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Showing papers by "University of Leicester published in 1994"



Journal ArticleDOI
TL;DR: The EORTC QLQ-LC13 as discussed by the authors is a 13-item questionnaire for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core QoS questionnaire, which covers general aspects of health-related QoS, and (2) additional disease- or treatment-specific questionnaire modules.

726 citations


Journal ArticleDOI
TL;DR: In this article, a simple model was proposed for the thermodynamics of hydration of ions with charges varying from ± 1 to ± 4, depending only on z and their radii r, when taken as spheres.

699 citations


Journal ArticleDOI
TL;DR: At MS32, high frequency mutation processes in sperm appear to be largely germline specific and to occur at a constant rate irrespective of allele size, which implies that germline instability is controlled by elements outside the tandem repeat array.
Abstract: Mutation at the human minisatellites MS32, MS205 and MS31A has been investigated by characterizing mutant alleles in pedigrees and in the case of MS32 by direct analysis of mutant molecules in single sperm. Most mutations at all three loci are polar, involving the preferential gain of a few repeat units at one end of the tandem repeat array. Incoming repeats can be derived from the same allele or the homologous chromosome, through they are frequently rearranged during mutation. Lack of exchange of flanking markers suggests the involvement of complex conversion-like events in the generation of mutant alleles. At MS32, high frequency mutation processes in sperm appear to be largely germline specific and to occur at a constant rate irrespective of allele size. Together with mutational polarity, this implies that germline instability is controlled by elements outside the tandem repeat array.

494 citations


Journal ArticleDOI
TL;DR: In this article, a framework for the development and analysis of robust observers for uncertain dynamical systems is proposed, where a variable structure system approach is used to deal with the numerical tractability of the associated synthesis procedure.
Abstract: A framework is proposed for the development and analysis of robust observers for uncertain dynamical systems. A variable structure systems approach is used. Emphasis is placed upon the numerical tractability of the associated synthesis procedure. A selected numerical example is used to illustrate the proposed algorithm.

444 citations


Journal Article
Sally J Singh1, Morgan, A E Hardman, C Rowe, PA Bardsley 
TL;DR: It is concluded that the shuttle walking test is a valid field exercise test of functional capacity, and relates strongly to VO2max, the traditional indicator of cardiorespiratory capacity.
Abstract: The purpose of this study was to investigate the relationship between performance on the shuttle walking test and maximal oxygen uptake (VO2max) during a conventional treadmill test in patients with chronic airflow limitation. Two different techniques were used to measure oxygen consumption, i.e. conventional Douglas bag techniques (treadmill test) and a portable oxygen consumption meter (shuttle test). Initially, 19 patients performed a shuttle walking test (after one practice walk) and a maximal treadmill walking test, in a randomized, balanced design. Subsequently, 10 patients, (after one practice) completed an unencumbered shuttle walking test and one supporting the portable oxygen consumption meter, in random order. The results of the first experiment revealed a strong relationship between performance during the shuttle walking test and VO2max during the treadmill walking test (r = 0.88). The results of the second experiment consistently demonstrated an incremental increase in oxygen consumption and ventilation in response to the increasing intensity of the shuttle walking test. Again, a strong relationship between VO2max and performance on the shuttle test was demonstrated (r = 0.81). We concluded that the shuttle walking test is a valid field exercise test of functional capacity. Performance on the test relates strongly to VO2max, the traditional indicator of cardiorespiratory capacity.

390 citations


Journal ArticleDOI
TL;DR: The use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species is anticipated.
Abstract: We have isolated short tandem repeat arrays from the human genome, using a rapid method involving filter hybridization to enrich for tri- or tetranucleotide tandem repeats. About 30% of clones from the enriched library cross-hybridize with probes containing trimeric or tetrameric tandem arrays, facilitating the rapid isolation of large numbers of clones. In an initial analysis of 54 clones, 46 different tandem arrays were identified. Analysis of these tandem repeat loci by PCR showed that 24 were polymorphic in length; substantially higher levels of polymorphism were displayed by the tetrameric repeat loci isolated than by the trimeric repeats. Primary mapping of these loci by linkage analysis showed that they derive from 17 chromosomes, including the X chromosome. We anticipate the use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species.

