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A Olson

Publications and source records attributed to A Olson.

At least 19 recordsLinked to original sources
PubMed2006

RNAi Codex: a portal/database for short-hairpin RNA (shRNA) gene-silencing constructs.

Use of RNA interference (RNAi) in forward genetic screens is proliferating. Currently, short-interfering RNAs (siRNAs) and short-hairpin RNAs (shRNAs) are being used to silence genes to tease out functional information. It is becoming easier to harness RNAi to silence specific genes, owing to the development of libraries of readymade shRNA and siRNA gene-silencing constructs by using a variety of sources. RNAi Codex, which consists of a database of shRNA related information and an associated website, has been developed as a portal for publicly available shRNA resources and is accessible at http://codex.cshl.org. RNAi Codex currently holds data from the Hannon-Elledge shRNA library and allows the use of biologist-friendly gene names to access information on shRNA constructs that can silence the gene of interest. It is designed to hold user-contributed annotations and publications for each construct, as and when such data become available. We will describe features of RNAi Codex and explain the use of the tool.

Animals↗
PubMed2003

Consequences of immunogenicity to the therapeutic monoclonal antibodies ReoPro and Remicade.

The clinical consequences of immune antibodies generated to abciximab (ReoPro) and infliximab (Remicade) are described. Abciximab, a chimaeric Fab fragment that binds to the beta3 integrin of the GPIIb/IIIa and alphavbeta3 receptors on human platelets, is approved in the US and Europe for use in percutaneous coronary intervention (PCI) to prevent cardiac ischaemic complications. The effects of induced antibodies upon the safety and efficacy of repeat administration of abciximab have been evaluated in the ReoPro Re-administration Registry Study, in which 5.7% of patients were HACA positive before re-treatment. An interim evaluation of 1000 patients has indicated that re-administration of abciximab can be accomplished in the setting of PCI with an acceptable safety and efficacy profile. Infliximab is a chimaeric IgG1 antibody specific for human TNFalpha, and is approved in the US and Europe for the acute treatment of the signs and symptoms of Crohn's disease and for the chronic treatment of rheumatoid arthritis (RA). The incidence of antibodies to infliximab is reported to be approximately 10%; however, an inverse dose-immunogenicity relationship was observed, indicating that higher doses of infliximab (> or = 3 to 10 mg/kg) could reduce the incidence of immune antibodies. The induction of immune antibodies could also be reduced by concomitant administration of low-dose methotrexate and other immunosuppressant agents. Although antibodies to infliximab appeared to be associated with lower serum infliximab concentrations and a slightly higher incidence of infusion reactions, these immune antibodies were generally not associated with a reduction in clinical efficacy. In addition, the antibodies induced to infliximab are specific for infliximab, and do not cross-react with other currently available therapeutic antibodies.

Abciximab↗
PubMed2001

The effects of case mixing on word recognition: evidence from a PET study.

The early stages of visual word recognition were investigated by scanning participants using PET as they took part in implicit and explicit reading tasks with visually disrupted stimuli. CaSe MiXiNg has been shown in behavioral studies to increase reaction times (RTs) in naming and other word recognition tasks. In this study, we found that during both an implicit (feature detection) task and an explicit word-naming task, mixed-case words compared to same-case words produced increased activation in an area of the right parietal cortex previously associated with visual attention. No effect of case was found in this area for pseudowords or consonant strings. Further, lowering the contrast of the stimuli slowed RTs as much as case mixing, but did not lead to the same increase in right parietal activation. No significant effect of case mixing was observed in left-hemisphere language areas. The results suggest that reading mixed-case words requires increased attentional processing. However, later word recognition processes may be relatively unaffected by the disruption in presentation.

Attention↗
PubMed2001

Children and guns in a well child cohort.

