Antiquity of the Lyme-disease spirochaete in Europe.
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Animals↗
Biomedical subjects
D Richter
Publications and source records attributed to D Richter.
Effect of hypoosmolality on the abundance, poly(A) tail length and axonal targeting of arginine vasopressin and oxytocin mRNAs in rat hypothalamic magnocellular neurons.
Arginine vasopressin (AVP) and oxytocin (OT) mRNAs are targeted to the axonal compartment of rat hypothalamic magnocellular neurons. Salt-loading results in a considerable rise in hypothalamic and axonal AVP mRNA but only a moderate increase for axonal OT mRNA. Here we report that hypoosmolality gives rise to a rapid decrease of axonal AVP encoding transcripts to undetectable levels after 2 weeks. The levels of OT mRNA in the axonal compartment did not change significantly. In the hypothalamus the mRNA for AVP also decreased. The size of the poly(A) tract of AVP encoding transcripts appeared to be strictly correlated with plasma osmolality. In contrast, the amount and size of OT encoding mRNAs were only moderately or not influenced by hypoosmolar stimuli.
Animals↗
Teleost isotocin receptor: structure, functional expression, mRNA distribution and phylogeny.
A cDNA encoding a receptor for the oxytocin-related peptide isotocin has been identified by screening a lambda gt11 library constructed from poly(A)+ RNA of the hypothalamic region of the teleost Catostomus commersoni. The probe used was obtained by PCR amplification of white sucker genomic DNA using degenerate primers based on conserved sequences in the mammalian receptor counterparts. The full-length cDNA specifies a polypeptide of 390 amino acid residues that displays the typical hydrophobicity profile of a seven transmembrane domain receptor and which exhibits greatest similarity to mammalian oxytocin receptors. Oocytes that express the cloned receptor respond to the application of isotocin by an induction of membrane chloride currents indicating that it is coupled to the inositol phosphate/calcium pathway. The isotocin receptor (ITR) can also be activated by vasotocin, mesotocin, oxytocin and Arg-vasopressin, although these have lower potencies than isotocin. ITR-encoding mRNA has been detected in brain, intestine, bladder, skeletal muscle, lateral line, gills and kidney indicating that this receptor may mediate a variety of physiological functions.
Amino Acid Sequence↗
Differential subcellular mRNA targeting: deletion of a single nucleotide prevents the transport to axons but not to dendrites of rat hypothalamic magnocellular neurons.
It has previously been shown that mRNA encoding the arginine vasopressin (AVP) precursor is targeted to axons of rat magnocellular neurons of the hypothalamo-neurohypophyseal tract. In the homozygous Brattle-boro rat, which has a G nucleotide deletion in the coding region of the AVP gene, no such targeting is observed although the gene is transcribed. RNase protection and heteroduplex analyses demonstrate that, in heterozygous animals, which express both alleles of the AVP gene, the wild-type but not the mutant transcript is subject to axonal compartmentation. In contrast, wild-type and mutant AVP mRNAs are present in dendrites. These data suggest the existence of different mechanisms for mRNA targeting to the two subcellular compartments. Axonal mRNA localization appears to take place after protein synthesis; the mutant transcript is not available for axonal targeting because it lacks a stop codon preventing its release from ribosomes. Dendritic compartmentation, on the other hand, is likely to precede translation and, thus, would be unable to discriminate between the two mRNAs.
Animals↗
A novel G protein-coupled receptor mediating both vasopressin- and oxytocin-like functions of Lys-conopressin in Lymnaea stagnalis.
We have cloned a receptor, named LSCPR, for vasopressin-related Lys-conopressin in Lymnaea stagnalis. Lys-conopressin evokes Ca(2+)-dependent Cl- currents in Xenopus oocytes injected with LSCPR cRNA. Expression of LSCPR mRNA was detected in central neurons and peripheral muscles associated with reproduction. Upon application of Lys-conopressin, both neurons and muscle cells depolarize owing to an enhancement of voltage-dependent Ca2+ currents and start firing action potentials. Some neurons coexpress LSCPR and Lys-conopressin, suggesting an autotransmitter-like function for this peptide. Lys-conopressin also induces a depolarizing response in LSCPR-expressing neuroendocrine cells that control carbohydrate metabolism. Thus, in addition to oxytocin-like reproductive functions, LSCPR mediates vasopressin-like metabolic functions of Lys-conopressin as well.
Amino Acid Sequence↗
Hydration dependence of chain dynamics and local diffusion in L-alpha-dipalmitoylphosphtidylcholine multilayers studied by incoherent quasi-elastic neutron scattering.