386 citations


Journal ArticleDOI
TL;DR: An in vitro brainstem slice preparation of the superior olivary complex has been developed permitting patch recording from a presynaptic terminal and from its postsynaptic target‐‐the principal neurone of the medial nucleus of the trapezoid body, and whole‐cell recording from the MNTB neurone shows evoked EPSCs preceded by a prespike.
Abstract: 1. An in vitro brainstem slice preparation of the superior olivary complex has been developed permitting patch recording from a presynaptic terminal (calyx of Held) and from its postsynaptic target--the principal neurone of the medial nucleus of the trapezoid body (MNTB). 2. The fluorescent stain DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) was used in fixed tissue and Lucifer Yellow in living slices, to identify calices enclosing single MNTB neuronal somata. 3. Whole-cell recording from the MNTB neurone shows evoked EPSCs preceded by a prespike, corresponding to the presynaptic action potential (AP). In some cases one patch pipette recorded from both pre- and postsynaptic elements, but confirmation of exclusively presynaptic recording was obtained using pipettes containing Lucifer Yellow in a further eleven cases. 4. Under current clamp, the pre- and postsynaptic sites could be distinguished by their response to step depolarizations; presynaptic terminals generated a train of APs at frequencies up to 200 Hz, while MNTB neurones gave a single AP. Each presynaptic AP had an after-hyperpolarization lasting less than 2 ms. 5. Under voltage clamp, step depolarizations of presynaptic terminals generated a tetrodotoxin-sensitive inward current followed by rapidly activating outward potassium currents at potentials more positive than -60 mV. The outward current exhibited little inactivation over the 150 ms steps and 4-aminopyridine (200 microM) blocked 63.0 +/- 14.5% (mean +/- S.D., n = 3) of the sustained current at 0 mV. Like the squid giant synapse, mammalian terminals express rapidly activating 'delayed rectifier'-type potassium currents.

366 citations


Journal ArticleDOI
TL;DR: The binding site for protein G on Fab is relatively invariant across different species and gamma chain subclasses, providing an explanation for the widespread recognition of Fab fragments from mouse and human antibodies by protein G.

350 citations


Journal ArticleDOI
01 Oct 1994-Nature
TL;DR: An exceptionally high proportion of extra-pair paternity is found in a wild population of reed buntings using single-locus DNA fingerprinting and it is proposed that males can assess their likelihood of paternity and adjust their nestling provisioning rates accordingly.
Abstract: EXTRA-PAIR copulations, in which a female copulates with a male other than her mate, are known to occur in many bird species1. Here we study a wild population of reed buntings, Emberiza schoeniclus, using single-locus DNA fingerprinting2,3 and find an exceptionally high proportion of extra-pair paternity that accounts for 55% (118/216) of young and 86% (50/58) of nests. Twelve pairs each raised two broods in a single season in which the proportion of extra-pair young differed between the two broods. A highly significant relationship between a male's parental investment and his degree of paternity was revealed by a comparison between the first and second brood of each pair, with more paternal care usually being provided at the nest that contained a lower proportion of extra-pair young. We propose that males can assess their likelihood of paternity and adjust their nestling provisioning rates accordingly.

345 citations


Journal ArticleDOI
TL;DR: The evidence indicates that phytochrome A plays a role in seed germination, in the control of elongation growth of light-grown seedlings, and in the perception of daylength.
Abstract: Several aspects of the photophysiology of wild-type Arabidopsis thaliana seedlings were compared with those of a phytochrome A null mutant, phyA-1, and a mutant, fhy1, that is putatively involved in the transduction of light signals from phytochrome A. Although phyA seedlings display a near wild-type phenotype when grown in white light (W), they nevertheless display several photomorphogenic abnormalities. Thus, whereas the germination of wild-type and fhy1 seeds is almost fully promoted by a pulse of red light (R) or by continuous far-red light (FR), phyA seed germination is responsive only to R. Following growth under day/night cycles, but not under continuous W, the hypocotyls of light-grown phyA and fhy1 seedlings are more elongated than those of wild-type seedlings. For seedlings grown under low red/far-red (R/FR) ratio light conditions, phyA and fhy1 seedlings display a more marked promotion of hypocotyl elongation than wild-type seedlings. Similarly, seedlings that are doubly null for phytochrome A and phytochrome B(phyA phyB) also have more elongated hypocotyls under low R/FR ratio conditions than phyB seedlings. This indicates that phytochrome A action in light-grown seedlings is antagonistic to the action of phytochrome B. Although wild-type, fhy1, and phyA seedlings flower at essentially the same time under both short-day and long-day conditions, an obvious consequence of phytochrome A deficiency is a pronounced late flowering under conditions where a short day of 8 h of fluorescent W is extended by 8 h of low-fluence-rate incandescent light. The evidence thus indicates that phytochrome A plays a role in seed germination, in the control of elongation growth of light-grown seedlings, and in the perception of daylength.

