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Biomedical subjects

C Hadley

Publications and source records attributed to C Hadley.

13 recordsLinked to original sources
PubMed1999

A systematic comparison of protein structure classifications: SCOP, CATH and FSSP.

BACKGROUND: Several methods of structural classification have been developed to introduce some order to the large amount of data present in the Protein Data Bank. Such methods facilitate structural comparisons and provide a greater understanding of structure and function. The most widely used and comprehensive databases are SCOP, CATH and FSSP, which represent three unique methods of classifying protein structures: purely manual, a combination of manual and automated, and purely automated, respectively. In order to develop reliable template libraries and benchmarks for protein-fold recognition, a systematic comparison of these databases has been carried out to determine their overall agreement in classifying protein structures. RESULTS: Approximately two-thirds of the protein chains in each database are common to all three databases. Despite employing different methods, and basing their systems on different rules of protein structure and taxonomy, SCOP, CATH and FSSP agree on the majority of their classifications. Discrepancies and inconsistencies are accounted for by a small number of explanations. Other interesting features have been identified, and various differences between manual and automatic classification methods are presented. CONCLUSIONS: Using these databases requires an understanding of the rules upon which they are based; each method offers certain advantages depending on the biological requirements and knowledge of the user. The degree of discrepancy between the systems also has an impact on reliability of prediction methods that employ these schemes as benchmarks. To generate accurate fold templates for threading, we extract information from a consensus database, encompassing agreements between SCOP, CATH and FSSP.

Databases, Factual↗
PubMed1999

Successful recognition of protein folds using threading methods biased by sequence similarity and predicted secondary structure.

Analysis of our fold recognition results in the 3rd Critical Assessment in Structure Prediction (CASP3) experiment, using the programs THREADER 2 and GenTHREADER, shows an encouraging level of overall success. Of the 23 submitted predictions, 20 targets showed no clear sequence similarity to proteins of known 3D structure. These 20 targets can be divided into 22 domains, of which, 20 domains either entirely match a previously known fold, or partially match a substantial region of a known fold. Of these 20 domains, we correctly assigned the folds in 10 cases.

Algorithms↗
PubMed1998

The London-East Anglia randomized controlled trial of cognitive-behaviour therapy for psychosis. IV: Self-esteem and persecutory delusions.

OBJECTIVES: There has been a resurgence of interest in the view that persecutory delusions serve a function of defending self-esteem. An alternative account of levels of self-esteem in individuals with persecutory delusions is that they result from processes similar to those studied in people with depression (i.e. from the occurrence of a range of life experiences and how the individual interprets and copes with them). This study aimed to examine both hypotheses together for the first time, and, as the literature indicates that delusions may not share a common cause, attention was given to the possibility of the presence of subgroups. DESIGN: Data were examined cross-sectionally and longitudinally from a randomized controlled trial of cognitive behaviour therapy for 60 people with drug-resistant psychosis. METHOD: The study is based on the initial assessment of all participants on self-esteem, delusional conviction and a large number of demographic, clinical and cognitive measures. Longitudinal analyses were also carried out, and are reported separately for those who received the therapy intervention and those in the control group. RESULTS: Almost three-quarters of participants with persecutory delusions reported low self-esteem. Changes over time in total self-esteem correlated with changes in measures of mood and social functioning, but not conviction in persecutory delusions. The individuals who initially had normal levels of self-esteem displayed a different pattern of results from the majority of participants. CONCLUSION: Low self-esteem in people with drug-resistant persecutory delusions is common and, in most cases, can best be understood in terms of normal emotional processes. There was evidence that the majority of persecutory delusions do not fit either strong or weak formulations of the delusion-as-defence explanation and that there may be subgroups with differing aetiologies. These results need to be replicated, and extended to groups in which symptoms are not resistant to medication.

Adaptation, Psychological↗
PubMed1998

London-east Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: Follow-up and economic evaluation at 18 months.

