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P Thompson

Publications and source records attributed to P Thompson.

At least 55 records · Page 3Linked to original sources

Evidence for the activation of PAR-2 by the sperm protease, acrosin: expression of the receptor on oocytes.

Proteinase-activated receptor-2 (PAR-2) is a member of a family of G-protein-coupled, seven-transmembrane domain receptors that are activated by proteolytic cleavage. The receptor is expressed in a number of different tissues and potential physiological activators identified thus far include trypsin and mast cell tryptase. Acrosin, a trypsin-like serine proteinase found in spermatozoa of all mammals, was found to cleave a model peptide fluorescent quenched substrate representing the cleavage site of PAR-2. This substrate was cleaved with kinetics similar to those of the known PAR-2 activators, trypsin and mast cell tryptase. Acrosin was also shown to induce significant intracellular calcium responses in Chinese hamster ovary cells stably expressing intact human PAR-2, most probably due to activation of the receptor. Immunohistochemical studies using PAR-2 specific antibodies indicated that the receptor is expressed by mouse oocytes, which suggests that acrosin may play additional role(s) in the fertilization process via the activation of PAR-2 on oocytes.

Acrosin↗

Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies.

OBJECTIVE: To determine the validity of a clinical diagnosis of probable or possible dementia with Lewy bodies (DLB) made using International Consensus criteria. BACKGROUND: Validation studies based on retrospective chart reviews of autopsy-confirmed cases have suggested that diagnostic specificity for DLB is acceptable but case detection rates as low as 0.22 have been suggested. METHODS: We evaluated the first 50 cases reaching neuropathologic autopsy in a cohort to which Consensus clinical diagnostic criteria for DLB, National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for vascular dementia (VaD) had been prospectively applied. RESULTS: Twenty-six clinical diagnoses of DLB, 19 of AD, and 5 of VaD were made. At autopsy, 29 DLB cases, 15 AD, 5 VaD, and 1 progressive supranuclear palsy were identified. The sensitivity and specificity of a clinical diagnosis of probable DLB in this sample were 0.83 and 0.95. Of the five cases receiving a false-negative diagnosis of DLB, significant fluctuation was present in four but visual hallucinations and spontaneous motor features of parkinsonism were generally absent. Thirty-one percent of the DLB cases had additional vascular pathology and in two cases this contributed to a misdiagnosis of VaD. No correlations were found between the distribution of Lewy bodies and clinical features. CONCLUSION: The Consensus criteria for DLB performed as well in this prospective study as those for AD and VaD, with a diagnostic sensitivity substantially higher than that reported by previous retrospective studies. DLB occurs in the absence of extrapyramidal features and in the presence of comorbid cerebrovascular disease. Fluctuation is an important diagnostic indicator, reliable measures of which need to be developed further.

Aged↗

Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: implications for the tertiary structure of the receptor and for an N-terminal binding site for HIV-1 gp120.

The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9 / 1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7 / 1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9 / 1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7 / 1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.

Amino Acid Sequence↗

Functional outcome and satisfaction after photorefractive keratectomy. Part 2: survey of 690 patients.

PURPOSE: To document patient satisfaction and self-perceived quality of vision after bilateral photorefractive keratectomy (PRK). DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Consecutive patients who underwent bilateral PRK from May 1994 through May 1997 by the 12 surgeons of four collaborating centers with a minimum of 4 months since the last surgery and up to 30 months since the first surgery. METHODS: A questionnaire with known psychometric properties was self-administered by the patients. MAIN OUTCOME MEASURES: Responses to individual questions and scale scores. RESULTS: A total of 929 questionnaires were sent, of which 690 were answered and returned (74.3% response rate). The preoperative spherical equivalent ranged from -0.38 diopters [D] to -27.75 D (mean, -5.32 D; standard deviation, 2.85 D). Although 91.8% of the patients were satisfied or very satisfied with their surgery, 96.3% considered that their main goal had been reached, and 95.7% would still choose to have surgery if they had it to do over. The degree of satisfaction was proportional to the postoperative uncorrected visual acuity in the best eye expressed in LogMAR (r = -0.18, P: = 0. 0001) and was negatively correlated with the importance of the corneal haze (r = -0.23, P = 0.0001). Daytime glare was reported to be greater than before surgery by 55.1% of patients. A decrease in night vision was reported by 31.7% of patients, and 31.1% of patients reported increased difficulty driving at night because of their vision. CONCLUSIONS: Overall satisfaction after PRK for low to severe myopia appears to be very good. Glare and night vision disturbance, particularly bothersome for night driving, seem to constitute significant secondary effects that deserve further investigation and should be kept in mind for future improvements in the technique.