Journal ArticleDOI
TL;DR: In this paper, the trace element composition of orogenic igneous rocks, with specific reference to granitoids, and in relation to tectonothermal models of subduction zones, is reviewed.
Abstract: Some of the more important constraints on crustal growth mechanisms are reviewed in relation to the trace element composition of orogenic igneous rocks, with specific reference to granitoids, and in relation to tectonothermal models of subduction zones. The wide range of magma types associated with subduction zones is difficult to explain by a single magma-generating mechanism. This variation can be accommodated if some lavas ( are tholeiites and boninites) are formed through wet melting of upwelling asthenosphere at the initiation of oceanic subduction, whereas others are generated from the mantle wedge during the more mature stage of ares, with either hornblende or phlogopite dominated assemblages, where induced convection in the mantle wedge enables source replenishment. Yet other products are generated through melting of the slab (±subducted sediment), but only where the subducting ocean crust is very young and/or warm. The range and variation of trace-element patterns displayed by basic lavas is also prevalent in more siliceous compositions, implying that the mantle component in many granitoids may be much higher than is commonly assumed. As well as the traditional I-type, S-type and A-type granites with generally low-Ba and low-Sr characteristics, there is another important group of granitoids that has high-Ba and high-Sr concentrations, and that consistently has about 10 trace-element characteristics that are complementary in nature to the first groups. This type of granitoid is common in the Arehaean, rare in the Proterozoic, but is surprisingly abundant amongst post-Cretaceous to Recent orogenic volcanic and plutonic rocks. Trace element patterns may be inherited from mineralogically-controlled element fractionation occurring deep in the lithosphere; major element characteristics are more dependent on mineral-fluid control during magma generation.

Journal ArticleDOI
TL;DR: The nitrogen mustards are bifunctional alkylating agents which, although used extensively in cancer chemotherapy, are themselves highly carcinogenic, and no single lesion has been implicated as being primarily responsible for mustard-induced mutagenesis.
Abstract: The nitrogen mustards are bifunctional alkylating agents which, although used extensively in cancer chemotherapy, are themselves highly carcinogenic. All nitrogen mustards induce monofunctional guanine-N7 adducts, as well as interstrand N7-N7 crosslinks involving the two guanines in GNC.GNC (5'-->3'/5'-->3') sequences. In addition, the aromatic mustards melphalan and chlorambucil also induce substantial alkylation at adenine N3, while cyclophosphamide forms phosphotriesters with relatively high frequency. Nitrogen mustards are genotoxic in virtually every assay, and produce a wide array of mutations, including base substitutions at both G.C and A.T base pairs, intragenic as well as multilocus deletions, and chromosomal rearrangements. Mutational spectra generated by these agents in various model systems vary widely, and no single lesion has been implicated as being primarily responsible for mustard-induced mutagenesis. On the contrary, adducts of both adenine and guanine, and monofunctional as well as bifunctional adducts, appear to be involved. Further, it is still not known which types of mutation are responsible for mustard-induced cancers, since no genes have yet been identified which are consistently altered in these malignancies.

Journal ArticleDOI
01 Apr 1994
TL;DR: In this review, Richard Eglen and colleagues discuss recent data concerning the possible role(s) of muscarinic receptor subtypes in smooth muscle and appraise the pharmacological methods for dissecting the function of mus carinic receptorSubtypes in tissues co-expressing multiple receptors.
Abstract: Muscarinic acetylcholine M2 and M3 receptor subtypes are coexpressed in many types of smooth muscle including gastrointestinal smooth muscle, urinary bladder and vascular and airway tissue. Activation of M3 receptors, via the G protein Gq, results in increased polyphosphoinositide hydrolysis, release of Ca2+ ions from the sarcoplasmic reticulum and consequently causes contraction. Quantitation of the relative expression of M2 and M3 receptors has shown that the proportion of M2 receptors often predominates over the M3 receptor population by 4:1 or more. Although it is established that M2 receptors preferentially link, via a pertussis-toxin-sensitive G protein Gi, to inhibition of adenylate cyclase activity, relatively little is known concerning the physiological role of the M2 receptor population. In this review, Richard Eglen and colleagues discuss recent data concerning the possible role(s) of muscarinic receptor subtypes in smooth muscle and appraise the pharmacological methods for dissecting the function of muscarinic receptor subtypes in tissues co-expressing multiple receptors.

