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D Richter

Publications and source records attributed to D Richter.

At least 91 records · Page 5Linked to original sources
PubMed1999

Somatostatin receptor subtype 1 modulates basal inhibition of growth hormone release in somatotrophs.

Somatostatin (SST) inhibits the secretion of many peptide hormones including growth hormone (GH). The various functions of SST are mediated through at least five different receptor subtypes (SSTR1-5), their precise physiological roles have not been solved yet. Here we report on studies concerning the functional role of SSTR1 in the modulation of GH release from somatotrophs. Primary cell cultures from pituitaries of wild-type SSTR1 mice exposed to the SSTR1 selective somatostatin analog CH-275 show reduction of basal levels of GH secretion whereas somatotrophs isolated from SSTR1 null mutant mice did not respond to the agonist-mediated effect. This suggests that SSTR1 is involved in modulating basal GH levels in primary pituitary cell cultures and, together with SSTR2, may control the secretion of GH in the body.

Animals↗
PubMed1999

High-power continuous-wave mid-infrared radiation generated by difference frequency mixing of diode-laser-seeded fiber amplifiers and its application to dual-beam spectroscopy.

We report the generation of up to 0.7 mW of narrow-linewidth (<60-MHz) radiation at 3.3 micrometers by difference frequency mixing of a Nd:YAG-seeded 1.6-W Yb fiber amplifier and a 1.5-micrometers diode-laser-seeded 0.6-W Er/Yb fiber amplifier in periodically poled LiNbO3. A conversion efficiency of 0.09%/W (0.47 mWW-2 cm-1) was achieved. A room-air CH4 spectrum acquired with a compact 80-m multipass cell and a dual-beam spectroscopic configuration indicates an absorption sensitivity of +/-2.8 x 10(-5) (+/-1 sigma), corresponding to a sub-parts-in-10(9) (ppb) CH4 sensitivity (0.8 ppb).

Air Pollution, Indoor↗
PubMed1999

Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain.

By using the yeast two-hybrid system we identified a novel protein from the human brain interacting with the C terminus of somatostatin receptor subtype 2. This protein termed somatostatin receptor interacting protein is characterized by a novel domain structure, consisting of six N-terminal ankyrin repeats followed by SH3 and PDZ domains, several proline-rich regions, and a C-terminal sterile alpha motif. It consists of 2185 amino acid residues encoded by a 9-kilobase pair mRNA; several splice variants have been detected in human and rat cDNA libraries. Sequence comparison suggests that the novel multidomain protein, together with cortactin-binding protein, forms a family of cytoskeletal anchoring proteins. Fractionation of rat brain membranes indicated that somatostatin receptor interacting protein is enriched in the postsynaptic density fraction. The interaction of somatostatin receptor subtype 2 with its interacting protein was verified by overlay assays and coimmunoprecipitation experiments from transfected human embryonic kidney cells. Somatostatin receptor subtype 2 and the interacting protein display a striking overlap of their expression patterns in the rat brain. Interestingly, in the hippocampus the mRNA for somatostatin receptor interacting protein was not confined to the cell bodies but was also observed in the molecular layer, suggesting a dendritic localization of this mRNA.

Alternative Splicing↗
PubMed1999

Reverse physiology in drosophila: identification of a novel allatostatin-like neuropeptide and its cognate receptor structurally related to the mammalian somatostatin/galanin/opioid receptor family.

By using degenerate oligonucleotide primers deduced from the conserved regions of the mammalian somatostatin receptors, a novel G-protein-coupled receptor from Drosophila melanogaster has been isolated exhibiting structural similarities to mammalian somatostatin/galanin/opioid receptors. To identify the bioactive ligand, a 'reverse physiology' strategy was used whereby orphan Drosophila receptor-expressing frog oocytes were screened against potential ligands. Agonistic activity was electrophysiologically recorded as inward potassium currents mediated through co-expressed G-protein-gated inwardly rectifying potassium channels (GIRK). Using this approach a novel peptide was purified from Drosophila head extracts. Mass spectrometry revealed an octapeptide of 925 Da with a sequence Ser-Arg-Pro-Tyr-Ser-Phe-Gly-Leu-NH(2) reminiscent of insect allatostatin peptides known to control diverse functions such as juvenile hormone synthesis during metamorphosis or visceral muscle contractions. Picomolar concentrations of the synthesized octapeptide activated the cognate receptor response mediated through GIRK1, indicating that we have isolated the 394-amino-acid Drosophila allatostatin receptor which is coupled to the Gi/Go class of G proteins.

Amino Acid Sequence↗
PubMed1999

Identification of a cis-acting dendritic targeting element in MAP2 mRNAs.

