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K Shaw

Publications and source records attributed to K Shaw.

At least 19 recordsLinked to original sources
PubMed2001

Tyrosine hydrogen bonds make a large contribution to protein stability.

The aim of this study was to gain a better understanding of the contribution of hydrogen bonds by tyrosine -OH groups to protein stability. The amino acid sequences of RNases Sa and Sa3 are 69 % identical and each contains eight Tyr residues with seven at equivalent structural positions. We have measured the stability of the 16 tyrosine to phenylalanine mutants. For two equivalent mutants, the stability increases by 0.3 kcal/mol (RNase Sa Y30F) and 0.5 kcal/mol (RNase Sa3 Y33F) (1 kcal=4.184 kJ). For all of the other mutants, the stability decreases with the greatest decrease being 3.6 kcal/mol for RNase Sa Y52F. Seven of the 16 tyrosine residues form intramolecular hydrogen bonds and the average decrease in stability for these is 2.0(+/-1.0) kcal/mol. For the nine tyrosine residues that do not form intramolecular hydrogen bonds, the average decrease in stability is 0.4(+/-0.6) kcal/mol. Thus, most tyrosine -OH groups contribute favorably to protein stability even if they do not form intramolecular hydrogen bonds. Generally, the stability changes for equivalent positions in the two proteins are remarkably similar. Crystal structures were determined for two of the tyrosine to phenylalanine mutants of RNase Sa: Y80F (1.2 A), and Y86F (1.7 A). The structures are very similar to that of wild-type RNase Sa, and the hydrogen bonding partners of the tyrosine residues always form intermolecular hydrogen bonds to water in the mutants. These results provide further evidence that the hydrogen bonding and van der Waals interactions of polar groups in the tightly packed interior of folded proteins are more favorable than similar interactions with water in the unfolded protein, and that polar group burial makes a substantial contribution to protein stability.

Amino Acid Substitution↗
PubMed2001

Tryptophan and 5-hydroxytryptophan for depression.

BACKGROUND: 5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia. OBJECTIVES: To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Psychlit, and Embase) and specialized databases (Cochrane Controlled Clinical Trials Register, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trial Register); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. SELECTION CRITERIA: Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials. MAIN RESULTS: 108 trials were located using the specified search strategy. Of these, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. REVIEWER'S CONCLUSIONS: A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.

5-Hydroxytryptophan↗
PubMed2001

Effect of four laboratory decontamination procedures on the quantitative determination of cocaine and metabolites in hair by HPLC-MS.

The testing for drugs of abuse in hair is increasingly used to detect illicit substances. Laboratories have implemented various decontamination, or washing, procedures in order to eliminate concerns regarding potential contamination of the hair with drug from the environment. However, the effect of these decontamination procedures on drug incorporated into the hair shaft via systemic exposure is unknown. This study evaluated the effect of four simple laboratory wash procedures on the quantitative measurement of cocaine and its metabolites in hair from rats administered cocaine by intraperitoneal injection. Washes included (1) methanol only; (2) 0.1 M phosphate buffer, pH 6.0; (3) 0.1 M phosphate buffer, pH 8.0; and (4) isopropanol and phosphate buffer, pH 5.5. Cocaine and its major metabolites, benzoylecgonine, norcocaine, ecgonine methyl ester, and cocaethylene, were analyzed using high-performance liquid chromatography coupled to atmospheric pressure electrospray ionization mass spectrometry. All four washes resulted in significant differences from unwashed hair controls (p < or = 0.05) for some or all of the detectable analytes. Because different wash procedures lead to significant differences in the measured concentrations of analytes in hair known to contain drug, quantitative data must be interpreted cautiously based on the wash procedures employed.

Animals↗
PubMed2001

Effect of ethnicity on denial of authorization for emergency department care by managed care gatekeepers.

OBJECTIVE: After a pilot study suggested that African American patients enrolled in managed care organizations (MCOs) were more likely than whites to be denied authorization for emergency department (ED) care through gatekeeping, the authors sought to determine the association between ethnicity and denial of authorization in a second, larger study at another hospital. METHODS: A retrospective cohort design was used, with adjustment for triage score, age, gender, day and time of arrival at the ED, and type of MCO. RESULTS: African Americans were more likely to be denied authorization for ED visits by the gatekeepers representing their MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI = 1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be denied authorization for ED visits. The observational study design raises the possibility that incomplete control of confounding contributed to or accounted for the association between ethnicity and gatekeeping decisions. Nevertheless, the questions that these findings raise about equity of gatekeeping indicate a need for additional research in this area.

