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Biomedical subjects

R Crossley

Publications and source records attributed to R Crossley.

14 recordsLinked to original sources
PubMed2005

The reliability and validity of general psychotic rating scales with people with mild and moderate intellectual disabilities: an empirical investigation.

BACKGROUND: Whilst assessment tools have been developed to diagnose schizophrenia in people with mild intellectual disabilities (IDs), little attention has been paid to developing reliable and valid dimensional measures of psychotic experiences with this population. This study investigates the reliability and validity of two such measures developed for the general adult psychiatric population, the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scales (PSYRATS), with a population of adults with mild IDs. METHOD: Sixty-two adults with mild IDs were interviewed using the PANSS and PSYRATS, and independently interviewed using the Psychiatric Assessment Schedule--Adults with Developmental Disability (PAS-ADD) to obtain psychiatric diagnoses to the criteria of the International Classification of Diseases--Tenth Revision (ICD-10). On the basis of ICD-10 diagnosis, participants were divided into three groups: psychosis (n=11); other mental health problem (n=14); no mental health problem (n=37). PANSS and PSYRATS subscale scores were compared across these three groups and were correlated with PAS-ADD symptom scores across a number of PAS-ADD symptom domains. RESULTS: All PANSS and PSYRATS subscales showed adequate internal reliability, largely good test-retest reliability, and logical inter-correlations between subscales. The PANSS positive symptoms and the PSYRATS auditory hallucinations subscales differentiated between the psychosis group and the other groups; the PANSS general symptoms subscale differentiated between the psychosis and no mental health problem groups; and the PANSS negative symptoms and the PSYRATS delusions subscales did not differentiate between the three groups. CONCLUSIONS: The PANSS and PSYRATS are promising measures for use with people with mild IDs and psychotic experiences, although further investigation of items relating to negative symptoms and delusions is warranted.

Adolescent↗
PubMed2004

Permanent vegetative state: usefulness and limits of a prognostic definition.

Jennett and Plum's 1972 naming of post-coma unresponsiveness as "persistent vegetative state (PVS)" characterised the condition as essentially irrecoverable and insentient. The evidence for these propositions was always weak, and they have been largely disproved by more recent research. Nonetheless, the definition and the attitudes it embodies remain generally accepted, resting as they do on a firm foundation of medical attitudes to disability and a public eagerness to evade uncomfortable facts. The first step in altering our approach to people with this form of communication impairment must be to rectify our understanding of the terminology.

Humans↗
PubMed1997

Remediation of communication problems through facilitated communication training: a case study.

Facilitated communication training (FCT) is an educational technique intended to allow people who cannot speak or sign fluently to develop the hand skills necessary to use other non-speech communication strategies. It involves support to the arm, wrist or hand of the student, who is thus enabled to control his pointing, and has recently been the subject of considerable debate. Critics of the technique have cast doubt on the existence of any language problem remediable by touch. This study discusses the case of a person who had a language problem that did not appear to be connected with overt neuromotor impairment, was not accompanied by behavioural disturbance, and was remediable by touch alone. The case raises some interesting questions about the relation of physical prompts to language use.

Child↗
PubMed1995

Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines and related compounds.

Modification of some 8-benzylidene-5,6,7,8-tetrahydroquinolines, which have good antiulcer activity, led to three distinct classes of compounds with good in vivo antiinflammatory activity. Initial efforts led to a series of alkenes derived from 5,6,7,8-tetrahydroquinolines substituted at the 8-position. A second approach concentrated on replacing the CH linkage of these 8-benzylidene-substituted compounds with other spacer groups and increasing the size of the cycloalkyl ring from a six- to seven-membered ring, which provided 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine analogues. Finally, the substituent was switched from the cycloalkyl ring to the 2-position of the pyridine ring. Variation of the 2-substituent was also examined. Optimal antiinflammatory activity after oral administration was found in both the rat carrageenan paw edema and rat developing adjuvant arthritis models with 2-substituted 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridines, and of particular interest was 27 (WY-28342).

Animals↗
PubMed1992

The essential bacterial cell-division protein FtsZ is a GTPase.

Cytokinesis defines the last stage in the division cycle, in which cell constriction leads to the formation of daughter cells. The biochemical mechanisms responsible for this process are poorly understood. In bacteria, the ftsZ gene product, FtsZ, is required for cell division, playing a prominent role in cytokinesis. The cellular concentration of FtsZ regulates the frequency of division and genetic studies have indicated that it is the target of several endogenous division inhibitors. At the time of onset of septal invagination, the FtsZ protein is recruited from the cytoplasm to the division site, where it assembles into a ring that remains associated with the leading edge of the invaginating septum until septation is completed. Here we report that FtsZ specifically binds and hydrolyses GTP. The reaction can be dissociated into a GTP-dependent activation stage that is markedly affected by the concentration of FtsZ, and a hydrolysis stage in which GTP is hydrolysed to GDP. The results indicate that GTP binding and hydrolysis are important in enabling FtsZ to support bacterial cytokinesis, either by facilitating the assembly of the FtsZ ring and/or by catalysing an essential step in the cytokinetic process itself.