Book ChapterDOI
01 Jan 1994
TL;DR: This chapter discusses the operation of the photoreceptors in plants growing in the natural environment and investigates their role in the selective advantage of signal-transducing photoreceptor properties.
Abstract: Why do plants have photoreceptors? What selective advantage does the possession of signal-transducing photoreceptors confer? Does the operation of the photoreceptors in plants growing in the natural environment reflect what we have learnt about them from laboratory experiments?

Journal ArticleDOI
TL;DR: The effects of prior experience and gender stereotyping upon the computer anxiety, confidence and liking of 144 male and female students who had just commenced their studies at university were examined in this paper.
Abstract: The effects of prior experience and gender stereotyping upon the computer anxiety, confidence and liking of 144 male and female students who had just commenced their studies at university were exam...

Journal ArticleDOI
TL;DR: The significant, albeit in some cases partial, protection provided against all nine pneumococcal serotypes supports the conclusion that pneumolysin toxoids warrant consideration for inclusion in a human vaccine.
Abstract: Pneumolysin is the thiol-activated cytolysin produced by Streptococcus pneumoniae. Mice were immunized with a genetically engineered toxoid version of pneumolysin, which was derived from a serotype 2 pneumococcus. The toxoid carried the mutation Trp-433-->Phe. Alum was used as the adjuvant. Immunized mice had significantly increased levels of anti-pneumolysin antibodies, principally immunoglobulin G1. Mice were challenged intraperitoneally or intranasally with 12 strains covering capsular serotypes 1 to 6, 7F, 8, and 18C. Following challenge, the survival rate and/or the time of death of nonsurvivors (survival time) was significantly greater than that of sham-immunized mice for all nine serotypes. However, differences in the degree of protection were noted between different strains. The route of challenge also appeared to influence the degree of protection. Nevertheless, the significant, albeit in some cases partial, protection provided against all nine pneumococcal serotypes supports the conclusion that pneumolysin toxoids warrant consideration for inclusion in a human vaccine.

Journal Article
TL;DR: It is proposed that the formation of large fragments of DNA represents a key committed step in apoptosis, and that it is from these fragments that the archetypal DNA ladders associated with apoptosis are derived.
Abstract: Apoptosis is a process in which cells die in a controlled manner and apparently participate in their own demise. It is best characterized morphologically by condensation of chromatin and biochemically by cleavage of chromatin at internucleosomal regions to yield a classical DNA ladder pattern. Apoptosis was induced in thymocytes by exposure to either the glucocorticoid, dexamethasone, or DNA topoisomerase II inhibitor, etoposide. We describe the formation of large m.w. fragments of DNA, 30 to 50 kilobase pairs in length, in a population of these thymocytes at an early stage of apoptosis before internucleosomal cleavage of DNA. These fragments are absent in normal thymocytes and their formation is dependent on protein synthesis. Their appearance is coincident with the commitment of these cells to apoptosis. The formation of these large fragments is associated with the condensation of chromatin, abutting the nuclear membrane, recognized as one of the earliest ultrastructural signs of apoptosis. Subsequent cleavage of these large fragments gives rise to oligonucleosomal fragments and is independent of protein synthesis. We propose that the formation of large fragments of DNA represents a key committed step in apoptosis, and that it is from these fragments that the archetypal DNA ladders associated with apoptosis are derived.