Adolescent↗
PubMed2001

cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging.

The parts of the RNA genome of infectious bronchitis virus (IBV) required for replication and packaging of the RNA were investigated using deletion mutagenesis of a defective RNA (D-RNA) CD-61 (6.1 kb) containing a chloramphenicol acetyltransferase reporter gene. A D-RNA with the first 544, but not as few as 338, nucleotides (nt) of the 5' terminus was replicated; the 5' untranslated region (UTR) comprises 528 nt. Region I of the 3' UTR, adjacent to the nucleocapsid protein gene, comprised 212 nt and could be removed without impairment of replication or packaging of D-RNAs. A D-RNA with the final 338 nt, including the 293 nt in the highly conserved region II of the 3' UTR, was replicated. Thus, the 5'-terminal 544 nt and 3'-terminal 338 nt contained the necessary signals for RNA replication. Phylogenetic analysis of 19 strains of IBV and 3 strains of turkey coronavirus predicted a conserved stem-loop structure at the 5' end of region II of the 3' UTR. Removal of the predicted stem-loop structure abolished replication of the D-RNAs. D-RNAs in which replicase gene 1b-derived sequences had been removed or replaced with all the downstream genes were replicated well but were rescued poorly, suggesting inefficient packaging. However, no specific part of the 1b gene was required for efficient packaging.

3' Untranslated Regions↗
PubMed2001

HIV adolescents show improved immune function following massage therapy.

HIV+adolescents (M CD4=466 mm3) recruited from a large urban university hospital's outpatient clinic were randomly assigned to receive massage therapy (n=12) or progressive muscle relaxation (n=12) two-times per week for 12 weeks. To assess treatment effects, participants were assessed for depression, anxiety and immune changes before and after treatment the 12 weeks treatment period. Adolescents who received massage therapy versus those who experienced relaxation therapy reported feeling less anxious and they were less depressed, and showed enhanced immune function by the end of the 12 week study. Immune changes included increased Natural Killer cell number (CD56) and CD56+CD3-. In addition, the HIV disease progression markers CD4/CD8 ratio and CD4 number showed an increase for the massage therapy group only.

Adolescent↗
PubMed2001

Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review.

