Sporadic Creutzfeldt-Jakob disease in a 16-year-old in the UK.
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Adolescent↗
Biomedical subjects
C Shaw
Publications and source records attributed to C Shaw.
Neisseria gonorrhoeae with decreased susceptibility to ciprofloxacin in British Columbia: an imported phenomenon.
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Anti-Infective Agents↗
The natriuretic peptide family.
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Amino Acid Sequence↗
The regional distribution of neuropeptides in human skin as assessed by radioimmunoassay and high-performance liquid chromatography.
In this study radioimmunoassay was used to determine neuropeptide levels in extracts from 17 differing anatomical regions of human skin. Marked regional variations of neuropeptide content for human skin were found and these variations are likely to reflect true physiological functions for the neuropeptides studied. In general the tachykinins, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were found in highest concentrations in regions of skin with the greatest tactile sensation. By contrast, highest concentrations of vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) were found in axillary skin, where they probably play a part in axillary eccrine sweat production. Neurotensin was not found in any of the skin areas sampled, suggesting that it is relatively unimportant in human physiological skin control. Reverse-phase high-performance liquid chromatography (rpHPLC) was used to verify the results of radioimmunoassay. Both SP and NKA occurred in several regions in both their reduced and oxidized forms, as well as displaying molecular heterogeneity. CGRP occurred as one molecular species, this being alpha-CGRP, suggesting that this is the predominant molecular form in human skin. Likewise, both VIP and PHM displayed molecular homogeneity in the regions investigated by rpHPLC.
Adult↗
Cytochemical observations on the nervous system of adult Corrigia vitta.
Adult Corrigia vitta (Trematoda: Dicrocoelidea) inhabit the pancreatic duct of the fieldmouse, Apodemus sylvaticus, where, in numbers, they may occlude the duct lumen and prevent the flow of pancreatic secretions. Enzyme histochemical and immunocytochemical techniques, in conjunction with confocal scanning laser microscopy, have been used to examine the localization and distribution of cholinergic, serotoninergic (5-HT, serotonin) and peptidergic components of the nervous system of the adult worm. All three classes of neuronal mediator showed a common pattern of staining, occurring throughout the central and peripheral nervous systems. Of the four peptide immunoreactivities (IR) demonstrated (pancreatic polypeptide (PP), peptide YY (PYY), substance P (SP), FMRFamide), PP-IR was the most predominant, occurring not only within the central ganglia and longitudinal nerve cords, but also in subtegumental plexuses and in fibres associated with the egg-forming apparatus. PYY and FMRFamide IRs were evident throughout the central and peripheral nervous systems; FMRFamide immunostaining, in particular, highlighted innervation of the ootype and immunoreactive cell bodies around the Mehlis' gland. Both SP- and 5-HT-IRs were restricted to the cerebral ganglia, ventral nerve cords and associated cell bodies. The distribution patterns of these peptides and 5-HT within the nervous system of C. vitta suggest they are likely to function as neuronal mediators. PP, PYY and FMRFamide may also serve in regulating egg production.
Animals↗
The primary structure of TE-6: a novel neuropeptide from the nematode Ascaris suum.
Extensive immunoreactivity (IR) towards a hexapeptide (sequence KGQELE), which flanks the C-terminus of the pancreastatin sequence in rat chromogranin A (CGA), is found throughout the nervous system of the nematode parasite Ascaris suum. The peptide IR was purified from the gonoduct of the parasite and found to have the sequence TKQELE. This peptide, designated TE-6, has some C-terminal homology with several regions of the CGA molecule. However, TE-6 was the only peptide isolated suggesting that either the nematode does not possess CGA, or that the -ELE regions of parasite CGA-like peptides which would be larger than TE-6 are not accessible to the antiserum in RIA, or are not being successfully extracted from the parasite. The N-terminus of TE-6 has little homology with any of the sequences preceding -ELE regions in CGA. This, and the fact that the tissue from which TE-6 was isolated does not contain IR towards another, highly conserved, region of the CGA molecule (WE-14) suggests that TE-6 may belong to a new class of regulatory peptide unrelated to CGA.
