Risk factors for acanthamoeba keratitis. Single use disposable contact lenses should cut risk.
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Acanthamoeba Keratitis↗
Biomedical subjects
M Edwards
Publications and source records attributed to M Edwards.
Molecular analysis at the NF1 locus in astrocytic brain tumors.
BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are at increased risk for developing malignant neural crest tumors and juvenile myeloid leukemia. Although the normal allele of the NF1 tumor-suppressor gene is frequently deleted in some of the malignant tumors that arise in patients with NF1, the role of NF1 alterations in the sporadic forms of these cancers is unclear. METHODS: A series of intragenic sequence polymorphisms was used to investigate lymphocyte and tumor DNA samples from 22 adults with high grade malignant gliomas for loss of heterozygosity (LOH) at NF1. In addition, an assay based on the polymerase chain reaction was used to screen these tumors for point mutations at codon 1423. RESULTS: One recurrent anaplastic astrocytoma showed LOH within NF1 but not with a flanking marker located near the gene. Of 21 informative tumors, none showed point mutations affecting codon 1423 of NF1. CONCLUSION: These data suggest that LOH at NF1 is uncommon in sporadic high grade astrocytoma, and codon 1423 is not a "hot spot" for activating point mutations in these tumors.
Adult↗
Constitutional p53 mutations associated with brain tumors in young adults.
Identification of patients at risk for developing brain tumors is important for the development of preventative strategies. Because individuals with germline p53 mutations may be at increased risk, we examined DNA from brain tumor-derived cell lines and malignant and normal nervous system tissue for p53 gene mutations using the single strand conformation polymorphism assay and direct sequencing of polymerase chain reaction-amplified DNA. We found mutations in the p53 gene in eight of 22 adult glioma tissue specimens and germline mutations in two of these eight patients. In contrast, mutation of the p53 gene was not detectable in either 16 glial tumors occurring in children, glial tumor tissue from three unrelated glioblastoma multiforme patients with a familial history of cancer, or in benign meningiomas. One constitutional p53 mutation was a G to T transversion at codon 154, and the second was a C to T transition at codon 256. Both patients with germline mutations developed glioblastoma multiforme before the age of 31, although the median age for glioma patients is above 50. These findings suggest that p53 germline mutations may identify a subset of young adults predisposed to the development of high-grade astrocytic tumors.
Adult↗
The inhumanity of medicine. Audit of doctors and patients' views may help.
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Attitude of Health Personnel↗
Global motion perception: no interaction between the first- and second-order motion pathways.
The experiments reported here address the issue of whether the pathways which extract motion from first-order and second-order spatial patterns remain separate or whether they combine at some higher level in the motion system to form a single pathway. The question is addressed by investigating the interaction of first-order and second-order stimuli in the processing of a global-motion stimulus [a variant of the task introduced by Newsome & Pare (Journal of Neuroscience, 8, 2201-2211, (1988)]. Two experimental procedures were used. The first consisted of determining the effect of the addition of dots of one type (e.g. first order) undergoing purely random motion on the ability to extract the global-motion signal carried by dots of the other type (e.g. second order). The second experimental procedure consisted of determining the effect of maintaining a coherent-motion signal in one type of dot, moving in the opposite direction to the global-motion direction, on the ability to extract the global-motion signal carried by dots of the other type. The dots were matched for their effectiveness in producing a global motion percept and the results for both procedures were the same. First-order dots impaired the ability to extract second-order global-motion, and second-order dots had no effect on first-order global-motion extraction. It is argued that the sensitivity of the second-order global-motion system to the first-order dots is due to the ability of the second-order local-motion detectors to detect these dots. The present results are thus interpreted as indicating that the first-order and second-order motion pathways remain separate up to and including the level in the motion system at which global-motion signals are extracted.
Humans↗
The function of visual search and memory in sequential looking tasks.
UNLABELLED: Eye and head movements were recorded as unrestrained subjects tapped or only looked at nearby targets. Scanning patterns were the same in both tasks: subjects looked at each target before tapping it; visual search had similar speeds and gaze-shift accuracies. Looking, however, took longer and, unlike tapping, benefitted little from practice. Looking speeded up more than tapping when memory load was reduced: memory was more efficient during tapping. CONCLUSION: eye movements made when only looking are different from those made when tapping. Visual search functions as a separate process, incorporated into both tasks: it can be used to improve performance when memory load is heavy.
Eye Movements↗
CHILD syndrome: analysis of abnormal keratinization and ultrastructure.
A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.
Arm↗
The levels of reliability and validity of the Waterlow pressure sore risk calculator.