BACKGROUND: Insulin-dependent diabetes mellitus, also known as type 1 diabetes, is a life-threatening condition and is the third most common chronic illness among young people. As a result of minimal or non-existent insulin production, people with diabetes must take over the normally automatic task of regulation of blood glucose levels. This is achieved by a complex regimen involving multiple, daily administrations of insulin coordinated with dietary intake and energy expenditure and monitored by blood glucose testing. OBJECTIVES: To examine the effectiveness of educational and psychosocial interventions for adolescents with type 1 diabetes designed to improve their diabetes management. Specifically, it addressed the following research questions: (1) Do educational and psychosocial interventions for adolescents with type 1 diabetes have beneficial effects on biological and psychosocial outcomes? (2) Are there types or features of interventions that have been shown to be more effective than others? (3) What evidence is there of the cost-effectiveness of interventions? METHODS: A search strategy was formulated, piloted and refined. Three journals were handsearched, 11 electronic databases were searched and personal contacts, flyers, conferences and websites were used to notify the research community of the review to access further literature. This process generated 10,535 abstracts, which, after screening, resulted in 367 articles identified for retrieval. This number was augmented by hand-searching, personal contact and exploding references, and a final total of 457 articles were scrutinised. Of these, 64 reports describing 62 studies were identified as empirical papers evaluating educational or psychosocial interventions. The relevant data were extracted from the papers and summary tables for each study were prepared. Where possible, effect sizes were computed for outcomes from studies that included a randomised control group (CG) and other relevant information. RESULTS: A descriptive analysis of the 62 studies was undertaken. Most studies (67.7%) were conducted in the USA and 41% were randomised controlled trials (RCTs), none of which were UK-based. Only 48% of the reports provided an explicit theoretical rationale for the intervention. The mean number of participants was 53.8. The studies took place in various settings, evaluated a variety of interventions, involved various interventionists, addressed various components and assessed the effects by a range of outcomes, including measures of metabolic control and psychological and behavioural outcomes. Follow-up assessments were relatively rare. RESULTS - THE EFFECTIVENESS OF INTERVENTIONS: The 25 RCTs were examined in more detail and three of the most effective were described in depth. Effect sizes could be calculated for 14 studies. The mean (pooled) effect size for psychosocial outcomes was 0.37 and 0.33 for glycated haemoglobin with outliers (0.08 without outliers), indicating that these interventions have small to medium beneficial effects on diabetes management outcomes. A narrative review of the 21 pre-post studies with no CG was performed, including evaluations of interventions conducted at summer camps, interventions for poorly controlled patients and educational interventions. All studies reported beneficial effects. RESULTS - COST-EFFECTIVENESS: Few studies addressed economic considerations associated with interventions, and the lack of information on costs and the diversity of outcomes included by investigators impeded cost- effectiveness comparisons. Shorter hospitalisation at diagnosis is at least as effective in achieving control and avoiding complications in adolescence as longer stays. Home care may result in improved outcomes but may not be cheaper than hospital care at diagnosis. Targeting poorly controlled subjects may reduce adverse events and hospitalisations and may be more cost-effective than generic interventions. There is a need for rigorous cost-effectiveness studies of educational and psychosocial interventions for adolescents with type 1 diabetes that include longer-term considerations. CONCLUSIONS: The following conclusions were drawn from this review: (1) Educational and psychosocial interventions have small to medium beneficial effects on various diabetes management outcomes. (2) Well-designed trials of such interventions are needed in the UK (no completed RCTs of educational or psychosocial interventions for adolescents with type 1 diabetes conducted in the UK were found). (3) The evidence, arising primarily from studies in the USA, provides a starting point for the design of interventions in the UK. (4) Quantitative and narrative analysis of the evidence suggested that interventions are more likely to be effective if they demonstrate the inter-relatedness of the various aspects of diabetes management. (ABSTRACT TRUNCATED)

Adolescent↗
PubMed2001

Managed care purchasing under SCHIP: a nationwide analysis of freestanding SCHIP contracts.

This Policy Brief is the third in a series that examines the State Children's Health Insurance Program (SCHIP), in particular, those state programs that operate directly under the authority of Title XXI of the Social Security Act rather than as an expansion of Medicaid (or a Medicaid demonstration initiative). This series is designed to examine how states structure and administer insurance programs for low-income children when they elect to administer separate SCHIP plans that exist outside of the requirements and constraints of Medicaid. Understanding how states use their flexibility under "separate SCHIP programs" (as they are termed) has become an increasingly important policy question, in the face of heightened interest on the part of Governors, the Bush Administration, and others in comprehensive Medicaid reform. The first two policy briefs in this series analyzed the entitlement status of separately administered SCHIP programs, as well as issues related to coverage design and the definition of medical necessity. This Policy Brief provides the first nationwide overview of how separate SCHIP programs structure "freestanding" SCHIP managed care contracts, i.e., contracts that exist independently of a state's Medicaid managed care agreements. Fifteen such "freestanding" contracts existed as of Calendar Year 2000, and we report here on their general terms of coverage, access, and care coordination. A forthcoming related study will examine behavioral health care in freestanding SCHIP agreements. Following a brief background and discussion of research methods, we present our principal findings and discuss their implications.

Child↗
PubMed2000

Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1.

The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. Through high capacity screening followed by chemical optimization, we identified a novel non-peptide CCR1 antagonist, R-N-[5-chloro-2-[2-[4-[(4-fluorophenyl)methyl]-2-methyl-1-piperazinyl ]-2-oxoethoxy]phenyl]urea hydrochloric acid salt (BX 471). Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3) with high affinity (K(i) ranged from 1 nm to 5.5 nm). BX 471 was a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX 471 demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. Pharmacokinetic studies demonstrated that BX 471 was orally active with a bioavailability of 60% in dogs. Furthermore, BX 471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. This study is the first to demonstrate that a non-peptide chemokine receptor antagonist is efficacious in an animal model of an autoimmune disease. In summary, we have identified a potent, selective, and orally available CCR1 antagonist that may be useful in the treatment of chronic inflammatory diseases.

Administration, Oral↗
PubMed2000

Leader switching occurs during the rescue of defective RNAs by heterologous strains of the coronavirus infectious bronchitis virus.