BACKGROUND: The purpose of this study was to estimate the extent of and to identify predictors of preadolescent gun use in a well child cohort with matched parent and child data. METHODS: We analyzed self-report questionnaires from children and their parents using conditional logistic regression models. Questionnaires were given to 3,145 ten- to twelve-year-old children and 3,145 parents enrolled by their pediatricians in a prevention cohort study. RESULTS: Thirty-two percent of the children lived in households with guns. Children and parents generally agreed about the presence of guns in their homes; 17% had access to unlocked guns in their homes; 22% had fired guns. In this preadolescent cohort, firing guns was associated with being male, having guns in the home, having friends who use guns, and initiation of alcohol use. CONCLUSIONS: In this well child cohort, significant numbers of preadolescent, healthy boys in white, middle-class U.S. homes have access to guns, are using guns, and have friends who use guns. These children are also early alcohol adopters. Safety interventions with parents of preadolescents about the risks for accidental injury, death, and suicide due to child gun use may prove beneficial.

Alcohol Drinking↗
PubMed2001

Separating effects of orthographic similarity and contour summation in the identification of masked letter strings.

We separated effects of contour summation and orthographic similarity under masking conditions, by comparing identification with simultaneous and sequentially presented letter strings, which either did or did not overlap spatially. With overlapping simultaneous stimuli, performance was better for strings with similar contours than for strings with the same letters (the orthographic similarity condition). This suggests that contour summation effects were strongest in the condition where stimuli had similar contours. With sequential presentations, performance in the similar contour and the orthographically similar conditions was equated when the stimuli were overlapping. However, effects of contour summation decreased when prime and target letters were spatially displaced, whereas performance in the orthographically similar condition was maintained. We conclude that effects of orthographic similarity can be distinguished from effects of contour summation, under masking conditions.

Female↗
PubMed2000

Differential effects of word length and visual contrast in the fusiform and lingual gyri during reading.

Previous studies have shown differential responses in the fusiform and lingual gyri during reading and suggested that the former is engaged in processing local features of visual stimuli and the latter is engaged in global shape processing. We used positron emission tomography in order to investigate how these regions are modulated by two common variables in reading: word length (three, six and nine letters) and perceptive similarity to the background (high and low contrast). Increasing both word length and visual contrast had a positive monotonic effect on activation in the bilateral fusiform. However, in the lingual gyrus, activation increased with increasing word length but decreased with increasing contrast. On the basis of previous studies, we suggest that (i) increasing word length increases the demands on both local feature and global shape processing, but (ii) increasing visual contrast increases the demands on local feature processing while decreasing the demands on global shape processing.

Brain Mapping↗
PubMed2000

Fractionating the binding process: neuropsychological evidence distinguishing binding of form from binding of surface features.

We present neuropsychological evidence demonstrating that the binding of form elements into shapes dissociates from the binding of surface detail to shape. Data are reported from a patient with bilateral parietal lesions, GK, who manifests left-side visual extinction along with many illusory conjunctions when asked to discriminate both surface and form information about stimuli. We show that there are effects of grouping on both extinction and illusory conjunctions when the tasks require report of object shape. In contrast, illusory conjunctions involving surface and form information were unaffected by grouping based on shape. In addition, grouping was stronger when forms were presented within the same hemifield than when they appeared in different hemifields, whilst illusory conjunctions of form and colour occurred equally often within and across hemifields. These results support a two-stage account of visual binding: form elements are first bound together locally into shapes, and this is followed by a second stage of binding in which shapes are integrated with surface details. The second but not the first stage of binding is impaired in this patient.

Color Perception↗
PubMed2000

Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica.

OBJECTIVE: To examine the localisation of monocyte chemoattractant protein 1 (MCP-1) in the inflamed vessel wall in temporal arteritis (TA) and to measure MCP-1 in plasma both in patients with TA and patients with polymyalgia rheumatica (PMR). METHODS: By immunohistochemical techniques MCP-1 was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised to the majority of mononuclear cells, some smooth muscle cells, and giant cells in the arterial biopsy specimens from 12 patients with histologically verified TA. In all sections, including the vasa vasorum, the endothelium stained positive. In the intima 73% (range 57-91%), in the media 49% (range 32-67%), and in the adventitia 74% (range of 62-91%) of all cells stained positive. In plasma MCP-1 was significantly raised in untreated TA (n=33) and untreated PMR (n=27) compared with healthy controls (n=12). Untreated TA plasma levels of MCP-1 (mean 391 pg/ml (range 82-778 pg/ml)) were similar to untreated PMR plasma levels (mean 402 pg/ml (range 29-1153 pg/ml)), and no significant difference was found between the two groups of patients. In both patients with TA and patients with PMR no correlation was found between the plasma level of MCP-1 and the erythrocyte sedimentation rate, haemoglobin concentration, and CD4/CD8 ratio. CONCLUSIONS: These results show that MCP-1 plays a part in the disease processes of TA and PMR.