The Waterlow pressure sore risk calculator is widely used in the UK but has not been found to display high levels of reliability and validity. Few evaluative studies have been carried out in the community. This study aimed to evaluate the Waterlow score when used by district nurses to assess elderly patients. The score was not found to display high levels of reliability, and suffered from a lack of operational definitions within risk categories. In line with other studies, it was found to over-predict pressure sore formation. The findings of this small study suggest that the Waterlow score should not be used as the sole basis for decisions concerning the use of pressure sore prevention resources. High Waterlow scores may be a predictor of ill health in elderly people and this hypothesis requires further examination. The findings also indicate that clarification of the role of risk calculators in general is needed, as many mediating factors appear to affect the ability of a tool to predict pressure sore formation.
Aged↗
Competitive binding of vascular cell adhesion molecule-1 and the HepII/IIICS domain of fibronectin to the integrin alpha 4 beta 1.
The integrin receptor alpha 4 beta 1 binds to two different ligands, the extracellular matrix glycoprotein fibronectin and the endothelial cell surface protein vascular cell adhesion molecule-1 (VCAM-1). Using probes derived from each ligand and a variety of cell adhesion and ligand-receptor binding assays, we have investigated the relationship between the mechanisms of fibronectin and VCAM-1 interaction with alpha 4 beta 1. CS1 peptide, which represents the dominant active site from the HepII/IIICS recognition domain in fibronectin, was found to inhibit VCAM-1-dependent adhesion in three different assays: MOLT-4 T lymphoblastic leukaemia cell attachment to immobilized recombinant soluble VCAM-1 (rsVCAM-1), MOLT-4 cell attachment to monolayers of VCAM-1-transfected COS-1 cells, and A375-SM melanoma cell spreading on immobilized rs VCAM-1. Half-maximal inhibition required CS1 concentrations of 1.7-3.0 mg/ml, some 3-7-fold higher than that needed to autoinhibit adhesion to CS1-IgG conjugate. Using a more sensitive solid-phase receptor-ligand binding assay, CS1 was found to be a potent inhibitor of the binding of rsVCAM-1 to alpha 4 beta 1 (half-maximal inhibition at 13 micrograms/ml). In agreement with cell-based assays, severalfold lower concentrations of CS1 were required to inhibit binding of recombinant HepII/IIICS region of fibronectin (half-maximal inhibition at 3 micrograms/ml). VCAM-1-alpha 4 beta 1 binding was blocked not only by CS1 peptide but also by the recombinant HepII/IIICS region of fibronectin. Kinetic analysis of CS1 inhibition of VCAM-1 binding revealed that it was directly competitive in nature, indicating that VCAM-1 and fibronectin recognize either identical or spatially overlapping binding sites on alpha 4 beta 1. The implications of these results for the future design of VCAM-1 antagonists are discussed.
Amino Acid Sequence↗
Significant improvement to the catalytic properties of aspartate aminotransferase: role of hydrophobic and charged residues in the substrate binding pocket.
The substrate specificity of tyrosine aminotransferase (eTAT) from Escherichia coli has been tested by transferring the critically different residues Leu39, Glu141, and Arg293 into equivalent positions of aspartate aminotransferase (eAAT). These residues are not directly involved in the catalytic process. The single mutant eAAT V39L possesses greater values of kcat/KM not only for tyrosine but also for aspartate and glutamate. In contrast, the double mutant eAAT P141E,A293R and also the triple mutant eAAT V39L,P141E,A293R exhibit smaller changes of kcat/KM. The converse mutants of tyrosine aminotransferase, in which critical residues of eAAT (Val39) and of mitochondrial AAT (Ala39, Val37) were transferred into equivalent positions of eTAT, exhibited generally decreased values of kcat/KM for both dicarboxylic and aromatic substrates. On the basis of the known structures of eAAT and eAAT V39L as well as of a refined model of eTAT, these results indicate that the different substrate specificities of eAAT and eTAT are due to multiple side chain differences and minor rearrangements of the backbone. The generally improved catalytic efficiency of the mutant eAAT V39L appears to be due to an indirect effect, namely, the facilitated closure of the active site upon substrate binding.
Amino Acid Sequence↗
Prolonged intragraft urokinase with a new infusion wire: improved short-term results.
Patients with aged saphenous vein grafts and recurrent symptoms of angina are being seen with increasing frequency [Bourassa: J Am Coll Cardiol 17:1081-1083, 1991]. The treatment of these patients remains a dilemma. Direct balloon angioplasty is frequently complicated by distal embolization and early restenosis [Aureran and Gruentzig: Am J Cardiol 53:953-954, 1984]. There is evidence that thrombus plays a significant role in this occlusive process [Hartmann et al.: J Am Coll Cardiol 18:1517-1523, 1991]. Prolonged intragraft urokinase infusion with a new multiside hole infusion catheter debulks thrombus and permits balloon angioplasty without the usual complications.
Angina Pectoris↗
Growth hormone-releasing activity of hexarelin in humans. A dose-response study.