Adolescent↗

Acular as a single agent for use as an antimiotic and anti-inflammatory in cataract surgery.

PURPOSE: To assess the safety and effectiveness of ketorolac tromethamine 0. 5% (Acular) as a cost-efficient single agent to prevent intraoperative miosis and postoperative inflammation in cataract surgery. METHODS: Both eyes of 26 patients were randomized to receive Acular preoperatively and postoperatively or flurbiprofen sodium (Ocufen) preoperatively and prednisolone acetate 1% (Pred Forte) postoperatively. Time scheduled between procedures was from 2 weeks to 1 month. Pupil dilation was measured preoperatively, intraoperatively, and at the end of surgery. Cell and flare were measured 1 day, 1 week, and 1 month postoperatively. RESULTS: A comparison of the Acular and the Ocufen/Pred Forte groups (n=22) showed no statistically significant differences in dilation (preoperative versus postpostoperative) or cell and flare postoperatively. CONCLUSIONS: Using Acular as a single agent was as effective as the combination of preoperative Ocufen and postoperative Pred Forte in preventing intraoperative miosis and postoperative inflammation in cataract surgery. The use of Acular as a single agent could save the expense of using separate anti-inflammatory and antimiotic preparations preoperatively and postoperatively, enhancing convenience for the surgeon and surgical facility.

Anterior Chamber↗

Internal biliary stenting in orthotopic liver transplantation.

Biliary complications account for significant morbidity in orthotopic liver transplantation (OLT), with a reported incidence ranging from 6% to 47%, and many centers are reassessing the need and options available for stenting the biliary anastomosis. We report on our experience using a 6F Silastic, double-J, ureteral stent as an internal biliary stent in OLT. From October 15, 1995, to September 30, 1998, a total of 99 patients at our institution underwent 108 OLTs. Of these, 77 patients received an end-to-end choledochocholedochostomy over an internal stent. Three patients died within 1 week post-OLT, leaving 74 patients for evaluation (follow-up, 2 to 38 months). Stents were placed transanastomotic and transsphincteric at the time of OLT and secured with a dissolvable suture. At 4 to 6 weeks post-OLT, stents visible within the biliary tree on kidney, ureters, and bladder radiograph were removed endoscopically. Graft and patient survival rates were 92% and 96%, respectively. There were 12 biliary complications (18%): anastomotic leak in 6 patients (9%), anastomotic stricture in 5 patients (7.6%), and stent migration in 1 patient (1.5%). Thirty-two patients (43%) passed the biliary stent without intervention, whereas 42 patients (57%) underwent esophagogastro duodenoscopy (EGD) stent removal at 4 to 6 weeks without incident. Treatment of the complications included percutaneous drainage, endoscopic dilatation with stenting, and/or conversion to Roux-en-Y choledochojejunostomy. The use of the 6 F Silastic, double-J, ureteral stent provides a safe and effective means of stenting the biliary anastomosis in OLT. Major advantages to this method are that it: (1) is completely internal, (2) is biliary decompressive, (3) is radiopaque, (4) can be spontaneously passed, and (5) is easily accessible for EGD extraction.

Adult↗

Epilepsy and the family: a review of current literature.

Although the negative effect of epilepsy on patient's psychosocial well-being has been increasingly documented in the last decade, the influence of the condition on the family has attracted much less interest. This paper reviews the present state of family research, examining the influence of both childhood and adulthood epilepsy on the psychological and social well-being of family members. Studies indicate that epilepsy may cause high levels of psychosocial difficulties for all family members, including stigmatization, stress, psychiatric morbidity, marital problems, poor self esteem and restriction of social activities. Studies also suggest that the family environment may be an important intervening factor between the condition and the outcome for the family unit, and a number of family factors are reviewed which have been suggested to mediate this relationship, with recommendations being made for their use in intervention studies. Shortcomings of the family studies to date are discussed and these include: concentration on examination of issues around family life, studies being based on reports from single members of the family and the selection of subjects from clinical populations. Recommendations are made concerning methodological and conceptual issues that need addressing for future research.