Adult↗
PubMed1999

Importance of factor VIIa Gla-domain residue Arg-36 for recognition of the macromolecular substrate factor X Gla-domain.

Macromolecular substrate docking with coagulation enzyme-cofactor complexes involves multiple contacts distant from the enzyme's catalytic cleft. Here we characterize the binding of the Gla-domain of macromolecular substrate coagulation factor X to the complex of tissue factor (TF) and VIIa. Site-directed mutagenesis of charged residue side chains in the VIIa Gla-domain identified Arg-36 as being important for macromolecular substrate docking. Ala substitution for Arg-36 resulted in an increased KM and a decreased rate of X activation. X with a truncated Gla-domain was activated by mutant and wild-type VIIa at indistinguishable rates, demonstrating that Arg-36 interactions require a properly folded Gla-domain of the macromolecular substrate. VIIa Arg-36 was also required for effective docking of the X Gla-domain in the absence of phospholipid, demonstrating that the Gla-domain of VIIa participates in protein-protein interactions with X. In the absence of TF, the mutant VIIa had essentially normal function, indicating that the cofactor positions VIIa's Gla-domain for optimal macromolecular substrate docking. Computational docking suggests multiple charge complementary contacts of the X Gla-domain with TF.VIIa. A prominent interaction is made by the functionally important X residue Gla-14 with the center of the extended docking site created by residues in the carboxyl module of TF and the contiguous VIIa Gla-domain. These data demonstrate the functional importance of interactions of the Gla-domains of enzyme and substrate, and begin to elucidate the molecular details of the ternary TF.VIIa.X complex.

1-Carboxyglutamic Acid↗
PubMed1999

Guideline for the management of pediatric idiopathic constipation and soiling. Multidisciplinary team from the University of Michigan Medical Center in Ann Arbor.

OBJECTIVE: To develop an evidence-based guideline for the primary pediatric care of children (birth to 18 years old) with idiopathic constipation and soiling. DATA SOURCES: References were identified through a MEDLINE search from January 1975 through January 1998 to address 3 focus questions: (1) the best path to early, accurate diagnosis; (2) best methods for adequate clean-out; and (3) best approaches to promote patient and family compliance with management. DATA SELECTION: Twenty-five references were identified. DATA EXTRACTION: References were reviewed by a multidisciplinary team and graded according to the following criteria: randomized controlled trial; controlled trial, no randomization; observational study; and expert opinion. Evidence tables were developed for each focus question. DATA SYNTHESIS: An algorithm and clinical care guideline were developed by consultation and consensus among team members. Emphasis was placed on methods to promote early identification of pediatric idiopathic constipation and soiling, to recognize points of referral, and to increase patient and family compliance with treatment through use of education, developmentally based interventions, and variables for tracking success of management. CONCLUSION: An algorithm and guideline for pediatric idiopathic constipation and soiling are presented for use by primary care physicians.

Child↗
PubMed1999

Systematic analysis of deficits in visual attention.

A variety of impairments in visual attention can follow damage to the brain. The authors develop systematic methods for analyzing such impairments in terms of C. Bundesen's (1990) Theory of Visual Attention and apply these in a group of 9 patients with parietal lobe lesions and variable spatial neglect. In whole report, patients report letters from brief, vertical arrays in left or right visual field. The results show substantial, largely bilateral impairments in processing capacity, implying a major nonlateralized aspect to neglect. In partial report, arrays contain 1 or 2 letters in red and/or green. The task is to report only those letters in a specified target color. In addition to the expected bias against left-sided letters, patients show striking, bilateral preservation of top-down control, or attentional priority for targets. The results show how differentiation of attentional impairments can be informed by a theory of normal function.