Amino Acid Sequence↗
The primary structure of neuropeptide F (NPF) from the garden snail, Helix aspersa.
Neuropeptide F (NPF), originally isolated from the sheep tapeworm, Moniezia expansa, consists of 39 amino acid residues terminating in a phenylalaninamide. An analogous neuropeptide has been isolated and sequenced from extracts of circumoesophageal ganglia of the garden snail, Helix aspersa. This neuropeptide exhibits partial primary structural similarity to members of the vertebrate neuropeptide Y (NPY)/pancreatic polypeptide (PP) superfamily. NPF is thus of widespread occurrence in the nervous systems of invertebrates from different phyla and may represent the phylogenetic precursor of the vertebrate NPY/PP superfamily.
Amino Acid Sequence↗
Cortical AMPA receptors: age-dependent regulation by cellular depolarization and agonist stimulation.
We have recently shown that a high-affinity AMPA receptor labelled with the antagonist [3H]CNQX can be regulated in a 'living' cortical slice preparation by agonist stimulation or changes in electrical activity (Lanius, R.A. and Shaw, C. (1992) Anat. Rec., in press). Based on a study of GABAA receptors (Shaw, C. and Scarth, B.A. (1992) Mol. Brain Res., in press), which showed age-dependent changes in regulation, we have now investigated the regulation of high-affinity AMPA receptors in neocortex at different stages in postnatal development. The results show that regulation by agonist stimulation and increases in bioelectric activity are age-dependent in amount and, in the latter case, in direction. Agonist stimulation using quisqualate resulted in a significant receptor down-regulation of approximately 7% at ages less than 20 days postnatal; in adult rats quisqualate led to a significant 23% decrease. Changes in bioelectric activity induced by a combination of veratridine and glutamate showed a significant increase in AMPA receptor number of 16% at ages less than 20 days, whereas such treatment resulted in a significant 18% decrease in adult rats. The present data reveal a near mirror-image to the effects of veratridine and glutamate and agonist on GABAA receptors in the same preparation, but with a temporal mismatch in the amount and direction of regulation. We speculate that the age-dependent differences in direction of regulation for the receptor populations which serve key excitatory and inhibitory functions in cortex may provide a molecular basis for the gradual decline of neuronal plasticity during the critical period.
Aging↗
Peptide tyrosine phenylalanine: a novel neuropeptide F-related nonapeptide from the brain of the squid, Loligo vulgaris.
A novel nonapeptide, sequence YAIVARPRFamide, was isolated from brain extracts of the squid, L. vulgaris. Designated peptide tyrosine phenylalanine (PYF), the peptide shows marked homology with the C-terminal nonapeptides of pancreatic polypeptide and neuropeptide F (NPF) from a number of sources. If PYF is the C-terminal nonapeptide of squid NPF, then it may be derived by a novel processing mechanism involving specific cleavage between two TYR residues. PYF may be a highly truncated, receptor-active variant of NPF.
Amino Acid Sequence↗
Different relative abundance of neurotensin and neuromedin N in bovine ocular tissues.
Neurotensin (NT) and neuromedin N (NN) are regulatory peptides encoded by the same gene and located in tandem within a common precursor. Using specific radioimmunoassays for both peptides, their relative abundance in extracts of bovine ocular tissues has been examined. Within the retina, the molar concentration of NN was significantly higher (P less than 0.001) than that of NT. In contrast, within both choroid/sclera and iris/ciliary bodies, the molar concentration of NT was significantly higher (P less than 0.001) than that of NN. These data demonstrate that the theoretical molar ratio of 1:1, which would result from complete processing of both peptides from the common precursor, does not occur in any of the ocular tissues examined. Reverse phase HPLC of extracts of each ocular tissue confirmed the differential abundance of NT and NN. These data would suggest that the common NT/NN precursor is differentially-processed within bovine ocular tissues, a finding which may be of physiological significance.
Animals↗
Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour.
