Publications by authors named "Peter J Roberts"

Article Synopsis
  • - The study focused on gastrointestinal stromal tumors (GISTs), which often have mutations in the KIT or PDGFRA proteins, making them targets for the drug imatinib mesylate.
  • - Analysis of tumors from 127 patients revealed that 88.2% had KIT mutations (mostly in exons 9 and 11), with those having exon 11 mutations showing an 83.5% response rate to imatinib, while those with exon 9 mutations or no detectable mutations had lower response rates.
  • - The findings highlight that the presence and type of mutations in KIT or PDGFRA are significant indicators of how well patients with GISTs might respond to imatinib treatment.
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Conservationists speculated on potential benefits to wildlife of lockdown restrictions because of the COVID-19 pandemic but voiced concern that restrictions impeded nature conservation. We assessed the effects of lockdown restrictions on biodiversity conservation in South Africa, a biodiverse country with economic inequality and reliance on wildlife resources. We solicited expert opinion using the IUCN's Threats Classification Scheme to structure a questionnaire and illustrated responses with individual case studies from government parastatal and non-governmental conservation organisations.

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Hippos transfer massive quantities of trophic resources from terrestrial to aquatic ecosystems through defecation. The ramifications of the latter for the functioning of benthic ecosystems are unknown, but are dependent ultimately on rates of utilisation relative to inputs. Low input and high utilisation can strengthen bottom-up pathways and enhance consumer biomass and abundance.

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Aim: To investigate the quality of life following laparoscopic Nissen fundoplication by assessing short-term and long-term outcomes.

Methods: From 1992 to 2005, 249 patients underwent laparoscopic Nissen fundoplication. Short-term outcome data including symptom response, side effects of surgery, endoscopy, and patient's perception of overall success were collected prospectively.

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An algorithm based on Tikhonov regularization in generalized form is described to perform an inverse Laplace transform of multidimensional data without a non-negativity (NN) constraint for spectrum conditioning. Uniform penalty (UP) regularization is used to reduce the requirement for NN, and a further penalty is introduced for zero-crossing (ZC) of the spectrum. This ZC term is weighted with the slope of the curve, which does not prevent negative modes in the spectrum but makes nonphysical undershooting in the vicinity of narrow peaks more expensive.

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Background: Breast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g.

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To investigate the susceptibility of the group II metabotropic glutamate receptor mGlu2 to agonist-induced desensitization, the receptor was stably expressed in Chinese hamster ovary (CHO-mGlu2) or C6 glioma cells (C6-mGlu2). Exposure of CHO-mGlu2 cells to the group II mGlu receptor agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (LCCG-1; 10 μM) for up to 15 h did not affect the subsequent ability of LCCG-1 to inhibit forskolin-stimulated cAMP accumulation. Similarly, in C6-mGlu2 cells, prolonged exposure to LCCG-1 also did not affect the subsequent ability of LCCG-1 to inhibit cAMP formation.

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Adiabatic soliton compression by means of a pressure gradient in a hollow-core photonic bandgap fiber is investigated theoretically and numerically. It is shown that the duration of the compressed pulse is limited mainly by the interplay between third-order dispersion and the Raman-induced soliton frequency shift. Analytical expressions for this limit are derived and compared with results of detailed numerical simulations for a realistic fiber structure.

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Purpose: The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status.

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Strong expression of many matrix metalloproteinases (MMPs) has been related to poor survival of colorectal cancer (CRC) patients. The expression of tissue inhibitors of metalloproteinases (TIMPs) has been associated with both a beneficial and a poor outcome and there is thus a need to further clarify the significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and TIMPs in CRC was evaluated.

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Astrocytes express mainly metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5 receptor subtypes, which show opposing effects on cellular proliferation upon activation. In this study, we investigated the mechanisms by which activation of these receptors modulates astrocyte proliferation. Activation of metabotropic glutamate receptor 5 with (S)-3,5-dihydroxyphenylglycine increased phospholipase D activity in astrocytes as well as astrocyte proliferation.

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Purpose: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem.

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Purpose: Clinicopathologic staging is even today the best prognostic factor in both colon and rectal cancers. There is still considerable variation in survival within the stages. To find other prognostic indicators we investigated six biologic markers associated with apoptosis and cell proliferation.