In neurons, a limited number of mRNAs have been identified in dendritic processes, whereas other transcripts are restricted to the cell soma. Here we have investigated the molecular mechanisms underlying extrasomatic localization of mRNAs encoding microtubule-associated protein 2 (MAP2) in primary neuronal cultures. Vectors expressing recombinant mRNAs were introduced into hippocampal and sympathetic neurons using DNA transfection and microinjection protocols, respectively. Chimeric mRNAs containing the entire 3' untranslated region of MAP2 transcripts fused to a nondendritic reporter mRNA are detected in dendrites. In contrast, RNAs containing MAP2 coding and 5' untranslated regions or tubulin sequences are restricted to the cell soma. Moreover, 640 nucleotides from the MAP2 3' untranslated region (UTR) are both sufficient and essential for extrasomatic localization of chimeric mRNAs in hippocampal and sympathetic neurons. Thus, a cis-acting dendritic targeting element that is effective in two distinct neuronal cell types is contained in the 3' UTR of MAP2 transcripts. The observation of RNA granules in dendrites implies that extrasomatic transcripts seem to assemble into multimolecular complexes that may function as transport units.

3' Untranslated Regions↗
PubMed1999

Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1).

To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts were analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK). A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical with the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three N-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca(2+) dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G(i)- or G(q)-mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior.

Amino Acid Sequence↗
PubMed1999

Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1.

We report here an interaction between the C terminus of the rat somatostatin receptor subtype 2 (SSTR2) and a protein that has recently been identified as cortactin-binding protein 1 (CortBP1). Interaction is mediated by the PDZ (PSD-95/discs large/ZO-1) domain of CortBP1. As shown by in situ hybridization, SSTR2 and cortactin-binding protein are coexpressed in the rat brain. The association between SSTR2 and the PDZ-domain of CortBP1 was verified by overlay assays and by coprecipitation after transfection in human embryonic kidney (HEK) cells. Analysis by confocal microscopy indicates that CortBP1 is distributed diffusely throughout the cytosol in transfected cells and that it becomes concentrated at the plasma membrane when SSTR2 is present. This process is largely increased when the receptor is stimulated by somatostatin; as CortBP1 interacts with the C terminus of SSTR2, our data suggest that the binding of agonist to the receptor increase the accessibility of the receptor C terminus to the PDZ domain of CortBP1. Our data for the first time establish a link between a G-protein coupled receptor and constituents of the cytoskeleton.

Amino Acid Sequence↗
PubMed1999

Unusual mutations in Btk: an insertion, a duplication, an inversion, and four large deletions.

Mutations in Bruton's tyrosine kinase (Btk) result in the immunodeficiency X-linked agammaglobulinemia (XLA). In a previous study of 101 patients with presumed XLA, we identified seven patients with large genomic alterations in Btk. The recent completion of 100 kb of contiguous DNA sequence at the Btk locus has allowed us to characterize these mutations in detail and to identify four different types of alterations. These alterations included a 253-bp retroposon insertion at position +5 within intron 9, an inversion of greater than 48 kb that disrupted Btk between exons 4 and 5, a 12.9-kb duplication including Btk exons 2 to 5, and four deletions ranging from 2.8 to 38 kb in size. The duplication and three of the deletions resulted from unequal crossovers of Alu repeats. Further, three of the deletions terminated within a repeat-rich cluster spanning 30 kb of sequence 3' of Btk exon 19, suggesting that this region was more susceptible to unequal crossovers than the rest of the Btk gene. These studies describe the first reports of an insertion, an inversion, and a duplication in Btk and demonstrate the utility of large-scale sequencing in the elucidation of disease-causing mutations.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1999

[Pediatric forearm fractures: indications, technique, and limits of conservative management].

Although several "minimal invasive" techniques for the operative management of pediatric forearm fractures have been developed recently, conservative treatment still remains the option with the lowest risk for small patients. We present the results of our clinical and radiological follow-up after an average of 52.4 months (4-112) in 102 pediatric patients. All fractures were treated conservatively. There were 68 fractures (66.7 %) of the distal third of the forearm, 30 fractures (29.4 %) of the midshaft area, and four fractures (3.9 %) in the proximal third of the shaft. Greenstick fractures were seen in 58 cases (56.8 %), complete fractures with displacement of both corticalices in 26 patients (25.5 %), and folding fractures in 18 cases (17.7 %). With the exception of one fracture with the necessity of remanipulation after redisplacement in the cast, all fractures healed uneventfully without any further intervention. Functional results were excellent with a free range of motion of the wrist and elbow and without any signs of muscular atrophy in 96 children (94.1 %) at the time of follow-up. Six patients, however, showed a significant loss of forearm rotation of an average of 25 degrees (15 degrees -50 degrees ). In four of these six patients, the fracture had been situated in the proximal and midshaft area. Thus, two out of four fractures of the proximal forearm (50.0 %) showed a poor functional outcome. On the basis of our data we recommend conservative management for (closed) pediatric fractures of the distal and midshaft area. Operative treatment is indicated in forearm fractures close to the elbow.