Journal ArticleDOI
TL;DR: In this paper, the involvement of phytochrome B in the early-flowering response of Arabidopsis thaliana L. seedlings to low red:far-red (R/FR) ratio light conditions was investigated.
Abstract: We have investigated the involvement of phytochrome B in the early-flowering response of Arabidopsis thaliana L. seedlings to low red:far-red (R/FR) ratio light conditions. The phytochrome B-deficient hy3 (phyB) mutant is early flowering, and in this regard it resembles the shade-avoidance phenotype of its isogenic wild type. Seedlings carrying the hy2 mutation, resulting in a deficiency of phytochrome chromophore and hence of active phytochromes, also flower earlier than wild-type plants. Whereas hy3 or hy2 seedlings show only a slight acceleration of flowering in response to low R/FR ratio, seedlings that are doubly homozygous for both mutations flower earlier than seedlings carrying either phytochrome-related mutation alone. This additive effect clearly indicates the involvement of one or more phytochrome species in addition to phytochrome B in the flowering response as well as indicating the presence of some functional phytochrome B in hy2 seedlings. Seedlings that are homozygous for the hy3 mutation and one of the fca, fwa, or co late-flowering mutations display a pronounced early-flowering response to low R/FR ratio. A similar response to low R/FR ratio is displayed by seedlings doubly homozygous for the hy2 mutation and any one of the late-flowering mutations. Thus, placing the hy3 or hy2 mutations into a late-flowering background has the effect of uncovering a flowering response to low R/FR ratio. Seedlings that are triply homozygous for the hy3, hy2 mutations and a late-flowering mutation flower earlier than the double mutants and do not respond to low R/FR ratio. Thus, the observed flowering responses to low R/FR ratio in phytochrome B-deficient mutants can be attributed to the action of at least one other phytochrome species.

Journal ArticleDOI
TL;DR: The structural characteristics of the rupture site of term fetal membranes (amniochorion and decidua) that rupture spontaneously after the onset of labour are studied.

Journal ArticleDOI
TL;DR: Pneumolysin-exposed cells produced significantly larger amounts of tumor necrosis factor alpha and interleukin-1 beta than cells not exposed to the toxin.
Abstract: Human peripheral blood monocytes and a human monocyte cell line were exposed to the toxin pneumolysin. Pneumolysin-exposed cells produced significantly larger amounts of tumor necrosis factor alpha and interleukin-1 beta than cells not exposed to the toxin. The viability of cells was not affected by the concentrations of pneumolysin used in the experiments.

Journal ArticleDOI
TL;DR: The precambrian of Madagascar is divided into two sectors by the north-west trending sinistral Ranotsara shear zone, which continues in the Mozambique belt and in Southern India as the Achankovil shear zones as discussed by the authors.
Abstract: The Precambrian of Madagascar is divided into two sectors by the north-west trending sinistral Ranotsara shear zone, which continues in the Mozambique belt, probably as the Surma shear zone, and in Southern India as the Achankovil shear zone. South of Ranotsara six north-south trending tectonic belts are recognized that consist largely of granulite and high amphibolite facies paragneisses, phlogopite diopsidites, concordant granites and granulites. North of Ranotsara the central-northern segment is traversed by a north-trending axial 100–150 km wide dextral shear zone of probable Pan-African age, which was metamorphosed under granulite and high amphibolite facies conditions and which has reworked older basement. This shear zone continues across southern India as the Palghat-Cauvery shear zone. Major stratiform basic -ultrabasic complexes occur in the axial zone and in the basement to the west. Well preserved low grade continental margin-type sediments (quartzites, mica schists and stromatolitic marbles) of Kibaran age are present in western Madagascar. Two partly greenschist grade sedimentary groups lie unconformably on high grade basement in north-east Madagascar. Isotopic age data suggest the presence in Madagascar of Archaean, Early and Mid-Proterozoic crustal material that was extensively reworked in Pan-African times.

Journal ArticleDOI
TL;DR: The effects on channel function of changing an aspartate residue (Asp172) in a membrane‐spanning alpha‐helix of the murine inward rectifier, IRK1, by site‐directed mutagenesis are described and the consequences for channel structure are discussed.
Abstract: 1. We describe the effects on channel function of changing an aspartate residue (Asp172) in a membrane-spanning alpha-helix of the murine inward rectifier, IRK1, by site-directed mutagenesis. 2. Alteration of Asp172 to Glu (charged) or to Gln or Asn (polar but uncharged) produced functional channels showing inward rectification, though rectification was weaker with Gln and Asn. 3. Intrinsic gating around the potassium equilibrium potential, EK, was conserved only if the charge on residue 172 was conserved. Currents through channels with Gln or Asn in this position showed no time dependence under hyperpolarization. 4. The change from Asp to Gln also reduced the affinity for internal Mg2+ at least fivefold, indicating that Asp172 also forms part of the site for Mg2+ blockage. 5. The consequences for channel structure of Asp172 lining the pore are discussed.