Incoherent quasi-elastic neutron scattering is applied to study the local diffusion and chain dynamics of L-alpha-diplamiotylphosphatidylcholine molecules in oriented model membranes. Different motions are distinguished by changing the hydration of the multilayers as well as by measuring below and above the gel-to-liquid crystalline phase transition. The time range of the utilized time-of-flight spectrometer permits to observe two types of motion to be observed more closely: chain defect motions and the local diffusion of the whole molecule in its solvation cage. Oriented lipid membranes are a useful system for the observation of chain defects, as they can be macroscopically oriented, in contrast to most polymers. As a representative model for a chain defect a kink is chosen and the corresponding scattering functions are derived. The kink motion can explain the entire dynamics seen in the gel phase, and the lifetime of such a defect was found to be 10-15 ps, in good agreement with theoretical predictions. On the other hand the dynamics in the liquid crystalline phase cannot be explained even by a superposition of several kinks and thus requires the consideration of an additional motion: the local diffusion of the molecule in its solvation cage. The size of the solvation cage is increasing with multilayer hydration and reduced temperature. Particularly interesting in view of recent discussions about the origin of the short-range repulsive forces between membranes is the experimental finding of an out-of-plane motion with an amplitude of 1-1.5 A, which cannot be explained by the undulation of the whole membrane.
1,2-Dipalmitoylphosphatidylcholine↗
Vasopressin and oxytocin: molecular biology and evolution of the peptide hormones and their receptors.
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Amino Acid Sequence↗
Aspartic acid residue 124 in the third transmembrane domain of the somatostatin receptor subtype 3 is essential for somatostatin-14 binding.
A highly conserved aspartic acid residue present in the third membrane-spanning region of adrenergic and muscarinic receptors is directly involved in ligand binding. The five cloned somatostatin receptor subtypes also contain this residue at the same relative position. To test whether Asp-124 of the rat somatostatin receptor subtype 3 (SSTR3) is responsible for the binding of somatostain-14 (SST-14), this amino acid residue was replaced by an asparagine or a glutamic acid by polymerase chain reaction (PCR)-mediated site-directed mutagenesis. Expression and binding activity of the wild-type and mutant receptor constructs were studied in COS and HEK cells by ligand binding, UV cross-linking, Western blot, and immunocytochemical analysis. The Asn or Glu mutations result in a significant loss of SST-14 binding, although the mutant receptors are correctly transferred to the cell surface, demonstrating that Asp-124 is directly involved in binding of SST-14.
Amino Acid Sequence↗
[Expectations from digital imaging and archiving procedures].
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Computer Security↗
[Extracorporeal shock wave therapy--an alternative concept for the treatment of epicondylitis of the humerus and radius?].
In a prospective study, 16 patients with chronic, painful epicondylitis humeri radialis were treated with extracorporal high-energy shock waves. A complaint-free period of 3 months was achieved in 13 patients. In 2 of them complete release from pain was achieved for more than 3 months. We conclude that release from the symptoms is achieved by local hyperemia in the area of tendinitis. In contrast to the encouraging observations of other authors, our results suggest that a critical view of extracorporal shock waves for the treatment of chronic epicondylitis radialis of the elbow is reasonable.
Adult↗
[Ventral hyperostosis of the cervical spine--a rare differential diagnosis of dysphagia].
A case of dysphagia and hoarseness due to external compression by anterior hyperostosis between the third and fourth cervical vertebra is reported. Immediate relief of the symptoms was accomplished by surgical excision of the hyperostosis through an antero-lateral approach. The pathogenesis of the symptoms with reference to literature is discussed.
Cervical Vertebrae↗
Structure, function, and phylogeny of [Arg8]vasotocin receptors from teleost fish and toad.
[Arg8]Vasotocin (AVT) is considered to be the most primitive known vertebrate neurohypophyseal peptide of the vasopressin/oxytocin hormone family and may thus be ancestral to all the other vertebrate peptide hormones. The molecular evolution of the corresponding receptor family has now been studied by cloning an AVT receptor, consisting of 435 amino acid residues, from the teleost fish, the white sucker Catostomus commersoni. Frog oocytes injected with the AVT receptor-encoding cRNA respond to the application of AVT, but not to its structural and functional counterpart isotocin, by an induction of membrane chloride currents indicating the coupling of the AVT receptor to the inositol phosphate/calcium pathway. The pharmacological properties of the expressed AVT receptor show that it represents, or is closely related to, an ancestral nonapeptide receptor: oxytocin, aspargtocin, mesotocin, and vasopressin activated the receptor, but other members of the vasopressin/oxytocin family tested showed little or no potency; antagonists of the mammalian vasopressin V1 and oxytocin receptors blocked the AVT response. Comparison of AVT receptor sequences spanning transmembrane domains two to five, deduced by cloning cDNAs from the Pacific salmon Oncorhynchus kisutch, the cave-dwelling fish Astyanax fasciatus, and the anuran Xenopus laevis, with those of their mammalian counterparts emphasizes amino acid residues that are involved in hormone binding. The presence of a 5.0-kb transcript in various teleost tissues (pituitary, liver, gills, swim bladder, and lateral line) points to a physiological role for the fish AVT receptor in metabolic, osmoregulatory, and sensory processes.