A defective RNA (D-RNA), CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was rescued (replicated and packaged) using four heterologous strains of IBV as helper virus. Sequence analysis of the genomic RNA from the four heterologous IBV strains (M41, H120, HV10 and D207) identified nucleotide differences of up to 17% within the leader sequence and up to 4.3% within the whole of the adjacent 5' untranslated region (UTR). Analysis of the 5' ends of the rescued D-RNAs showed that the Beaudette leader sequence, present on the initial CD-61, had been replaced with the corresponding leader sequence from the helper IBV strain but the adjacent 5' UTR sequence of the rescued D-RNAs corresponded to the original CD-61 Beaudette sequence. These results demonstrated that the phenomenon of leader switching previously identified for the coronaviruses murine hepatitis virus and bovine coronavirus (BCoV) also occurred during the replication of IBV D-RNAs. Three predicted stem-loop structures were identified within the 5' UTR of IBV. Stem-loop I showed a high degree of covariance amongst the IBV strains providing phylogenetic evidence that this structure exists and is potentially involved in replication, supporting previous observations that a BCoV stem-loop homologue was essential for replication of BCoV defective interfering RNAs.

5' Untranslated Regions↗
PubMed2000

Expression of reporter genes from the defective RNA CD-61 of the coronavirus infectious bronchitis virus.

The defective RNA (D-RNA) CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was used as an RNA vector for the expression of two reporter genes, luciferase and chloramphenicol acetyltransferase (CAT). D-RNAs expressing the CAT gene were demonstrated to be capable of producing CAT protein in a helper-dependent expression system to about 1.6 microgram per 10(6) cells. The reporter genes were expressed from two different sites within the CD-61 sequence and expression was not affected by interruption of the CD-61-specific ORF. Expression of the reporter genes was under the control of a transcription-associated sequence (TAS) derived from the Beaudette gene 5, normally used for the transcription of IBV subgenomic mRNA 5. The Beaudette gene 5 TAS is composed of two tandem repeats of the IBV canonical consensus sequence involved in the acquisition of a leader sequence during the discontinuous transcription of IBV subgenomic mRNAs. It is demonstrated that only one canonical sequence is required for expression of mRNA 5 or for the expression of an mRNA from a D-RNA and that either sequence can function as an acceptor site for acquisition of the leader sequence.

Animals↗
PubMed2000

Patient education. Behaviour management strategies in ADHD.

Attention deficit hyperactivity disorder or ADHD is a condition characterised by inattention, hyperactivity and impulsiveness. It is often managed by a combination of medication and behaviour modification techniques. This sheet outlines some useful strategies parents and teachers may undertake.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Are stimulants addictive in children? What the evidence says.

BACKGROUND: Prescription stimulants are widely used to treat attention deficit hyperactivity disorder in clinical practice. OBJECTIVE: A systematic review of the literature was performed to assess available evidence regarding the propensity for abuse and addiction liability of these medications. METHOD: Trials were searched in computerised general databases (Medline, Psychlit and Embase) and specialised (Cochrane Controlled Trials Register, Cochrane Collaboration); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. Studies had to have sufficient description of study methodology and statistical analysis to permit critical evaluation. Randomised controlled clinical trials, crossover studies, cohort studies and case control studies were included. Human studies only were considered for inclusion. RESULTS: Sixty-eight trials were located using the specified search strategy. Of these, fifteen trials met inclusion criteria: five randomised controlled trials; nine crossover studies and one cohort study. The propensity for abuse of prescription stimulants was demonstrated by analysis of drug self administration, discriminatory ability and comparison studies. Insufficient evidence was available regarding the addiction liability of stimulants. DISCUSSION: Prescription stimulants have the propensity for abuse. There is insufficient evidence available to assess their addictive potential.

Central Nervous System Stimulants↗
PubMed1999

Comparative studies of Nsc and Fmoc as N(alpha)-protecting groups for SPPS.

2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) is an alternative base-labile N(alpha)-protecting group to 9-fluorenylmethoxycarbonyl (Fmoc) for amino acids. The UV spectrum of the Nsc group exhibits moderate absorption at 380 nm which is excellent for real-time monitoring of the deprotection process. It also decreases the rearrangement of X-Asp, which can be a serious problem in SPPS.

Amino Acids↗