Journal ArticleDOI
01 Jun 1994-Diabetes
TL;DR: It is concluded that maternally inherited diabetes and deafness is a distinct subtype of diabetes that is associated with a single mitochondrial tRNALeu(UUR) mutation.
Abstract: We have recently reported an A to G transition at nucleotide position 3243 in the mitochondrial DNA (mtDNA) tRNA(Leu(UUR)) gene in a large family with non-insulin-dependent diabetes mellitus (NIDDM). Characteristic was its maternal transmission and an associated sensorineural hearing loss. In a screening of a Dutch and French NIDDM population for the presence of the tRNA(Leu(UUR)) mutation we identified two new pedigrees in which NIDDM is present in combination with deafness. The mode of inheritance agrees with a maternal one. This result shows that patients with a phenotype of NIDDM and deafness can be identified within groups of NIDDM patients based on the tRNA(Leu(UUR)) mutation. The same mutation has also been linked to the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). How the same mutation can give rise to different clinical phenotypes is not clear. We obtained the complete mtDNA sequence from our initial pedigree and identified a number of additional mutations that could confer the phenotype of the tRNA(Leu(UUR)) mutation to diabetes. We examined the presence of these additional, potentially pathogenic mutations in the mtDNA from the two new pedigrees and from a previously described British pedigree. The absence of these mutations in all three pedigrees shows that the tRNA(Leu(UUR)) mutation alone associates with the phenotype of NIDDM and deafness. We conclude that maternally inherited diabetes and deafness is a distinct subtype of diabetes that is associated with a single mitochondrial tRNA(Leu(UUR)) mutation. We propose the abbreviation MIDD for this particular subtype.

Journal ArticleDOI
TL;DR: The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction, finding early benefits of this simple and safe intervention are reflected in improved long-term survival.

Journal ArticleDOI
01 Mar 1994
TL;DR: In this paper, tetraethylammonium (TEA) was used to block the Drosophila maxi-K channel (Slowpoke) in Xenopus oocytes.
Abstract: Unitary currents were recorded from insideout membrane patches pulled from Xenopus oocytes that had been injected with RNA transcribed from a cDNA encoding the Drosophila maxi-K channel (Slowpoke). Site-directed mutagenesis was used to make cDNAs encoding channel subunits with single amino acid substitutions (Y308V and C309P). The extracellular side of the patch was exposed to tetraethylammonium (TEA) in the pipette solution; unitary currents in the presence of TEA were compared with currents in the absence of TEA to compute the inhibition. Amplitude distributions were fit by β functions to estimate the blocking and unblocking rate constants. For wild-type channels, TEA blocked with an apparent K d of 80 μM at 0 mV and sensed 0.18 of the membrane electric field; the voltage dependence lay entirely in the blocking rate constant. TEA blocked currents through C309P channels with a similar affinity to wild-type at 0 mV, but this was not voltage-dependent. Currents through Y308V channels were very insensitive to any block by TEA; the apparent K d at 0 mV was 26 mM and the blockade sensed 0.18 of the electric field. Oocytes injected with a mixture of RNAs encoding wild-type and Y308V channels showed unitary currents of four discrete amplitudes in the presence of 3 mM TEA; at 40 mV these corresponded to inhibitions of approximately 80%, 55%, 25% and 10%. These values agreed well with those expected for inhibition by TEA of currents through channels containing 3, 2, 1 and 0 tyrosine residues at the channel mouth, assuming that a tyrosine residue from each of four subunits contributes equally to the binding of the TEA ion. This indicates that Slowpoke channels form as tetramers.

Journal ArticleDOI
TL;DR: This article examined the characteristics and professional practices of specialist journalists involved in the coverage of science, medicine and related subjects in the British national press and found that they share many of their characteristics with specialist journalists in other areas: they value journalistic professionalism and skill more highly than formal training in their particular field of specialist reporting; they deploy conventional news-value criteria, but emphasize in particular the importance of a ''relevance to the reader' criterion in the selection of science news; and deploy elaborate routines for securing the credibility of their reporting.
Abstract: Newspaper coverage of science is governed and shaped by both macro-level factors such as ownership and cultural resonances, and by the more micro-level factors of journalistic practices, professional values, and organizational arrangements. This study examines the characteristics and professional practices of specialist journalists involved in the coverage of science, medicine and related subjects in the British national press. It shows that they share many of their characteristics with specialist journalists in other areas: they value journalistic professionalism and skill more highly than formal training in their particular field of specialist reporting; they deploy conventional news-value criteria, but emphasize in particular the importance of a `relevance to the reader' criterion in the selection of science news; they deploy elaborate routines for securing the credibility of their reporting, including the active cultivation of a relationship of mutual trust with their sources, and a source-orientation...