Amino Acid Sequence↗
Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.
BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.
Adolescent↗
Existentialism and postmodernism. Continuities, breaks, and some consequences for medical theory.
Since existentialism lost its influence in philosophy in the 1960s, postmodern theory has taken over criticizing basic concepts of western thought. From a postmodern point of view, the main shortcomings of existentialism is that it criticizes traditional unitarian concepts, while re-inventing new unitarian models. Against these unitarian approaches postmodernism holds that the world can only be described in terms of difference. In this article the postmodern program and its differences from existentialism are explained in reference to three concepts of western philosophy: subject, truth, and ethics. Applying these concepts, the relevance of postmodernism for medical theory is illustrated.
Ethics↗
Dendritic and axonal mRNA trafficking.
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Animals↗
Changes in plasma and hepatic lipids, small intestinal histology and pancreatic enzyme activity due to aging and dietary fiber in rats.
Rats were fed either a control diet or a control diet supplemented with wheat bran, psyllium husk or oat bran to increase intake of fiber. Groups of rats were killed after 3.5, 10, 15, or 18.5 mo of consuming the diets. Plasma cholesterol and triglyceride concentrations were significantly higher in 18.5-mo-old than younger animals. Fiber supplementation did not prevent the age-related increase in lipids. Cecal weight, including contents, was higher in the psyllium husk and oat bran groups than control, and smooth muscle thickness in the ileum of psyllium husk and oat bran animals was greater than control. The score for torn villi in the small intestine was lower than expected in the wheat bran group. Amylase activity in the pancreas declined significantly with age in all groups. In aging animals fiber supplementation may enhance ileal compensation for decreases in proximal intestinal function but does not prevent age-related changes in the gut or in lipid concentrations.
Aging↗
Mitochondrial cardiomyopathy and scapuloperoneal spinal muscular atrophy in a child.
A 14-year old boy was admitted for signs of heart failure and scapuloperoneal muscle weakness. He fulfilled the clinical, functional and diagnostic criteria for dilated cardiomyopathy. There was also a moderate increase in pulmonary vascular resistance. The immunohistochemical examination of the heart muscle revealed a slightly positive phytohemagglutinin reaction and minimal IgM deposits without complement. The electron microscopy examination disclosed increased numbers of abnormal mitochondria disrupting the usual cell structure; the mitochondria were of various sizes with irregular and abnormal structure of the cristae. The scapuloperoneal spinal muscular atrophy was mild and diagnosed according to clinical and electromyographic findings. Light microscope examination of the skeletal muscle revealed hypotrophic fibers. This patient is presumed to have postinflammatory mitochondriopathy and is currently being managed on low-dose digitalis, diuretics and captopril.
Adolescent↗
Rat insulin-degrading enzyme: cleavage pattern of the natriuretic peptide hormones ANP, BNP, and CNP revealed by HPLC and mass spectrometry.
The degradation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) by insulin-degrading enzyme (IDE) has been investigated. As revealed by high-performance liquid chromatography, all three peptides are sequentially cleaved at a limited number of sites, the latter of which were identified by mass spectrometric analyses. The studies revealed that ANP is preferred as substrate over BNP and CNP. ANP degradation is rapidly initiated by hydrolysis at the Ser25-Phe26 bond. Three additional cleavage sites were identified in ANP after prolonged incubation with IDE; in contrast, three and two bonds were hydrolyzed in BNP and CNP, respectively. Analysis of the nine cleavage sites shows a preference for basic or hydrophobic amino acid residues on the carboxyl side of a cleaved peptide bond. In contrast to most of the peptide fragments generated by IDE activity, the initial ANP cleavage product, F-R-Y, is rapidly degraded further by cleavage of the R-Y bond. Cross-linking studies with 125I-ANP in the presence of sulfhydryl-modifying agent indicate that IDE activity is inhibited at the level of initial substrate binding whereas metal-ion chelating agents only prevent hydrolysis. On the basis of its structural and enzymatic properties, IDE exhibits striking similarity to a number of recently-described endopeptidases.
Amino Acid Sequence↗