PubMed Health⌕ Search

Biomedical subjects

S Möller

Publications and source records attributed to S Möller.

At least 37 records · Page 2Linked to original sources
PubMed1999

Congestive heart failure induces downregulation of P2X1-receptors in resistance arteries.

OBJECTIVE: Congestive heart failure (CHF) is accompanied by enhanced peripheral sympathetic nerve activity, increased vascular resistance and impaired peripheral blood flow. Besides noradrenaline and neuropeptide Y, the sympathetic nervous system also releases ATP, which has contractile effects mediated by different subtypes of P2-receptors on the vascular smooth muscle cells. The present study was designed to examine postsynaptic changes of the contractile responses to ATP and other extracellular nucleotides in CHF. METHODS: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague-Dawley rats. Contractile responses were examined in cylindrical segments of aorta and the mesenteric artery after endothelium removal. To determine if an altered response was regulated on the transcriptional level, competitive reverse transcription polymerase chain reaction (RT-PCR) was used to estimate the amount of P2X1-receptor mRNA. RESULTS: ATP, which is both a P2X1- and a P2Y-receptor agonist, induced a weaker contraction in the mesenteric artery from CHF as compared to sham operated rats. A decrease in both potency and maximum contraction was shown for the selective P2X1-receptor agonist, alpha beta-MeATP, in the mesenteric artery (pEC50 = 6.04 vs. 5.76, Cmax = 57% vs. 33%, sham vs. CHF operated rats), but not in the aorta. Competitive RT-PCR also revealed decreased P2X1-receptor mRNA levels in CHF operated rats in the mesenteric artery (9106 x 10(3) vs. 714 x 10(3) molecules/microgram, sham vs. CHF operated rats), while it remained unaltered in the aorta. To study the P2Y-receptor induced contractile effects, the P2X1-receptors were first desensitised with alpha beta-MeATP (10(-5) M for 8 min). After P2X1-receptors desensitisation, UTP and UDP induced strong contractions in both the mesenteric artery and in the aorta, while ATP and ADP were much less effective. These contractions were not altered by CHF, indicating that vascular contraction mediated by P2Y-receptors are unaffected by CHF. CONCLUSION: CHF induces downregulation of P2X1-receptor stimulated contraction in the mesenteric artery depending on decreased mRNA synthesis for the receptor, while the P2Y-receptor activity remains unchanged. Downregulation of P2X1-receptors appears to be specific for peripheral resistance arteries. This may represent a compensatory response to enhanced peripheral sympathetic nerve activity and increased vascular resistance in CHF.

Adenosine Diphosphate↗
PubMed1999

Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure.

We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.

Adolescent↗
PubMed1999

Expression of endothelin A- and B-receptors in human nasal mucosa.

Several studies have suggested an important role for the endothelin (ET) family of peptides in the vascular regulation of the nose. In addition, there is increasing evidence that ETs play a role in allergic airway inflammation. Endothelin is produced locally in the nose and mediates its effects via two distinct receptor subtypes, termed ET(A) and ET(B). Using reverse transcriptase-polymerase chain reaction, mRNAs encoding ET(A)- and ET(B)-receptors were detected in the human lower turbinate and sinus mucosa. The possibility of local release of ETs in connection with specific target receptors suggests a role for endothelin in the regulation of vascular tone, glandular secretion and epithelial functions.

Adult↗
PubMed1999

Expression of histamine H1 and H2 receptors in human nasal mucosa.

mRNA encoding histamine H1 and H2 receptors were detected in the human nasal mucosa using reverse transcriptase-polymerase chain reaction. The possibility of local release in connection with specific target receptors suggests a role for histamine in the regulation of vascular tone, glandular secretion and epithelial functions.

Adult↗
PubMed1999

EDITtoTrEMBL: a distributed approach to high-quality automated protein sequence annotation.

SUMMARY: Many databases in molecular biology face the problem that the ever increasing rate of data production can no longer be handled by traditional methods, especially human curation. Therefore, a number of projects are currently investigating methods for automated sequence annotation. This paper describes the EBI's approach to this problem for protein sequences by integration of arbitrary analysis programs into a distributed and highly flexible environment. Our software framework allows an individual treatment of sequences depending on their particular properties, which is achieved through a high-level description of the preconditions and capabilities of analysing modules. This not only improves the overall performance of the annotation process, as unnecessary steps are avoided, but also enhances its quality since dependencies between different modules are taken into account. We have implemented a prototype and use it in the production of TrEMBL releases. AVAILABILITY: Upon request.

