Showing papers by "Garth J. S. Cooper published in 2000"
TL;DR: While residues 20-29 contribute to the fibrils' beta-sheet core, the flanking C- and N-terminal regions of the hA peptide determine the interactions involved in the formation of higher order coiled polymorphic superstructures.
313 citations
TL;DR: It is shown that some inclusions in Huntington's disease brain tissue possess an amyloids-like structure, suggesting parallels with other amyloid-associated diseases such as Alzheimer's and prion diseases.
99 citations
TL;DR: The results indicate that antioxidant defence is altered in the schizophrenic hippocampus and suggest that segregation distortion, of schizophrenia susceptibility genes, may be a possible causative factor in the high incidence of schizophrenia.
Abstract: Comparative brain proteome analysis is a new strategy to discover proteins and therefore genes whose altered expression may underlie schizophrenia. This strategy does not require an a priori theory of the pathogenesis or the mode of inheritance of schizophrenia. Using proteome analysis we previously compared the hippocampal proteome, that is, those proteins expressed by the hippocampal genome, of seven schizophrenic individuals with the hippocampal proteome of seven control individuals, matched for age and post mortem delay.1 We found 18 proteins that were significantly altered in concentration in the schizophrenic hippocampus (P < 0.05), when compared to control tissue. One of these proteins was characterised, by N-terminal sequencing, as diazepam binding inhibitor whose gene maps to 6q12-q21. Here we characterise a further three of the 18 proteins as: manganese superoxide dismutase, 6q25.3, T-complex protein 1, 6q25.3-q26 and collapsin response mediator protein 2, 8p21. That three of these four characterised proteins should map to the long arm of the same chromosome is significant (P < 0.002) and suggests the importance of chromosome 6q in schizophrenia. These results indicate that antioxidant defence is altered in the schizophrenic hippocampus and suggest that segregation distortion, of schizophrenia susceptibility genes, may be a possible causative factor in the high incidence of schizophrenia. Molecular Psychiatry (2000) 5, 85-90.
82 citations
TL;DR: The results highlight that the estimation of protein can be affected by methodology and by sample composition, and shows that methods must be optimized for a particular application.
40 citations
TL;DR: Amylin-(1---8) has significant anabolic effects in vivo, suggesting that this peptide or analogs of it should be further evaluated as potential therapies for osteoporosis.
Abstract: Amylin increases bone mass when administered systemically to mice. However, because of its size, the full peptide is not an ideal candidate for the therapy of osteoporosis. The fragment, amylin-(1—...
34 citations
TL;DR: Low-dose infusion of adrenomedullin administered to conscious sheep on a low-salt diet clearly antagonized the vasopressor actions of administered angiotensin II while stimulating cardiac output and heart rate.
Abstract: Biologic actions attributed to adrenomedullin include reduction of arterial pressure and suppression of aldosterone secretion. To assess possible in vivo antiangiotensin II actions of adrenomedullin, we examined hemodynamic and adrenal responses to stepped angiotensin II infusions with or without co-infusions of adrenomedullin (33 ng/kg/min) in conscious sheep under controlled conditions of a low sodium intake. Plasma adrenomedullin levels rose during peptide infusions (p < 0.001) to plateau at approximately 15-18 pM. The dose-dependent pressor response (15-20 mm Hg) of angiotensin II was both delayed and markedly attenuated (p = 0.017) by adrenomedullin, which also stimulated heart rate (p < 0.001) and cardiac output (p < 0.001). Adrenomedullin prevented the angiotensin II-induced increase in peripheral resistance (p < 0.001). Plasma aldosterone responses to angiotensin II were variable and were not significantly altered by concomitant adrenomedullin infusion. In conclusion, low-dose infusion of adrenomedullin administered to conscious sheep on a low-salt diet clearly antagonized the vasopressor actions of administered angiotensin II while stimulating cardiac output and heart rate. The data suggest a possible role for adrenomedullin in cardiovascular homeostasis in part through antagonism of the vasopressor action of angiotensin II.
20 citations
Patent•
29 Mar 2000
TL;DR: A method for promoting bone growth in a patient (e.g., a mammal such as a human) is described in this paper, including the step of administering a therapeutically effective amount of adrenomedullin or an adrenomedulin agonist to said patient.
Abstract: A method for promoting bone growth in a patient (e.g., a mammal such as a human) said method including the step of administering a therapeutically effective amount of adrenomedullin or an adrenomedullin agonist to said patient.
14 citations
12 citations
Patent•
19 Jun 2000
TL;DR: In this paper, a peptide secreted by the pancreatic islet β-cell that stimulates insulin secretion, termed preptin, is described and its analogs and their use as medicaments are described.
Abstract: The invention relates to a bioactive mammalian peptide. In particular, it relates to a peptide secreted by the pancreatic islet β-cell that stimulates insulin secretion, termed preptin. Preptin analogs, pharmaceutical compositions which contain preptin or its analogs and their use as medicaments are inter alia also provided.
9 citations
TL;DR: The synthesis of these tritiated analogues provides an alternative chemically stable radiolabeled ligand which may be useful in exploring receptor interactions within the calcitonin peptide family.
4 citations