Journal ArticleDOI
TL;DR: The results suggest that both pp125FAK and paxillin undergo changes in tyrosine phosphorylation upon activation of rhoA, and that these changes are associated with the assembly of focal adhesions and actin stress fibres.
Abstract: Mouse Swiss 3T3 fibroblasts cultured in serum-free medium lose their actin stress fibres and vinculin-containing focal adhesions, a process that can be reversed by the addition of serum, lysophosphatidic acid (LPA) or bombesin, and is mediated by rhoA (A. J. Ridley and A. Hall (1992) Cell 70, 389-399). We have shown that the addition of serum to these cells induces the recruitment of the cytoskeletal proteins talin, vinculin and paxillin, and the protein kinases pp125FAK and PKC-delta, to newly formed focal adhesions, and that alpha-actinin is distributed along the actin stress fibres associated with these structures. The newly formed focal adhesions stained heavily with an antibody to phosphotyrosine. A similar response was elicited by 100 ng/ml LPA. The effect of serum was rapid, with focal staining for paxillin largely restricted to cell margins seen within 2 minutes of serum addition, and preceding the assembly of actin filaments. Phosphotyrosine staining differed in that it was predominantly punctate and was widely distributed throughout the cell. By 5 minutes, the paxillin and phosphotyrosine staining was concentrated at the ends of actin filaments largely at the cell margins. The structures stained ranged from circular to oval, but by 10 minutes they more closely resembled the elongated focal adhesions found in cultured fibroblasts. Within 10 minutes, the addition of serum or LPA induced a marked increase in the levels of pp125FAK and paxillin immune-precipitated by an anti-phosphotyrosine antibody. The results suggest that both pp125FAK and paxillin undergo changes in tyrosine phosphorylation upon activation of rhoA, and that these changes are associated with the assembly of focal adhesions and actin stress fibres. The observation that formation of focal adhesions can be induced by the tyrosine phosphatase inhibitor vanadyl hydroperoxide is consistent with the direct involvement of tyrosine phosphorylation in the assembly process. The localisation of PKC-delta to newly formed focal adhesions suggests that serine/threonine phosphorylation may also be important in this regard.

Journal ArticleDOI
01 Jan 1994-Eye
TL;DR: Comparison with the literature suggests that the results of treatment for amblyopia in this country may be falling far short of what would be possible in ideal circumstances with unlimited resources.
Abstract: SUMMARY The outcome of treatment for amblyopia and the factors that affect this are not well understood. A major reason for this has been the exclusion from previous large studies of a sometimes unknown number of patients because of failure to comply with treatment. This paper analyses the outcome of amblyopia treatment in a retrospective review of the orthoptic records of a cohort of 961 children treated for amblyopia at seven centres who first attended in 1983. The final visual acuity was recorded by Snellen or matching methods in 894 children (93 %). Of these, 48 % achieved 6/9 or better, 3S % less than 6/9 but better than or equal to 6/18, and 17 % achieved less than 6/18. The outcome was best for pure anisometropic amblyopia, intermediate for pure strabismic amblyopia and least good for mixed strabismic and anisometropic amblyopia with a final visual acuity of 6/10.2, 6/12.8 and 6/14.8 respectively . While the age at start of treatment did not correlate with final visual acuity both poor initial visual acuity and poor compliance were associated with poor outcome. The main factor affecting the outcome of amblyopia treatment is the initial visual acuity . Compari­ son with the literature suggests that the results of treat­ ment in this country may be falling far short of what would be possible in ideal circumstances with unlimited resources. There is a wide range in the reported results of treatments of amblyopia with success rates ranging from 30% to 92%.1,2 Reasons for this include the selection of patients and the exclusion from some studies of those not com­ pleting treatment. 3 There have been few studies with large numbers of patients which include information on chil­ dren who do not complete treatment and there have been no multicentre studies. This paper analyses factors associ­ ated with the outcome of amblyopia treatment in a multi­ centre study of 961 children treated for amblyopia and followed for up to 10 years.

Journal ArticleDOI
TL;DR: It is proposed that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF‐ϰB.