Algorithms↗
PubMed1999

A novel method for automatic functional annotation of proteins.

MOTIVATION: To cope with the increasing amount of sequence data, reliable automatic annotation tools are required. The TrEMBL database contains together with SWISS-PROT nearly all publicly available protein sequences, but in contrast to SWISS-PROT only limited functional annotation. To improve this situation, we had to develop a method of automatic annotation that produces highly reliable functional prediction using the language and the syntax of SWISS-PROT. RESULTS: An algorithm was developed and successfully used for the automatic annotation of a testset of unknown proteins. The predicted information included description, function, catalytic activity, cofactors, pathway, subcellular location, quaternary structure, similarity to other protein, active sites, and keywords. The algorithm showed a low coverage (10%), but a high specificity and reliability. AVAILABILITY: The results can be obtained by anonymous ftp from ftp.ebi.ac.uk/pub/databases/sp_tr_nrdb. The source code is available on request from the authors.

Algorithms↗
PubMed1998

Phenotype changes of the vascular smooth muscle cell regulate P2 receptor expression as measured by quantitative RT-PCR.

Studies using selective agonists have suggested that the contractile effect of extracellular nucleotides, such as ATP and UTP, in blood vessels is mediated mainly by P2X1 receptors with a smaller contribution of P2Y receptors while the mitogenic effect is mediated by P2Y (P2Y1, P2Y2, P2Y4, and P2Y6) receptors with no effect of P2X1 receptors. This indicates a difference in P2 receptor expression between the contractile and the synthetic phenotype of the SMC. To measure the expression of mRNA for these receptors a competitive RT-PCR assay was developed that utilised synthetic RNA-competitors allowing determination of the number of mRNA copies for each receptor in the samples. In the synthetic phenotype the mitogenic P2Y1 and P2Y2 receptor transcripts were upregulated by 342- and 8-fold, respectively, while the contractile P2X1 receptor is totally downregulated and the P2Y4 and P2Y6 receptors were unchanged. This plasticity of the receptor expression may be important in the transition from the contractile to the synthetic SMC phenotype.

Adenosine Triphosphate↗
PubMed1998

Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice.

Apoptosis appears to play an important role in the development of diabetes in the non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the manifestation of insulin dependent diabetes mellitus (IDDM) can also affect the sympathochromaffin system, we analyzed the role of apoptosis and infiltration of the adrenal medulla as features of this autoimmune process in parallel with the development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks were studied and compared with control mice. Apoptosis was assessed by in situ end-labeling method and ultrastructural analysis. Adrenals were screened for lymphocytic infiltration by conventional hematoxylin-eosin staining. Chromaffin cells were characterized by immunohistochemical staining against synaptophysin and tyrosine hydroxylase. Apoptotic nuclei were detected in all mice studied at a very low level, mainly occuring within the connective tissue between medulla and cortex. The maximum score was achieved at 3 weeks (1.91+/-0.48 apoptotic cells/1000 counted cells; n = 4). There was no significant difference between NOD mice and control mice. No correlation could be found between blood glucose levels and apoptosis. On the ultrastructural level, apoptotic cells presented typical features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice nor in controls lymphocytic infiltration or fibrosis of the adrenal was detected. Even NOD mice with overt diabetes did not exhibit morphological signs of medullitis. In summary, no signs of immune destruction of the adrenal medulla in NOD mice aged 3 to 30 weeks could be detected.

Adrenal Cortex↗
PubMed1998

Increased levels of endothelin ETB receptor mRNA in human omental arteries after organ culture: quantification by competitive reverse transcription-polymerase chain reaction.

1. Using competitive reverse transcription-polymerase chain reaction (RT-PCR) and in vitro pharmacology, smooth muscle endothelin ETB receptor expression was studied in segments of human omental artery, fresh and after organ culture for 1 and 5 days. 2. The competitive RT-PCR assay used in the present study uses an internal RNA standard bearing a 69 b.p. deletion in order to control all steps of the reaction, including the RT step. Control experiments showed linearity over five subsequent 1:10 dilutions and a wide range of cycle numbers. The assay was able to quantify subattomolar concentrations in samples under 1 microgram total RNA, making it possible to measure mRNA expression even in small tissue biopsies. 3. In fresh arteries, ETB mRNA levels were 0.19 +/- 0.05 amol/microgram total RNA (range 0.03-0.42 amol/microgram; n = 8). After organ culture, an increase in ETB mRNA levels by 317 +/- 28 and 288 +/- 12% was found at days 1 and 5, compared with fresh arteries, respectively. 4. In vitro pharmacology showed that endothelin (ET)-1 induced a strong and potent contraction in fresh arteries, whereas the selective ETB receptor agonist IRL 1620 failed to induce a significant contraction. The ET-1-induced contraction was not altered in potency or Emax after organ culture for 1 and 5 days. In contrast, IRL 1620 induced a clear contraction after 1 day, which increased further in both Emax and potency after 5 days organ culture. 5. Our results indicate that a massive new transcription of ETB receptor mRNA is induced by organ culture, resulting in functional contractile ETB receptors on the smooth muscle layer.