BACKGROUND: A randomised controlled trial of cognitive-behavioural therapy (CBT) for people with medication-resistant psychosis showed improvements in overall symptomatology after nine months of treatment; good outcome was strongly predicted by a measure of cognitive flexibility concerning delusions. The present paper presents a follow-up evaluation 18 months after baseline. METHOD: Forty-seven (78% of original n = 60) participants were available for follow-up at 18 months, and were reassessed on all the original outcome measures (see Part I). An economic evaluation was also completed. RESULTS: Those in the CBT treatment group showed a significant and continuing improvement in Brief Psychiatric Rating Scale scores, whereas the control group did not change from baseline. Delusional distress and the frequency of hallucinations were also significantly reduced in the CBT group. The costs of CBT appear to have been offset by reductions in service utilisation and associated costs during follow-up. CONCLUSIONS: Improvement in overall symptoms was maintained in the CBT group 18 months after baseline and nine months after intensive therapy was completed. CBT may be a specific and cost-effective intervention in medication-resistant psychosis.

Adult↗
PubMed1997

London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase.

BACKGROUND: A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published. METHOD: Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used. RESULTS: Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide). CONCLUSIONS: CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome.

Adaptation, Psychological↗
PubMed1997

London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. II: Predictors of outcome.

BACKGROUND: Despite growing evidence of the effectiveness of cognitive-behavioural therapy (CBT) for psychosis, typically only about 50% of patients show a positive response to treatment. This paper reports the first comprehensive investigation of factors which predict treatment outcome. METHOD: In a randomised controlled trial of CBT for medication-resistant psychosis (see Part I) measures were taken at baseline of demographic, clinical and cognitive variables. Changes over time were assessed on the Brief Psychiatric Rating Scale and the relationship between potential predictor variables and outcome was investigated using analysis of variance and covariance. RESULTS: A number of baseline variables were identified as predictors of good outcome in the CBT group. Key predictors were a response indicating cognitive flexibility concerning delusions (P = 0.005) and the number of recent admissions (P = 0.002). Outcome was less predictable in the control group and was not predicted by any cognitive variable. CONCLUSIONS: Good outcome is strongly predicted in patients with persistent delusions by a cognitive measure, while this was not the case in controls. Thus we argue that positive outcome in CBT is due in part to specific effects on delusional thinking.

Adult↗
PubMed1996

Pediatric clozapine intoxication.

Clozapine is a tricyclic dibenzodiazepine derivative used as an antipsychotic in adults. Clozapine's safety in children has not been established. This report describes three unintentional clozapine ingestions in pediatric patients. These are the first reported cases of clozapine intoxication in children. All three patients demonstrated dramatic alterations in mental status and tone, and two demonstrated extrapyramidal effects. Serum clozapine levels obtained in two patients were within the average range of steady state plasma concentrations for adults. These cases show the dramatic presentations of pediatric ingestion of clozapine and the differences between adult and pediatric intoxications.

Antidepressive Agents, Tricyclic↗
PubMed1996

Bladder adenocarcinoma during pregnancy: a case report.

BACKGROUND: Renal tract neoplasms account for only 15% of all cases of hematuria and are rare before the age of 40. Few cases of bladder carcinoma diagnosed during pregnancy have been reported. CASE: Adenocarcinoma of the dome of the bladder caused hematuria beginning at 20 weeks' gestation but was not diagnosed until the postpartum period. CONCLUSION: Hematuria during pregnancy is usually associated with infection. However, neoplasms must be included in the differential diagnosis.

Adenocarcinoma, Mucinous↗
PubMed1985

Role of mevalonate in regulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured cells and their cytoplasts.