Adaptation, Psychological↗

The constituent structure of autobiographical memory: autobiographical fluency in people with chronic epilepsy.

A total of 59 people with chronic epilepsy recalled autobiographical episodes and personal facts (such as the names of friends or teachers) from various lifetime periods. Also tested was their verbal fluency and their fluency in generating items from semantic categories (animals, vegetables, US presidents, and British prime ministers). Results of a cluster analysis and a common factor analysis confirmed a dissociation between the retrieval of autobiographical information and that of nonpersonal semantic information. There was a similar dissociation between the recall of personal episodes and the recall of the personal information, but the corresponding factors were highly correlated with one another. Finally, verbal fluency performance was significantly correlated with the retrieval of personal information, personal episodes, and common objects, but not with that of public figures. The constituent structure of autobiographical fluency is extremely robust across different populations.

Adult↗

Evaluation of octree regional spatial normalization method for regional anatomical matching.

The goal of regional spatial normalization is to remove anatomical differences between individual three-dimensional (3D) brain images by warping them to match features of a standard brain atlas. Processing to fit features at the limiting resolution of a 3D MR image volume is computationally intensive, limiting the broad use of full-resolution regional spatial normalization. In Kochunov et al. (1999: Neuro-Image 10:724-737), we proposed a regional spatial normalization algorithm called octree spatial normalization (OSN) that reduces processing time to minutes while targeting the accuracy of previous methods. In the current study, modifications of the OSN algorithm for use in human brain images are described and tested. An automated brain tissue segmentation procedure was adopted to create anatomical templates to drive feature matching in white matter, gray matter, and cerebral-spinal fluid. Three similarity measurement functions (fast-cross correlation (CC), sum-square error, and centroid) were evaluated in a group of six subjects. A combination of fast-CC and centroid was found to provide the best feature matching and speed. Multiple iterations and multiple applications of the OSN algorithm were evaluated to improve fit quality. Two applications of the OSN algorithm with two iterations per application were found to significantly reduce volumetric mismatch (up to six times for lateral ventricle) while keeping processing time under 30 min. The refined version of OSN was tested with anatomical landmarks from several major sulci in a group of nine subjects. Anatomical variability was appreciably reduced for every sulcus investigated, and mean sulcal tracings accurately followed sulcal tracings in the target brain.

Algorithms↗

Cadherin-11 is expressed in invasive breast cancer cell lines.

In several cancers, including breast cancer, loss of E-cadherin expression is correlated with a loss of the epithelial phenotype and with a gain of invasiveness. Cells that have lost E-cadherin expression are either poorly invasive with a rounded phenotype, or highly invasive, with a mesenchymal phenotype. Most cells lacking E-cadherin still retain weak calcium-dependent adhesion, indicating the presence of another cadherin family member. We have now examined the expression of the mesenchymal cadherin, cadherin-11, in breast cancer cell lines. Cadherin-11 mRNA and protein, as well as a variant form, are expressed in the most invasive cell lines but not in any of the noninvasive cell lines. Cadherin-11 is localized to a detergent-soluble pool and is associated with both alpha- and beta-catenin. Immunocytochemistry shows that cadherin-11 is localized to the cell membrane at sites of cell-cell contact as well as at lamellipodia-like projections, which do not interact with other cells. These results suggest that cadherin-11 expression may be well correlated with the invasive phenotype in cancer cells and may serve as a molecular marker for the more aggressive, invasive subset of tumors. Cadherin-11 may mediate the interaction between malignant tumor cells and other cell types that normally express cadherin-11, such as stromal cells or osteoblasts or perhaps even with the surrounding extracellular matrix, thus facilitating tumor cell invasion and metastasis.

Breast Neoplasms↗

Retrograde amnesia: clinical and methodological caveats.

Several clinical and methodological caveats are outlined as they pertain to retrograde amnesia research, and data relevant to these caveats are presented. Three caveats in particular are noted in relation to recently published cases of marked retrograde amnesia; (i) temporal lobe epilepsy may influence memory for news events; (ii) there may be additional, unsuspected pathology in cases of amnesia, such as those with cerebral hypoxia; (iii) degree of media exposure is closely related to performance on the types of news events memory tests that are commonly used in retrograde amnesia research.

Adult↗

Wine-induced asthma: a placebo-controlled assessment of its pathogenesis.