Arteries↗
PubMed1998

Serotoninergic involvement in gonadotropin and TSH secretion in normal cycling and postmenopausal women.

We investigated the influence of a specific serotonin receptor blockade on pituitary hormone secretion in normal cycling women and postmenopausal women not receiving hormone replacement therapy. Serotonin receptor blockade was performed by using the HT-3 receptor subtype antagonist ondansetron as an i.v. bolus injection of 8 mg. Blood samples were taken before as well as 20, 30 and 40 min after ondansetron administration for the estimation of LH, FSH, and TSH. We could not find any hormonal changes in the normal cycling women. The postmenopausal women showed a significant decline in LH secretion, whereas FSH and TSH levels remained unchanged. Our results suggest serotoninergic involvement in LH secretion in postmenopausal hypoestrogenic hypergonadism.

Adult↗
PubMed1998

[Echinococcosis--case report and review of the literature].

Echinococcosis is a rare disease in central Europe. But with the increasing numbers of foreign citizens, this disease becomes more important in cases of cystic processes of unknown origin. It is still very difficult to achieve a diagnosis and a subsequent therapy, particularly in cases of multiple cysts, means a long lasting process containing certain risks. We report on a 20 years old female patient, suspected to have a severe inflammatory pelvic disease. We found multiple abdominal cysts, not originating from or involving ovaries, tubes, bowel, liver or kidneys. The serologic investigations proved our clinical suspicion on an echinococcosis. But neither serology nor clinical investigations could provide any indication on which kind of echinococcosis we found. We started a therapy with high doses of mebendazole to achieve a shrinkage of the multiple cysts to enable a surgery.

Adult↗
PubMed1997

Transcriptional regulated plasticity of vascular contractile endothelin ET(B) receptors after organ culture.

The aim of the present study was to investigate the level of regulation of the contractile endothelin ET(B) receptor which appears spontaneously after organ culture of vascular segments. Endothelin-1 elicited a strong contraction while the selective endothelin ET(B) receptor agonist, sarafotoxin 6c, had a negligible effect on fresh ring segments of rat mesenteric artery. After organ culture in serum-free Dulbecco's modified Eagle's medium at 37 degrees C (for 1 or 2 days) the endothelin-1-induced contraction was unchanged, whereas sarafotoxin 6c induced, after 1 day, a marked contraction which was further increased at day 2. The contraction induced by sarafotoxin 6c was significantly attenuated by the transcriptional inhibitor, actinomycin D, or the translational inhibitor, cyclohexamide, while the endothelin-1-induced contraction was much less affected. mRNA for endothelin ET(A) and endothelin ET(B) receptors was present in fresh human omental arteries denuded of endothelium. However, after organ culture, endothelin ET(B) mRNA was more prominent than endothelin ET(A) mRNA. Furthermore, the mRNA for both receptors was decreased after treatment with actinomycin D but not with cyclohexamide. This suggests that the endothelin ET(A) receptor is the dominating contractile receptor in fresh arteries while organ culture induces transcription and subsequent translation of contractile endothelin ET(B) receptors.

Animals↗
PubMed1996

Neuronal networks and self-organizing maps: new computer techniques in the acoustic evaluation of the infant cry.

Neuronal networks are computer-based techniques for the evaluation and control of complex information systems and processes. So far, they have been used in engineering, telecommunications, artificial speech and speech recognition. A new approach in neuronal network is the self-organizing map (Kohonen map). In the phase of 'learning', the map adapts to the patterns of the primary signals. If, the phase of 'using the map', the input signal hits the field of the primary signals, it resembles them and is called a 'winner'. In our study, we recorded the cries of newborns and young infants using digital audio tape (DAT) and a high quality microphone. The cries were elicited by tactile stimuli wearing headphones. In 27 cases, delayed auditory feedback was presented to the children using a headphone and an additional three-head tape-recorder. Spectrographic characteristics of the cries were classified by 20-step bark spectra and then applied to the neuronal networks. It was possible to recognize similarities of different cries of the same children as well as interindividual differences, which are also audible to experienced listeners. Differences were obvious in profound hearing loss. We know much about the cries of both healthy and sick infants, but a reliable investigation regimen, which can be used for clinical routine purposes, has yet not been developed. If, in the future, it becomes possible to classify spectrographic characteristics automatically, even if they are not audible, neuronal networks may be helpful in the early diagnosis of infant diseases.