Adolescent↗
PubMed1999

Multiple genes for neuropeptides and their receptors: co-evolution and physiology.

It is now well established that neuropeptide receptors, which are present throughout the CNS and in peripheral tissues, frequently exist in a variety of different forms (called subtypes), each of which is encoded by a distinct gene. With the recent identification of new neuropeptide genes, it has become clear that families of neuropeptides also occur, which raises the possibility that specific peptide ligands activate particular receptor subtypes preferentially. This article reviews some of the recent advances in the neuropeptide field and provides evidence in support of three ideas: (1) that different receptor subtypes for a given ligand can be distinguished physiologically; (2) that neuropeptide genes probably arose before the corresponding receptor genes; and (3) that, despite the current wealth of information on neuropeptides and neuropeptide receptors, several new members are likely to be discovered before the beginning of the next millennium.

Animals↗
PubMed1999

Chronic mental illness and the limits of the biopsychosocial model.

Twenty years ago, the biopsychosocial model was proposed by George Engel to be the new paradigm for medicine and psychiatry. The model assumed a hierarchical structure of the biological, psychological and social system and simple interactions between the participating systems. This article holds the thesis that the original biopsychosocial model cannot depict psychiatry's reality and problems. The clinical validity of the biopsychosocial model has to be questioned. It is argued that psychiatric interventions can only stimulate but not determine their target systems, because intervention and outcome are only loosely coupled. Thus, psychiatric interventions have in principle limited ranges which differ according to the type of intervention and according to the system to be stimulated. Psychosocial interventions face far more obstacles to be overcome than psychopharmacological therapy.

Chronic Disease↗
PubMed1999

Prolonged adjustment difficulties among those with acute posttrauma distress following burn injury.

This study examined the impact of mild to moderate symptoms of in-hospital posttrauma distress (PTD) following severe burn injury on quality of life (QOL) at 2-month follow-up after controlling for preburn QOL, injury severity, and state Negative Affectivity (depression, body image dissatisfaction) and dispositional optimism-pessimism. Participants' (n = 86) self-report established PTD and non-PTD groups (median split on Davidson Trauma Scale). After covarying preburn level of psychosocial QOL, PTD groups differed on psychosocial functioning at follow-up. This effect remained after covarying injury severity, state NA, dispositional optimism-pessimism, and preburn Mental domain QOL. PTD groups also differed significantly on physical functioning at follow-up after covarying preburn physical functional status. This effect was removed by controlling preburn Physical domain QOL and either injury severity or state NA and dispositional optimism-pessimism. Therefore, PTD is related to significant impairments in the physical and psychosocial adjustment of survivors of severe burns regardless of pretrauma level of adjustment. Injury severity and state NA and dispositional optimism-pessimism moderate the impact of PTD on physical but not psychosocial adjustment.

Activities of Daily Living↗
PubMed1999

Agonist-independent internalization and activity of a C-terminally truncated somatostatin receptor subtype 2 (delta349).

The rat somatostatin receptor subtype 2 (SSTR2) is rapidly internalized and phosphorylated in the presence of somatostatin 14 (SST14). Several C-terminal deletion constructs of SSTR2 have been investigated for their ability to undergo agonist-dependent internalization by using biochemical ligand binding assays and confocal microscopic analysis. Whereas mutant receptors lacking either 10 (delta359), 30 (delta339), or 44 (delta325) amino acid residues at the C terminus required SST14 for internalization, a construct lacking the last 20 amino acids (delta349) was detected mostly intracellularly and independently of the presence of the agonist. When internalization was blocked by sucrose, the delta349 receptor remained at the cell surface, strongly indicating that this mutant is internalized in an agonist-independent fashion. An increased affinity for agonists as measured in membrane binding assays and a reduced level of forskolin-stimulated cyclic AMP accumulation in human embryonic kidney cells expressing delta349 are properties that are characteristic of agonist-independent receptor activity. Delta349 is not phosphorylated detectably in the absence of agonist, demonstrating that phosphorylation per se is not a prerequisite for internalization of SSTR2. This observation is in line with data obtained for the delta325 mutant, which was internalized in an agonist-dependent manner, but not phosphorylated in either the presence or absence of SST14. We conclude that truncation of the SSTR2 C terminus at position 349 leads to agonist-independent, constitutive activity and internalization.