H4-II-E-C3 hepatoma cells in culture respond to lipid-depleted media and to mevinolin with increased sterol synthesis from [14C]acetate and rise of 3-hydroxy-3-methylglutaryl coenzyme A reductase levels. Mevalonate at 4 mM concentration represses sterol synthesis and the reductase, and completely abolishes the effects of mevinolin. Mevalonate has little or no effect on sterol synthesis or reductase in enucleated hepatoma cells (cytoplasts) or on reductase in cytoplasts of cultured Chinese hamster ovary (CHO) cells. The sterol-synthesizing system of hepatoma cell cytoplasts and the reductase in the cytoplasts of CHO cells were completely stable for at least 4 hr. While reductase levels and sterol synthesis from acetate followed parallel courses, the effects on sterol synthesis--both increases and decreases--exceeded those on reductase. In vitro translation of hepatoma cell poly(A)+RNAs under various culture conditions gave an immunoprecipitable polypeptide with a mass of 97,000 daltons. The poly(A)+RNA from cells exposed for 24 hr to lipid-depleted media plus mevinolin (1 microgram/ml) contained 2.8 to 3.6 times more reductase-specific mRNA than that of cells kept in full-growth medium, or cells exposed to lipid-depleted media plus mevinolin plus mevalonate. Northern blot hybridization of H4 cell poly(A)+RNAs with [32P]cDNA to the reductase of CHO cells gave two 32P-labeled bands of 4.6 and 4.2 K-bases of relative intensities 1.0, 0.61-1.1, 2.56, and 1.79 from cells kept, respectively, in full-growth medium, lipid-depleted medium plus mevinolin plus mevalonate, lipid-depleted medium plus mevinolin, and lipid-depleted medium. These values approximate the reductase levels of these cells. We conclude that mevalonate suppresses cholesterol biosynthesis in part by being a source of a product that decreases the level of reductase-specific mRNA.

Animals↗
PubMed1985

Inhibition of liver prenyltransferase by citronellyl and geranyl phosphonate and phosphonylphosphate.

Citronellyl- and geranylphosphonic acids and the corresponding phosphonylphosphates were made and tested as inhibitors of liver prenyltransferase. Kinetic analysis showed that citronellyl- and geranylphosphonylphosphate were powerful inhibitors of the enzyme, and that they were competitive inhibitors with geranyl diphosphate and noncompetitive inhibitors with isopentenyl diphosphate. Two inhibition constants, representing the equilibria [E][I]/[EI] = K5 and [ES1][I]/[ES1I] = K9, have been defined for the inhibitors. For citronellylphosphonylphosphate, the value of K5 was 1.25 microM and K9 was 3.30 microM; for geranylphosphonylphosphate, K5 = 1.50 microM and K9 = 1.60 microM. The phosphonates were very poor linear mixed noncompetitive inhibitors with respect to both substrates of the transferase.

Acyclic Monoterpenes↗
PubMedDate not supplied

Anti-Bak(a) neonatal alloimmune thrombocytopenia: possible prevention by intravenous immunoglobulin.

Neonatal alloimmune thrombocytopenia (NAIT) most commonly involves antibodies directed against the PlA1 antigen, but other platelet specific alloantigens have been associated with it. We describe the case of a mother whose first three infants developed NAIT secondary to anti-Bak(a) antibodies, while her fourth infant did not. The three affected infants were treated postnatally with platelet transfusions. The fourth infant was treated antenatally with one dose of intravenous immunoglobulin (IVIg) given to the mother. Postpartum analysis revealed the infant's platelets to be Bak(a)-positive but negative for elevated IgG. Maternal serum reacted with neonatal platelets in vitro, but cord serum was negative for antiplatelet antibodies. These clinical observations do not prove the efficacy of IVIg; however, they raise several questions: Why wasn't this infant thrombocytopenic? Why didn't the umbilical cord contain maternal antibody? Was the single dose of IVIg responsible for preventing NAIT? IVIg is currently under investigation in a clinical trial evaluating its effectiveness in preventing NAIT in mothers with anti-PlA1 antibodies, where it has shown some success. There have been no reports of the use against anti-Bak(a) antibodies. We suggest that a weekly dose schedule may not be necessary for all affected pregnancies, and antibodies with specificity other than anti-PlA1 may require less vigorous therapy.

Adult↗