Acoustics↗
PubMed1996

Matrix-isolation Raman spectroscopy and photochemistry of carbonyl-metal-silyl complexes.

To study the photochemistry of metal-silyl complexes the compounds Cp(CO)(2)Fe-SiH(2)(CH(3)) (Cp = eta(5)-C(5)H(5)) and Cp*(CO)(2)((CH(3))(3)P)Mo-SiH(3) (Cp* = eta(5)-C(5)(CH(3))(5)) have been isolated in krypton or nitrogen matrices and subsequently detected by Raman spectroscopy. Vibrational assignments for the two compounds are given. Furthermore, differences in the Raman spectra induced by UV irradiation are discussed.

Journal Article↗
PubMed1996

[Use of self-organizing neural networks (Kohonen maps) for classification of voice acoustic signals exemplified by the infant voice with and without time-delayed auditory feedback].

Subjective and auditory assessment of the voice is now more commonly being replaced by objective voice analysis. Because of the amount of data available from computer-aided voice analysis, subjective selection and interpretation of single data sets remain a matter of experience of the individual investigator. Since neuronal networks are widely used in telecommunication and speech recognition, we applied self-organizing Kohonen networks to classify voice patterns. In the phase of "learning," the Kohonen map is adapted to patterns of the primary signals obtained. If, in the phase of using the map, the input signal hits the field of the primary signals, it will resemble them closely. In this study, we recorded newborn and young infant cries using a DAT recorder and a high-quality microphone. The cries were elicited by wearing uncomfortable headphones ("cries of discomfort"). Spectrographic characteristics of the cries were classified by 20-step bark spectra and then applied to the neuronal networks. It was possible to recognize similarities of different cries of the same children and interindividual differences, as well as cries of children with profound hearing loss. In addition, delayed auditory feedback at 80 dB SL was presented to 27 children via headphone using a three-headed tape-recorder as a model for induced individual cry changes. However, it was not possible to classify short-term changes as in a delayed feedback procedure. Nevertheless, neuronal networks may be helpful as an additional tool in spectrographic voice analysis.

Acoustic Stimulation↗
PubMed1995

-Effect of endogenous opioids on adrenal cortex activity in women with hypothalamic amenorrhea-.

OBJECTIVE: Within an ovulation induction study, we investigated the activity and reactivity of the hypothalamic-pituitary-adrenal axis in women suffering from hypothalamic amenorrhea by using naloxone. METHODS: The central opioid receptors were blocked by means of a naloxone bolus injection of 4 mg i.v. daily. RESULTS: Before and after receptor blockade, the cortisol secretion showed diverse results independently from the hypothalamic opioid tone. The cortisol levels were not elevated. Also, the basal secretion of cortisol and DHEAS was nonspecific among the various responder groups. CONCLUSION: It seems that there is no close relationship between central opioid tone and adrenal function in hypothalamic amenorrhea.

Adult↗
PubMed1991

[Possibility of ovulation induction using naloxone in women with hypothalamic amenorrhea].

Within the study we treated 6 women suffering from hypothalamic amenorrhea with 4 mg naloxone intravenous daily. The duration of the study was at most 30 days. The estimation of hormonal baseline and changes occurs daily, furthermore everyday sonographic folliculometry. In 2 patients the chronic opiate receptor blockade leads to a drastic stimulation of gonadotropin secretion. One of these women (responder in Naloxone-Test) has a long standing elevation of LH and FSH resulting in an ovulation 2 days past end of the therapy. The other women (non-responder in Naloxone-Test) reaches a follicular growth till 17 mm follicle diameter following in preterm atresia during therapy. In another woman (minimal-responder in Naloxone-Test) occurs a short and weak elevation of gonadotropins without any basic stimulation of the hypothalamic-pituitary-ovary axis. The results of this study show that: 1. it's possible to discern an opioid mediated hypothalamic amenorrhea and 2. a Naloxone-Test or Naloxone-Stimulation-Test should be put before starting a therapy with opiate antagonists in hypothalamic amenorrhea.

Adult↗