Amino Acid Sequence↗
PubMed1999

[What characterizes the problem psychiatric patient? Results of a study of patient descriptions using the Psychiatric Personnel Order].

In recent years, economic pressure on extended and repeated psychiatric hospitalisation have increased dramatically. At the same time, diagnostic approaches, e.g., the new concept of the "young adult chronic patient" have improved. The first part of this article summarises reports and experiences on the chronic mentally ill and the so-called "heavy users" of psychiatric hospitalisation. Although the number of studies evaluating this group is small, several characteristics can be identified. Subsequently, a study is presented that deals with psychiatric problem patients in a special way, namely the A2-categorisation according to the German Psychiatric Personnel Regulation (Psychiatrie-Personalverordnung [Psych-PV]). The study is based on 170 consecutive admissions to the Department of General Psychiatry of a large German state hospital, who are characterised as normal (A1) and intensive patients (A2), respectively. The study aimed at describing difficult-to-treat patients or those whose treatment demands large human resources. Medical histories, sociodemographic and psychopathological data as well as subjective health status data of these patients were analysed by standardised and validated instruments (e.g., BPRS, CGI, SF-36, GAF). Results show that the patients under study suffered mainly from schizophrenic psychosis according to ICD-9. Patients categorised into A2 showed a high degree of psychopathology and little insight into their disease. Further it can be demonstrated that they used more therapeutic help from general practitioners rather than from specialists in psychiatry prior to admission. In conclusion, it is suggested to evaluate concepts, e.g., new treatment methods in respect of motivating schizophrenic patients, new typological methods to better diagnosis and to treat psychiatric problem patients via new treatment modalities such as Case Management or inpatient settings for double diagnoses.

Adult↗
PubMed1999

Postprandial lipid, glucose, insulin, and cholecystokinin responses in men fed barley pasta enriched with beta-glucan.

BACKGROUND: Fiber regulates the rate and site of lipid and carbohydrate digestion and absorption and thus can modify the alimentary responses to a meal. When fiber sources containing viscous polysaccharides are included in a meal, a slower rate of carbohydrate and lipid absorption will modify the alimentary hormone and lipid responses. OBJECTIVE: We investigated in 11 healthy men the response of insulin, glucose, cholecystokinin, and lipid to 2 test meals containing beta-glucan. DESIGN: One of the meals was high in fiber (15.7 g) and the other meal was low in fiber (5.0 g). The low-fiber meal contained pasta made with wheat flour. The high-fiber meals contained pasta prepared by replacing 40% of the wheat with 2 types of barley flour: barley naturally high in beta-glucan and the other a flour enriched in beta-glucan during processing. RESULTS: Plasma glucose and insulin concentrations increased significantly after all meals but the insulin response was more blunted after the barley-containing meals. The test meals were low in fat (25% of energy) but elicited an increase in plasma triacylglycerol and cholecystokinin. Cholecystokinin remained elevated for a longer time after the barley-containing meals. After the low-fiber meal, plasma cholesterol concentrations did not change significantly; however, 4 h after the barley-containing meals, the cholesterol concentration dropped below the fasting concentration and was significantly lower than that after the low-fiber meal. CONCLUSIONS: Carbohydrate was more slowly absorbed from the 2 high-fiber meals. Consumption of the barley-containing meals appeared to stimulate reverse cholesterol transport, which may contribute to the cholesterol-lowering ability of barley.

Adult↗
PubMed1999

Arthrodesis of the infected ankle and subtalar joint: technique, indications, and results of 45 consecutive cases.

OBJECTIVE: To analyze the results of 45 patients after ankle arthrodesis in the presence of joint infection. METHODS: Arthrodesis was performed with two compression screws and an anterior plate in 29 patients and with two compression screws only in 16 patients. In all patients, additional stabilization with external fixation was used. In 29 patients, isolated fusion of the ankle joint was performed; in 13 patients, the ankle and subtalar joints were fused, and in 3 patients, isolated arthrodesis of the subtalar joint was performed. RESULTS: In 39 of 45 patients (86.6%), solid fusion was obtained. Nonunions occurred in 6 patients (13.4%). A below-knee amputation was necessary for one patient. Full weight-bearing was achieved after 21.6 weeks on average. Thirty-two patients returned to work after 35.5 weeks on average. Five of the six patients with failed ankle fusion needed special shoes; in one patient, a below-knee amputation was performed. A total of 33.3% of failed ankle fusions were associated with systemic disorders such as diabetes mellitus, and other concomitant diseases compromising local arterial blood supply and proprioception. CONCLUSION: Our results prove that limb salvage is possible even in complex ankle and subtalar pathology by thorough fusion by using a number of different techniques.

Adult↗