The primary structure of a novel human chromogranin A-derived tetradecapeptide, WE-14, possessing N-terminal tryptophanyl (W) and C-terminal glutamyl (E) residues was isolated from a hepatic metastasis of an human ileal carcinoid tumour. Human and bovine WE-14 are structurally identical, while rat, mouse and porcine analogues exhibit 93% homology. WE-14 is flanked by paired basic residues (KR) in all known chromogranin A sequences.
Amino Acid Sequence↗
Isolation and primary structure of an amphibian neurotensin.
Using a radioimmunoassay system employing an antiserum which recognises the common C-terminal tripeptide (YIL) of neurotensin (NT) and neuromedin N (NN), immunoreactivity was identified in extracts of brain (65.8 pmol/g), small intestine (44.2 pmol/g) and rectum (13.2 pmol/g) of the European common frog (Rana temporaria). No immunoreactivity was detected in extracts of stomach and skin. Reverse-phase HPLC analysis of each tissue extract resolved a single immunoreactive peptide with identical retention time in each case. The immunoreactive peptide was isolated by reverse-phase HPLC from brain extracts and an N-terminal pyroglutamyl residue was successfully removed enzymatically. The molecular mass of des(pyroglutamyl) frog NT, determined by plasma desorption mass spectroscopy, was 1440 Da. The primary structure of this peptide was determined by gas-phase sequencing and the calculated molecular mass, 1440.7 Da, was in close agreement with that derived by mass spectroscopy. The full primary structure of frog NT was established as: QSHISKARRPYIL. When compared with bovine NT, frog NT exhibits five amino acid substitutions in the N-terminal region, whereas the C-terminal hexapeptide sequence (RRPYIL), which mediates the classical biological effects of NT, is completely conserved. Amphibia thus possess a tridecapeptide NT which is analogous to that of higher vertebrates and considerable constraints on the primary structure of the C-terminal biologically-active core have existed for a vast evolutionary time span.
Amino Acid Sequence↗
The primary structure and tissue distribution of an amphibian neuropeptide Y.
Neuropeptide Y (NPY) has been isolated and sequenced from brain extracts of the European common frog, Rana temporaria. Plasma desorption mass spectroscopy of the purified peptide indicated a molecular mass of 4243.3 Da which was in agreement with that deduced from the sequence (4243.7 Da), incorporating a C-terminal amide. The primary structure of frog NPY was established as: YPSKPDNPGEDAPAEDMAKYYSALRHYINLITRQRY-NH2. Frog NPY contains a single, highly-conservative amino acid substitution (Lys for Arg at residue 19) with respect to human NPY. NPY immunoreactivity was localised exclusively in nerves within the brain, pancreas and gastrointestinal tract and reverse-phase HPLC of extracts of these tissues resolved a single immunoreactive peptide of identical retention time in each case. The primary structure of NPY has therefore been highly-conserved over a considerable evolutionary time-span.
Amino Acid Sequence↗
Neuropeptide F-immunoreactivity in the monogenean parasite Diclidophora merlangi.
The localisation and distribution of neuropeptide F (NPF)-immunoreactivity (IR) in the monogenean fish-gill parasite, Diclidophora merlangi, have been investigated by whole-mount immunocytochemistry interfaced with confocal scanning laser microscopy and, at the ultrastructural level, by indirect immunogold labeling. Using antisera directed to intact synthetic NPF (Moniezia expansa, residues 1-39) or to the C-terminal decapeptide (residues 30-39) of synthetic NPF (M. expansa), immunostaining was found throughout the central (CNS) and peripheral nervous systems (PNS), including the innervation of the reproductive system. Immunoreactivity was found to be more intense using the antiserum to the C-terminal decapeptide fragment of NPF. At the subcellular level, gold labeling of NPF-IR was found exclusively over the contents of dense-cored vesicles that occupied nerve axons of both the CNS and the PNS. The distribution pattern of immunostaining for NPF mirrored exactly that previously documented for the vertebrate pancreatic polypeptide (PP) family of peptides and for FMRFamide. This finding and the results of preabsorption experiments strongly suggest that NPF is the predominant native neuropeptide in D. merlangi and that it accounts for most of the immunostaining previously obtained with PP and FMRFamide antisera.