Aged↗
PubMed1999

Developmental surface dysgraphia: what is the underlying cognitive impairment?

The purpose of this study was to investigate the cognitive causes underlying spelling difficulties in a case of developmental surface dysgraphia, AW. Our results do not support a number of possibilities that could be the cause of AW's poor orthographic lexicon, including difficulties in phonological processing, phonological short-term memory, configurational visual memory, and lexical semantic memory. We have found instead that AW performs poorly in tasks that involve detection of the order of adjacent letters in a word or the order of adjacent units in strings of consonants or symbols. Finally, he performs poorly in tasks that involve reconstructing the order of a series of complex visual characters (Japanese and Hindi characters) especially when these are presented sequentially. We advance the hypothesis that AW's poor spelling and good reading skills stem from an underlying pattern of cognitive abilities where a very good visual configurational memory is coupled with a poor ability to encode serial order. This may have resulted in a holistic word-based reading strategy, which, together with the original problem of encoding order, may have had detrimental effects for the acquisition of spelling.

Adult↗
PubMed1998

The expression of MDP-1, a component of Drosophila embryonic basement membranes, is modulated by apoptotic cell death.

Using a novel monoclonal antibody we have studied the expression of a large proteoglycan-type molecule in Drosophila embryos. This molecule is secreted exclusively by migratory, embryonic hemocytes/macrophages and was therefore named MDP-1 for Macrophage-Derived Proteoglycan-1. Expression of MDP-1 begins late during hemocyte differentiation, after these cells have left their birthplace in the head mesoderm. At this time, macrophages are engaged in extracellular matrix deposition and the phagocytosis of cell debris generated by apoptotic events in various parts of the embryo, in particular from the developing central nervous system. Embryos deficient for programmed cell death display a greatly reduced amount of MDP-1 deposition in tissues that normally undergo morphogenetic cell death. This suggests a regulatory role for apoptosis in the terminal differentiation of Drosophila hemocytes. MDP-1 is initially deposited around the developing central nervous system and is later found in basement membrane structures surrounding various other organs, such as the gut, Malpighian tubules and part of the tracheal system. The temporal and localized deposition of MDP-1 suggests that it may play a role in delineating the central nervous system structure during axonogenesis and may participate in the formation of a functional 'blood-brain barrier' in Drosophila.

Animals↗
PubMed1997

Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor.

Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases.

Asparagine↗
PubMed1997

Disruption to word or letter processing? The origins of case-mixing effects.

MiXeD-cAsE stimuli have long been used to test whether word recognition is based on holistic visual information or preliminary letter identification. However, without knowing which properties of mixed-case stimuli disrupt processing, it is not possible to determine which visual units mediate word recognition. The present studies examined the effects of case mixing on word and nonword naming as a function of (a) whether spaces were inserted between letters and (b) whether letter size was alternated independent of letter case. The results suggest that case-mixing disruption effects are due to at least 2 factors: the introduction of inappropriate grouping between letters with the same size and case, and the disruption of transletter features. The data support a model of visual lexical access based on the input from multiple visually based units.

Adult↗
PubMed1996

Molecular docking programs successfully predict the binding of a beta-lactamase inhibitory protein to TEM-1 beta-lactamase.

Crystallization of the 1:1 molecular complex between the beta-lactamase TEM-1 and the beta-lactamase inhibitory protein BLIP has provided an opportunity to put a stringent test on current protein-docking algorithms. Prior to the successful determination of the structure of the complex, nine laboratory groups were given the refined atomic coordinates of each of the native molecules. Other than the fact that BLIP is an effective inhibitor of a number of beta-lactamase enzymes (KI for TEM-1 approximately 100 pM) no other biochemical or structural data were available to assist the practitioners in their molecular docking. In addition, it was not known whether the molecules underwent conformational changes upon association or whether the inhibition was competitive or non-competitive. All six of the groups that accepted the challenge correctly predicted the general mode of association of BLIP and TEM-1.

Amino Acid Sequence↗