Amino Acid Sequence↗
PubMed1986

Immunocytochemical differentiation of microtubules in the cytoskeleton of Giardia lamblia using monoclonal antibodies to alpha-tubulin and polyclonal antibodies to associated low molecular weight proteins.

In interphase trophozoites of Giardia lamblia, separate populations of microtubules constitute the four parts of the mastigont apparatus: flagella, ventral disc, funis and median body. Antigenic differences between the tubules have been investigated by light and electron immunocytochemistry after labelling with two monoclonal antibodies to alpha-tubulin (YL 1/2 and YOL 1/34 clones), and with polyclonal antibodies to Giardia tubule-associated proteins. Both anti-tubulins stained all tubules after isolated structures were fixed in formaldehyde, but different patterns of reactivity were shown by unfixed tubules. YL 1/2 antibodies labelled flagellar axonemes and basal bodies, funis and median body tubules. Disc microtubules were mostly unlabelled, but the antibody bound strongly to the outer edge of the disc where the ends of tubules are embedded. YOL 1/34 antibodies stained disc tubules uniformly, and cross-reacted with the median body but not with tubules of axonemes, basal bodies or funis. Antibodies to giardins 14A and 14B (approximately 30 000 Mr filament-forming proteins) localized these proteins in the microribbons attached to disc microtubules. The median body was also labelled by anti-giardins, indicating an ontogenetic relationship between this organelle and the ventral disc. A second set of approximately 30 000 Mr proteins with no immunoreactivity to anti-giardin was found in flagella purified without removing flagellar membranes. These polypeptides were Triton-soluble and therefore probably originated from an extra-axonemal site. A rabbit antiserum to the labile flagellar proteins specifically stained the two ventral flagella, but not the other six flagella on this cell.

Animals↗
PubMed1985

Assembly of 2.5 nm filaments from giardin, a protein associated with cytoskeletal microtubules in Giardia.

The giardins are a family of approximately 30000 Mr structural proteins found in microribbons attached to microtubules in the disc cytoskeleton of Giardia. After examining the solubility of giardins in various agents, a method has been developed to extract these polypeptides and subsequently precipitate them selectively. The giardin chains are soluble in 10 mM-HEPES/EDTA buffer at high pH and low ionic strength, but become insoluble in 10 mM-MES/EDTA buffer at pH 6.7 when the ionic strength is raised above 50 mM salt. By dialysing giardin extracts in turn against dissociating and reassembly buffers, the purification is obtained of a subset of giardin chains identified by sodium dodecyl sulphate/polyacrylamide gel electrophoresis as the cytoskeleton bands 14a, 14b and 15. The structures forming under assembly conditions are all composed of fine filaments, 2-3 nm in diameter. Filaments after the first cycle of assembly are found in bundles, narrow ribbons of two or three filaments, and large ordered tactoids. Assembly after a second cycle of solubilization yields a more uniform population of long ribbons. Both the tactoids and the second cycle ribbons are transversely banded at the 15 nm interval characteristic of microribbons in the cytoskeleton. Filaments in the tactoids are precisely placed at a centre-to-centre separation of 2.5 nm. Other structural features of the tactoids are discussed in relation to the association behaviour and possible dimensions of the giardin molecular subunit.

Animals↗
PubMed1983

Characterization of proteins from the cytoskeleton of Giardia lamblia.