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The natural product willardiine (8) is an AMPA receptor agonist while 5-iodowillardiine (10) is a selective kainate receptor agonist. In an attempt to produce antagonists of kainate and AMPA receptors analogues of willardiine with substituents at the N3 position of the uracil ring were synthesized. The N3-4-carboxybenzyl substituted analogue (38c) was found to be equipotent at AMPA and GLUK5-containing kainate receptors in the neonatal rat spinal cord.

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The surface expression of G protein-coupled receptors is regulated by internalization. For many receptors, a constitutive level of internalization in the absence of agonist has been reported. The constitutive internalization of metabotropic glutamate receptor 1a (mGluR1a) has been described, but in general little attention has been dedicated to this important aspect of receptor regulation.

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Aim: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.

Methods: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.

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Background And Aims: The effect of surgical training level, experience, and operation volume on complications and survival in colorectal cancer during a 10-year period in a medium-volume university hospital was retrospectively studied.

Patients And Methods: Four hundred and fifty-six patients were resected for primary colorectal adenocarcinoma during the 10-year period of 1981-1990, and of these, 387 patients underwent resection with curative intent. The surgeons were divided into three groups according to training level and volume: group 1, surgeons in training and other surgeons operating annually on only 1-4 patients; group 2, surgeons specializing in gastrointestinal surgery (average annual volume 4-13 operations); group 3, specialists in gastrointestinal surgery (average annual volume 3-8 operations).

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In this study we characterized the heterologous desensitization and internalization of the metabotropic glutamate receptor 1 (mGluR1) splice variants mGluR1a and mGluR1b following activation of endogenous G(q/11)-coupled receptors in HEK293 cells. Agonist activation of M1 muscarinic acetylcholine or P2Y1 purinergic receptors triggered the PKC- and CaMKII-dependent internalization of mGluR1a. In co-immunoprecipitation studies, both glutamate and carbachol increased the association of GRK2 with mGluR1a.

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In this study, we characterized the effects of activation of cyclic AMP-dependent protein kinase (PKA) on the internalization and functional coupling of the metabotropic glutamate receptor (mGluR1) splice variants mGluR1a and mGluR1b. Using an enzyme-linked immunosorbent assay technique to assess receptor internalization, we found that the glutamate-induced internalization of mGluR1a or mGluR1b transiently expressed in human embryonic kidney (HEK) 293 cells was inhibited by coactivation of endogenous beta2-adrenoceptors with isoprenaline or by direct activation of adenylyl cyclase with forskolin. The PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H89) blocked the effects of both isoprenaline and forskolin.

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Three group I mGluR antagonists CPCCOEt, LY367385 and BAY36-7620, were analyzed for their effect on cell surface expression of metabotropic glutamate receptor 1a and 1b. All three antagonists inhibited glutamate-induced internalization of mGluR1a and mGluR1b. However, when added alone, either LY367385 or BAY36-7620 increased the cell surface expression of mGluR1a but not mGluR1b.

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Several excitatory amino acid ligands were found potently to inhibit forskolin-stimulated cAMP accumulation in rat cultured cerebellar astrocytes: L-cysteine sulfinic acid (L-CSA) = L-aspartate > L-glutamate >/= the glutamate uptake inhibitor, L-PDC. This property did not reflect activation of conventional glutamate receptors, since the selective ionotropic glutamate receptor agonists NMDA, AMPA, and kainate, as well as several mGlu receptor agonists [(1S,3R)-ACPD, (S)-DHPG, DCG-IV, L-AP4, L-quisqualate, and L-CCG-I], were without activity. In addition, the mGlu receptor antagonists, L-AP3, (S)-4CPG, Eglu, LY341495, (RS)-CPPG, and (S)-MCPG failed to reverse 30 microM glutamate-mediated inhibitory responses.

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Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST.

Patients And Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA.

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•  Here, the reliability of published fungal nucleic acid sequences is tested by the critical re-evaluation of 206 named sequences obtained from public-access databases. •  Sequences from the ribosomal RNA (rRNA) gene cluster were examined as these are commonly used to establish fungal phylogeny and evolution, and are also increasingly employed in the identification of fungi from nonculture based studies. •  Fifty-one rRNA internal transcribed spacer (ITS) sequences were obtained for species of Amanita, 55 ITS sequences were obtained for species of Phoma and 100 rRNA small subunit sequences were obtained from representative genera of the order Helotiales.

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