translocation of the signalling molecule STAT3. We investigated the relationship of the leptinoceptive neurones to the somatostatin signalling system. With double-labelling immunohistochemistry, we studied the colocalization of leptin-activated transcription factor, STAT3, with somatostatin receptor subtypes, sst1, sst2A, sst2B, sst3 and sst4, or the neuropeptide itself, in the rat hypothalamus. Immunoreactivity for all the entities was widely distributed throughout the entire hypothalamus. Despite the wide distribution, only few cases of colocalization of somatostatin with leptin-activated STAT3 were detected in the paraventricular, arcuate and dorsomedial nuclei. A moderate to high degree of colocalization of nuclear STAT3 and all investigated subtypes of somatostatin receptors was found in the lateral and dorsal hypothalamic areas and in the dorsomedial hypothalamic nucleus. Immunoreactivity for sst1, sst2B and sst4 was present in STAT3-containing nuclei of the paraventricular, periventricular, arcuate and ventromedial hypothalamic neurones, as well as in the retrochiasmatic and posterior hypothalamic areas. Despite the wide distribution of sst2A in the rat hypothalamus, few events of colocalization with leptin-activated STAT3 were observed in the dorsomedial nucleus and in the lateral and dorsal hypothalamic areas only. Many leptin-responsive neurones of the dorsal, lateral, periarcuate, perifornical and posterior hypothalamic areas, as well as in the ventromedial and dorsomedial hypothalamic nuclei, displayed sst3 immunoreactivity at their neuronal cilia. These results provide strong anatomical evidence for the direct interaction of leptin and the somatostatin systems in neuroendocrine control loops such as the energy homeostasis, growth or stress response.

Animals↗
PubMed2003

Towards a broad-coverage biomedical ontology based on description logics.

We describe an ontology engineering methodology by which conceptual knowledge is extracted from an informal medical thesaurus (UMLS) and automatically converted into a formal description logics system (LOOM). Our approach consists of four steps: concept definitions are automatically generated from the UMLS, integrity checking of taxonomic and partonomic hierarchies is performed by LOOM's terminological classifier, cycles and inconsistencies are eliminated, as well as incremental refinement of the evolving knowledge base is performed by a domain expert. We report on experiments with a very large knowledge base composed of 164,000 concepts and 76,000 relations.

Artificial Intelligence↗
PubMed2003

Lymph node topography of the head and neck in New Zealand White rabbits.

Investigations of the lymphogenic metastatic spread of VX2 carcinomas in New Zealand White rabbits require an exact knowledge of the topography of cervical and facial lymph nodes. The topography of neck lymph nodes was evaluated from 16 rabbits macroscopically, histologically and by lymphographic investigations, and the possibility of their surgical removal (neck dissection) was examined. The upper aerodigestive tract and the ear of New Zealand White rabbits drain via four consistent groups of 12-18 lymph nodes. Except for the paratracheal lymph node, they are all easily accessible to surgery. The data presented in this study encourage the use of induced VX2 carcinomas in New Zealand White rabbits as an animal model to study the lymphogenic metastatic spread of squamous cell carcinomas of the head and neck. Such investigations could lead to an improvement of surgical and pharmaceutical treatment of this tumour entity.

Animals↗
PubMed2002

Somatostatin mediates nitric oxide production by activating sst(2) receptors in the rat retina.

Somatostatin and its receptors (ssts) are found in the retina. Recent evidence suggested the involvement of sst(2A) and sst(2B) receptors in the regulation of nitric oxide (NO) (). In this study, we investigated further the localization of sst(1), sst(3)-sst(5), and the possible involvement of all subtypes, present in the rat retina, in the regulation of NO production. Polyclonal antibodies raised against sst(1), sst(3-5) were applied to 10-14 micro m cryostat sections of rat retinas fixed in paraformaldehyde. NADPH-diaphorase reactivity was assessed histochemically. The levels of NO in rat retinal explants were assessed by the production of its stable metabolites NO(2)(-) and NO(3)(-). sst(1) immunofluorescence was detected mainly in the retinal pigment epithelium, blood vessels of the inner retina, where it was colocalized with NADPH-diaphorase, and in processes of the inner plexiform layer (IPL). sst(4) immunohistochemistry was found in ganglion cell bodies, where it was colocalized with NADPH-diaphorase, processes of the IPL and ganglion cell layer, and optic nerve fibers. sst(3) or sst(5) immunostain was not detected. Somatostatin increased NO production and this effect was mimicked only by the sst(2) specific analog L-779976. The sst(2) antagonist CYN-154806 blocked the L-779976 increase of NO production. These results present conclusive evidence that somatostatin's role in the retina involves the regulation of NO by an sst(2) mechanism.

Animals↗
PubMed2002

[Acute ischemia of the leg in a drug addict].

A 39 year old male comes to the emergency room because of rapidly increasing pain in his left leg one hour after the injection of Flunitrazepam into a groin vessel. There is a history of drug abuse for more than 15 years. The left leg is cool and shows intense patchy cyanosis. The same skin discoloration is seen at the left lower abdomen and parts of the thigh. The leg is paretic but foot-pulses are detectable. Color-coded duplex-sonography of the left leg shows normal shaped arteries with regular flow. Regarding the veins there are post-thrombotic changes but no signs of actual thrombosis. The ECG shows sinus rythme. No source of emboli can be found by echocardiography. The laboratory tests reveal normal results except of anemia (Hb 9.6 g/dl, normocytic, normochromic). As an accidental intraarterial injection with a toxic/allergic insult to the vessel-walls has to be supposed the patient is treated besides of analgesics with systemic anticoagulation, high doses of cortisone and calcium channel-blockers. With this therapeutic regimen the leg and the left lower abdomen improve gradually except for some toes which remain cyanotic. During the first days the patient develops signs of moderate rhabdomyolysis with swelling of the leg and an increase of creatininase concentration in blood. After 12 days the left leg has normalised but the toes show further demarcation. They have to be amputated six weeks later. The accidental injection of drugs into the femoral artery may result in the clinical picture of acute limb ischemia without occlusion of the big vessels of the leg. This obviously occurs most often with benzodiazepines, especially when crushed tablets soluted in water are injected. Color-coded duplex sonography is able to show open vessels within minutes and prevents ineffective surgical interventions.