Animals↗
Immunoreactivity to two specific regions of chromogranin A in the nervous system of Ascaris suum: an immunocytochemical study.
Antisera to a highly conserved region of chromogranin A (sequence KELTAE) and to a hexapeptide (sequence KGQELE) adjacent to the putative C-terminus of pancreastatin, a peptide whose sequence is found within the chromogranin A molecule, have been used to examine the localisation of immunoreactivity (IR) to these peptides in Ascaris suum. IR to both peptides was found in the nerve rings and nerve cords. In addition, KGQELE-IR was also observed in the pharyngeal neurones and in a network of fibres on the surface of the female gonoduct. The staining was specific in that it could be abolished by preincubation of the antisera with the appropriate antigen. The two antisera appeared to be staining different subsets of neurones, suggesting that (at least) two peptides were being recognised. The wide-spread distribution of IR to both peptides throughout the nervous system of the parasite suggests that the peptides carrying the epitopes recognised by the antisera are of fundamental importance to the functioning of the parasite's nervous system.
Amino Acid Sequence↗
Characterization and localization of glutathione binding sites on cultured astrocytes.
Glutathione (GSH) binding sites found in brain white matter in a previous study using biotinylated GSH (Third IBRO World Congress Neurosci. Abstr., 1991, P59.17) suggested that there might GSH receptors on glial cells. In the present study, radioligand receptor assays were performed on cultured astrocytes using [35S]GSH. Scatchard analyses of saturation binding of [35S]GSH revealed two binding sites: Kd1 = 2.0 +/- 0.1 nM, Bmax1 = 89.5 +/- 1.5 fmole/2.2 x 10(5) cells and Kd2 = 12.8 +/- 0.4 nM, Bmax2 = 187.7 +/- 2.4 fmol/2.2 x 10(5) cells. The saturable and displacible high affinity [35S]GSH binding we have observed suggests that this binding is not due to GSH sequestration by uptake sites or to the association of GSH with GSH S-transferases or GSH peroxidases which have Kds in the microM range. Colloidal gold and immunofluorescence double labelling were used to visualize the binding sites at the cellular level. Positive colloidal gold decoration further suggests that these labelled binding sites are membrane receptors on astrocytes.
Animals↗
Characterization and regulation of a high affinity [3H]CNQX labelled AMPA receptor in rat neocortex.
We have characterized a high affinity site of the alpha-amino-3 hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor in in vitro living slices of adult rat neocortex using [3H]CNQX, and AMPA antagonist. [3H]CNQX labelled multiple binding sites with a Bmax of a high affinity site of approximately 470 fmol/mg protein and an apparent Kd of 11.3 nM. The high affinity site of the AMPA receptor could be down-regulated (36%) by 2 h preincubations in quisqualate, an AMPA agonist. Increases in electrical activity induced by a combination of veratridine and glutamate also led to an average decrease of the high affinity AMPA receptor number of 17%. In addition, preincubations with muscimol, a GABAA agonist, as well as glutamate agonists kainate and N-methyl-D-aspartate (NMDA) led to an average increase in high affinity AMPA receptor number of 17%, 14%, and 37%, respectively. The present results show that a ligand-gated high affinity AMPA receptor can be regulated by agonist stimulation as well as changes in neural activity.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Age-dependent regulation of GABAA receptors in neocortex.
We have shown previously that GABAA receptors labelled with the antagonist [3H]SR95531 can be regulated in a living cortical slice preparation by agonists or changes in electrical activity. Due to the important role that receptor regulation may play in controlling neural activity, we have now investigated the regulation of GABAA receptors in neocortex at different stages in postnatal life. We found that regulation by agonist stimulation and increases in bioelectric activity is age-dependent in amount and, in the latter case, in direction. Using muscimol as an agonist we observed a GABAA receptor down-regulation of between 60 and 70% at 20-30 days of age; in adults muscimol gave an 11% down-regulation. A combination of veratridine and glutamate gave a peak down-regulation of 39% at 20 days postnatal, but an up-regulation of 58% in adults. These age-dependent effects may signal a role for receptor regulation in cortical neural critical period plasticity.
Aging↗