Hexarelin is a new hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) that stimulates the release of growth hormone both in vitro and in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2.micrograms.kg-1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (Cmax) were 3.9, 26.9, 52.3, 55.0 ng.ml-1 after 0, 0.5, 1 and 2 micrograms.kg-1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0-180) were 0.135, 1.412, 2.918 and 3.695 micrograms.min.ml-1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 microgram.kg-1 for Cmax and AUC0-180, respectively. The corresponding Emaxs were 55.1 ng.ml-1 and 3936 ng.min.ml-1, thus indicating that the effect after the 2 micrograms.kg-1 dose is very close to the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Case report 870. Schneckenbecken dysplasia, possibly a new variant.
We report the case of a newborn with a lethal newborn skeletal dysplasia, in whom skeletal and morphologic findings resembled those in schneckenbecken dysplasia except that the projection of bone from the medial aspect of the iliac bones, resembling the "snail's" head, was absent. This could be accounted for by variability or genetic heterogeneity.
Bone and Bones↗
Global motion perception: interaction of the ON and OFF pathways.
A number of experiments were conducted to investigate the interaction of the ON and OFF pathways in the processing of global-motion signals. The stimulus employed was a variant of that used by Newsome and Pare [(1988) Journal of Neuroscience, 8, 2201-2211] in which a small subset of dots move in a common (global-motion) direction in a field of randomly moving dots. The threshold measure was the number of dots required to move in the global-motion direction for that direction to be detected. We found that: (1) the extraction of a global-motion signal carried by light dots (luminance above the background) was impaired by the addition of dark dots (luminance below the background) which did not carry the signal (noise dots); (2) sub-threshold summation occurs for global-motion signals carried by light and dark dots; and (3) a signal dot which changed luminance polarity (went from light to dark) did not result in a motion signal--either in the global-motion direction or in the opposite direction (reverse apparent motion). From these findings we conclude that the inputs to the motion sensitive cells have matched spatial opponency (the ON and OFF pathways remain separate at this level) but that they then combine to form a single pathway prior to the extraction of the global-motion signal. These findings are contrary to those predicted by models which advocate squaring or full-wave rectification prior to global motion processing.
Contrast Sensitivity↗
Cell systems capable of sustaining phenobarbital induction by CYP2B genes.
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Animals↗
The rationale for the use of risk calculators in pressure sore prevention, and the evidence of the reliability and validity of published scales.
Recent studies have shown an increase in pressure sore prevalence rates. However, methodological inconsistencies and demographic considerations, which include an ageing population, make it difficult to interpret and compare results. A multiplicity of intrinsic and extrinsic factors are thought to be associated with increased risk. The development of risk calculators which incorporate these factors has been an attempt to identify which subjects are most at risk so that equipment and nursing interventions can be allocated appropriately. Since the 1960s there has been a proliferation of risk assessment scales which have not been subjected to rigorous scrutiny of their reliability and validity, and this is held to represent a failure of nursing research. Recent evidence suggests that if critical cut-off points for 'at-risk' vs. 'no risk' are adjusted for particular patient populations the validity of existing scales can be improved. Missing from the literature are research reports of studies carried out in the community. As a result of demographic changes and community care policies, more 'at-risk' patients are likely to be nursed at home. Future research needs to include community studies, and a more systematic approach in general, to the study of the predictive value of existing scales.
Aged↗
Comparison of cycloplegic and noncycloplegic retinoscopy in Chinese pre-school children.
Twenty-seven Hong Kong Chinese children, aged 3 to 5 1/2 years, were recruited in this study to evaluate the relation between refractive error as measured retinoscopically before and after cycloplegia using cyclopentolate 1%. The noncycloplegic spherical refractive error of these children ranged from -0.75 to +2.50 D and approximately 98% of the Hong Kong pre-school children have a manifest spherical error within this range. The cycloplegic refractive error can be approximated by multiplying the spherical component of the manifest error by 1.45 and adding +0.39 D to the product, while keeping the astigmatic power and axis unchanged. Cyclopentolate 1% requires more time to produce mydriasis and cycloplegia in eyes with heavily pigmented irides; however, its final effect on refractive error is apparently independent of iris pigmentation and depends on the amount of spherical refractive error present.
Accommodation, Ocular↗
Refraction referral criteria for Hong Kong Chinese preschool children.
The major types of ametropia and visual problems for Hong Kong Chinese and Caucasian children are different. Consequently, the referral criteria developed for Caucasian children may not be applicable to Hong Kong children. Results of our study suggested that the referral criteria for Hong Kong children should be set as hyperopia of > or = +2.0 D, myopia of > or = 1.0 D, astigmatism of > or = 1.0 D and anisometropia of > or = 1.25 D. Sensitivity using only these criteria for abnormal refraction in identifying children with amblyopia, esotropia, exotropia and subnormal vision (< 6/12) was respectively 100%, 84.6%, 45.2% and 95.7%. The overall sensitivity for the identification of visual problems was 86.1% and the overall specificity was 76%. If a cover test or a Hirschberg test was introduced into the screening battery so that all the strabismic cases were identified. the overall sensitivity would increase to 98.6%.
Amblyopia↗