BACKGROUND: The sulfite family of food additives has been implicated in the pathogenesis of wine-induced asthma. However, the evidence supporting this is weak, and because wines have many hundreds of components, nonsulfite-associated mechanisms may also play a role. OBJECTIVES: The aim of the study was to assess the potential sensitivity of persons with asthma to nonsulfite components in wine by using low-sulfite wine challenges. METHODS: Sixteen adults with a strong history of wine-induced asthma were challenged with both low-sulfite red and white wines and wine-placebo drinks. Challenges were performed double blind, using a Latin square design, with lung function being assessed before the challenge and at 5, 10, 15, 30, and 60 minutes after the challenge. Subsequently, single-blind challenges with high-sulfite white wine were also completed in 10 individuals whose lack of reactivity to low-sulfite white wine suggested possible reactivity to sulfite additives. RESULTS: The mean FEV1; forced expiratory flow, mid-expiratory phase; and peak expiratory flow of subjects to low-sulfite red and white wines and red and white placebo wines were not significantly different. Furthermore, with a predetermined criterion of a fall in FEV1 of more than 15% representing a positive challenge, only one individual exhibited a positive reaction in the presence of a negative response to placebo. Only 2 of the 10 test individuals who were challenged with a high-sulfite wine demonstrated a marked and rapid fall in FEV1. Reactivity to low-sulfite wines appears to occur only in a small number of individuals who report sensitivity to wines, suggesting that the sulfite additives may be the major cause of wine-induced asthmatic reactions. However, direct challenge with high-sulfite wine revealed only 2 clear reactions in this asthma cohort. CONCLUSION: Wine-induced asthma appears to be a complex phenomenon and may involve several mechanisms that are codependent.

Adult↗

Flaviviridae polymerase and RNA replication.

Sequence motifs within the non-structural protein NS5 or NS5B of the members of the family Flaviviridae suggest that this protein is the RNA-dependent RNA polymerase. This protein has now been expressed in various in vitro systems and used in polymerase assays. To understand the role of the RNA polymerase in RNA replication, this review will examine not only the polymerase protein but also the other proteins in the RNA replication complex. To date, several groups have investigated the interaction of these proteins both in vitro and in vivo and also the interaction of these proteins with the RNA signals at the 3' terminus of the RNA. Infectious clones and replicons containing the non-structural proteins have now been generated and these will be useful tools in understanding the processes of initiation and elongation of both positive and negative RNA synthesis.

Flaviviridae↗

Drug extrusion, 125I- efflux and the control of intracellular [Ca2+] in drug-resistant ovarian epithelial cells.

Experiments were undertaken using an ovarian adenocarcinoma cell line (A2780) and a drug-resistant strain (A2780.ad) derived from this line. P-glycoprotein could not be detected in A2780 cells but was essentially ubiquitous in A2780.ad cells, although removing the selective pressure for drug resistance led to reduced expression. However, the amount of P-glycoprotein present was used to predict the capacity of these cells to extrude rhodamine-123 (R-123) and their resistance to adriamycin, a cytotoxic drug. This accords with the role of P-glycoprotein as a drug pump. Although hypotonic solutions increased anion efflux from A2780 and A2780.ad cells, larger responses occurred in the parental line. Moreover, R-123 extrusion and anion efflux appeared to be mutually independent processes and so these data do not support the view that P-glycoprotein is involved in the control of volume-sensitive anion channels. Hypotonic solutions increased intracellular free calcium ([Ca2+]i) in drug-resistant cells but not in the parental line, and so establishing a drug-resistant strain may affect the control of [Ca2+]i during osmotic swelling. This could account for effects that were previously attributed to P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease.

BACKGROUND: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. METHODS: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. RESULTS: D2 receptors were up-regulated in neuroleptictolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. CONCLUSIONS: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.

Adult↗

Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis.

Gingipain-R, the major arginine-specific proteinase from Porphyromonas gingivalis, a causative agent of adult periodontal disease, was found to cleave a model peptide representing the cleavage site of proteinase-activated receptor-2 (PAR-2), a G-protein-coupled receptor found on the surface of neutrophils. The bacterial proteinase was also shown to induce an increase in the intracellular calcium concentration of enzyme-treated neutrophils, most probably due to PAR-2 activation. This response by neutrophils to gingipain-R may be a mechanism for the development of inflammation associated with periodontal disease.

Adhesins, Bacterial↗