Proteins from the axonemes and disc cytoskeleton of Giardia lamblia have been examined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. In addition to tubulin and the 30 X 10(3) molecular weight disc protein, at least 18 minor components copurify with the two major proteins in Triton-insoluble structures. The most prominent minor bands have the apparent molecular weights of 110 X 10(3), 95 X 10(3) and 81 X 10(3). Protein of 30 X 10(3) molecular weight accounts for about 20% of organelle protein on gels. In continuous 25 mM-Tris-glycine buffer it migrates mostly as a close-spaced doublet of polypeptides, which are here given the name giardins. Giardia tubulin and giardin have been purified by gel filtration chromatography in the presence of sodium dodecyl sulphate. Well-separated fractions were obtained that could be further characterized. Both proteins are heterogeneous when examined by isoelectric focusing. Five tubulin chains were detected by PAGE Blue 83 dye-binding after focusing in a broad-range ampholyte gel. Giardin is slightly less acidic than tubulin. On gels it splits into four major and four minor chains with isoelectric points in the pI range from 5.8 to 6.2. The amino acid composition of the giardin fraction has been determined, and compared to Giardia tubulin and a rat brain tubulin standard. Giardins are rich in helix-forming residues, particularly leucine. They have a low content of proline and glycine; therefore they may have extensive alpha-helical regions and be rod-shaped. As integral proteins of disc microribbons, giardins in vivo associate closely with tubulin. The properties of giardins indicate that in a number of respects - molecular size, charge, stoichiometry - their structural interaction with tubulin assemblies will be different from other tubulin-accessory protein copolymers studied in vitro.

Amino Acids↗
PubMed1983

Selective extraction with Sarkosyl and repolymerization in vitro of cytoskeleton proteins from Giardia.

Sarkosyl has been used to dissociate structures in cytoskeletons isolated from Giardia lamblia. Results from sodium dodecyl sulphate/polyacrylamide gel electrophoresis and from electron microscopy of insoluble residues show that the solubilization of components is partly selective. At low concentrations of detergent (less than 0.3%), microribbons and microtubules of the disc cytoskeleton disappear, but doublet microtubules from axonemes resist extraction. Consequently, the microribbon protein giardin is extracted into solution more completely than tubulin. Soluble proteins in 0.1% Sarkosyl have been fractionated by gel filtration chromatography in Bio-Gel P300. Giardin elutes in two positions: as a low molecular weight subunit, and in early fractions corresponding to a larger particle size in which subunits might be forming oligomers. Supernatants prepared in 0.5% Sarkosyl were diluted with 0.1 M-KCl or 0.1 mM-MgCl2 to bring about reaggregation of the cytoskeleton proteins. Reassembled structures seen in negatively stained preparations were polymorphic. Some tubulin ribbons of 5 nM protofilaments were identifiable' also there were large fibres and some flat sheets of very thin filaments. Electron micrographs of sheets have been analysed by optical diffraction. The transforms show that the lateral separation of the fine filaments is about 2.5 nm. Axial periodicities from features spaced along filaments were weak. A 3.75 nm layer-line has been detected, corresponding to a similar periodicity found earlier in microribbons.

Animals↗
PubMed1980

Preliminary methodology for controlled cost-benefit study of drug impact: the effect of cimetidine on days of work lost in a short-term trial in duodenal ulcer.

The phase II/III U.S. clinical drug trials for cimetidine (Tagamet) in duodenal ulcer were examined for their potential application to cost-benefit analysis. Data on "time lost from work" were obtained from a special protocol added to these short-term, double-blind trials of cimetidine. Sixty-four outpatients from the clinical trials remained from an original pool of 217 after exclusion of those subjects who were either retired, unemployed, or of uncertain employment status. Cimetidine was significantly more effective than placebo in reducing "time lost from work" during ulcer disease. The patients' "time lost from work" occurred as a strikingly all-or-nothing phenomenon. We conclude that a prospective clinical trial is appropriate for gathering economic data.

Absenteeism↗
PubMed1977

5,6,7,8-Tetrahydroguinolines. 4. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinenitriles and -thioamides.

A number of 5,6,7,8-tetrahydroquinoling-8-nitriles and -8-thioamides and related compounds have been found to be potent inhibitors of basal gastric secretion in the pylorus-ligated rat and to afford protection against gastric erosions induced in rats by cold-restraint stress. Molecular manipulation has proved useful in determining factors necessary for such activity and structure-activity relationships are discussed. It has been shown that the most necessary requirements for activity are a pyridine nitrogen with its available lone pair and a primary or secondary thioamide. Also desirable is a six-membered carbocyclic ring with relative freedom from steric hinderance around the 8 position.

Animals↗
PubMed1977

5,6,7,8-Tetrahydroquinolines. 5. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinethioureas and related heterocycles.

A series of thioureas derived from 5,6,7,8-tetrahydroquinoline, 1,5-, 1,6-, and 1,8-naphthyridiness, pyrido[2,3-b]azepine, and 7-azaindoline has been prepared and tested for antisecretory activity in the pylorus-ligated rat and protective activity against gastric erosions caused by cold-restraint stress. The thioureas exhibit different structure-activity relationships from the corresponding 5,6,7,8-tetrahydroquinoline-8-thiocarboxamides and these relationships are discussed. The activity of the thioureas is less affected by structural differences than the corresponding thioamides although they probably have the same mode of action.

Animals↗