Adult↗
PubMed2002

Color coded duplex sonography of inguinal vessels in i.v. drug addicts.

BACKGROUND: During recent years increasing numbers of intravenous drug addicts with severe damage to the groin vessels were examined in our angiological ultrasound laboratory. The value of color duplex sonography for the clinical evaluation of these findings is the subject of the present study. PATIENTS AND METHODS: Over the course of six years every drug addict admitted to our hospital who either complained of pain or discomfort in the inguinal region or showed conspicuous clinical findings in this area was examined in our ultrasound laboratory. First by B-mode, the diameter, wall structure and compressibility of the vessels were evaluated and the surrounding tissue was checked for abnormalities. Then the blood flow of the femoral vessels was examined by color coded duplex. If an abscess was suspected, a computed tomography of the groin was obtained before surgery in most cases. RESULTS: A total number of 77 patients was examined with pathologic results in all cases. The most frequent finding was venous thrombosis: In 63 patients complete thrombotic occlusion of the femoral vein at the injection site was observed. We registered 14 partial thromboses. 30 patients showed vessel wall alterations to variable extents in which 23 cases referred to veins and 10 cases to arteries. 7 patients showed an occlusion of the femoral artery. In 4 patients we found a false aneurysm and 3 had an arteriovenous fistula. Chronic tissue alterations were present to a certain extent in all cases rendering evaluation frequently difficult. Especially problematic to evaluation were those 34 patients where one or more surgical interventions had been performed previously. The results of an additional computed tomography had little effect on the therapeutic decisions. In 11 patients an abscess incision had to be done during the course of their hospital stay. CONCLUSION: Extensive damage of the groin vessels is seen in i.v. drug addicts. There is no other patient group with such a diversity of different findings. In almost every case these findings involve veins and arteries as well as the surrounding tissues.

Abscess↗
PubMed2002

Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies.

BACKGROUND AND AIMS: Recently, novel somatostatin receptor (sstr) subtype specific ligand analogues have been developed for medical treatment of neuroendocrine tumours expressing different sstrs (sstr1-5). At present, individual expression patterns of sstr subtypes are based on methods such as in situ hybridisation and polymerase chain reaction at the transcriptional level. Therefore, we generated subtype specific antibodies against sstr1, 2A, 3, and 5 and analysed their presence, cellular localisation, distribution, and expression pattern in 33 gastrinomas, 36 insulinomas, and 35 tumours associated with a carcinoid syndrome by immunohistochemistry at the translational level. METHODS: Western blotting experiments were performed in the normal human pancreas used as a reference organ and in tumour tissues; at the cellular level, sstrs were localised by immunohistochemistry in tissue paraffin sections. RESULTS: In western blot analyses, the antibodies identified the respective receptors in their correct molecular range in extracts of the pancreas and neuroendocrine tumours. Using immunohistochemistry and immunofluorescence, the antibodies specifically detected the receptors in islet cells of the normal pancreas. Immunohistochemistry in the tumours revealed that all investigated sstr subtypes were highly expressed in the different tumour types. The frequency and expression pattern of the individual sstr subtypes varied considerably not only between the different tumour types but also in each patient. CONCLUSIONS: We conclude that immunohistochemistry with subtype specific antibodies can be used in clinical routine work to analyse sstr expression patterns for each patient before treatment and to facilitate well directed individual medical therapy by administering subtype specific somatostatin analogues.

Antibody Specificity↗
PubMed2002

[Expanding control possibilities of myoelectric hand prostheses].

Raising control possibilities of myoelectric prostheses--The control of hand prostheses is based on the surface scan of myoelectric voltage caused by muscle contractions in an amputees arm stump. So far available prostheses only perform up to two different grip types. This paper introduces a control scheme that is able to execute a variety of grip types dependent on the patient's control signals. Therefore a platform is presented to adapt control parameters especially to the patients anatomy. Developed algorithms are flashed on a microcontroller, processing data online and controlling a new generation of prostheses (FZK-prosthesis, Forschungszentrum Karlsruhe).

Amputation Stumps↗
PubMed2001

Nucleotide requirements for CDX2 binding to the cis promoter element mediating intestine-specific expression of guanylyl cyclase C.

Guanylyl cyclase C (GC-C), specifically expressed by intestinal epithelial cells, is the receptor for the Escherichia coli heat-stable enterotoxin that causes diarrhea. Tissue-specific expression of GC-C is mediated by the intestinal transcriptional regulator CDX2. This trans-activating protein regulates intestine-specific expression by binding to a critical sequence in the proximal promoter of GC-C. The precise nucleotide elements mediating CDX2 binding to promoter elements remain undefined. Several nuclear proteins form complexes with a DNA probe containing the promoter element of GC-C mediating CDX2 binding. The present study examined the nucleotide requirements in the consensus binding site and flanking regions in the cis element that mediates specific CDX2 binding to the promoter of GC-C. These studies identified seven core base pairs in the critical promoter element mediating tissue-specific expression of GC-C that are required for CDX2 binding. In addition, base pairs flanking this core sequence contribute to and are required for CDX2 recognition. These studies describe the precise nucleotide sequence within the GC-C promoter that comprises the CDX2 binding site required for intestine-specific expression.

3' Flanking Region↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