Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 109 records · Page 6Linked to original sources

PubMed2001

Design and assembly of solid-phases for the effective recovery of nanoparticulate bioproducts in fluidised bed contactors.

Practical recovery of nanoparticulate bioproducts from suspension feedstocks has been studied in batch, fixed bed and fluidised bed adsorptive contactors. The performance of five discrete configurations of adsorbent solid phase has been critically evaluated in the anion exchange recovery of mg quantities of BSA nanoparticles. These have served as surrogate size mimics of less easily sourced viral and plasmid gene therapy vectors, characterised by high value and a shortage of supply in quantities sufficient for research and development. Performance parameters of binding capacity, efficacy of washing, desorption efficiency and total cycle time were strongly influenced by the external and internal topographies of solid phases, together with the localised concentrations of interacting chemical ligands which modulate adsorption. In respect of a full operational recovery cycle, porous adsorbents developed for refined chromatographic fractionation of macromolecules, appear less suited overall than solid, nonporous particles, or solid particles coated with a shallow pellicle of active adsorbent material. Such findings have been confirmed in a detailed demonstration of the recovery of plasmid DNA (7.8 Kb) from chemical lysates of Escherichia coli.

Adsorption↗

PubMed2001

H9724, a monoclonal antibody to Borrelia burgdorferi's flagellin, binds to heat shock protein 60 (HSP60) within live neuroblastoma cells: a potential role for HSP60 in peptide hormone signaling and in an autoimmune pathogenesis of the neuropathy of Lyme disease.

Although Borrelia burgdorferi, the causative agent of Lyme disease, is found at the site of many disease manifestations, local infection may not explain all its features. B. burgdorferi's flagellin cross-reacts with a component of human peripheral nerve axon, previously identified as heat shock protein 60 (HSP60). The cross-reacting epitopes are bound by a monoclonal antibody to B. burgdorferi's flagellin, H9724. Addition of H9724 to neuroblastoma cell cultures blocks in vitro spontaneous and peptide growth-factor-stimulated neuritogenesis. Withdrawal of H9724 allows return to normal growth and differentiation. Using electron microscopy, immunoprecipitation and immunoblotting, and FACS analysis we sought to identify the site of binding of H9724, with the starting hypotheses that the binding was intracellular and not identical to the binding site of II-13, a monoclonal anti-HSP60 antibody. The current studies show that H9724 binds to an intracellular target in cultured cells with negligible, if any, surface binding. We previously showed that sera from patients with neurological manifestations of Lyme disease bound to human axons in a pattern identical to H9724's binding; these same sera also bind to an intracellular neuroblastoma cell target. II-13 binds to a different HSP60 epitope than H9724: II-13 does not modify cellular function in vitro. As predicted, II-13 bound to mitochondria, in a pattern of cellular binding very different from H9724, which bound in a scattered cytoplasmic, nonorganelle-related pattern. H9724's effect is the first evidence that HSP60 may play a role in peptide-hormone-receptor function and demonstrates the modulatory potential of a monoclonal antibody on living cells.

Antibodies, Monoclonal↗

PubMed2001

Anxiety and depression in mothers of children undergoing bone marrow transplant: symptom prevalence and use of the Beck depression and Beck anxiety inventories as screening instruments.

This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview. An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least I of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder.

Adolescent↗

PubMed2001

Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period.

This set of experiments investigated the appetitive or motivational processes underlying the performance of maternal behavior. The place preference paradigm was adapted to simultaneously investigate the reinforcing properties of cocaine and pups for maternal, lactating dams. These modifications allowed the authors to assess which stimulus, either a 10 mg/kg s.c. injection of cocaine or 3 pups, had the strongest reinforcing value. At Postpartum Days 10 and 16, the dams preferred the cocaine cue-associated chamber, whereas the dams tested at Postpartum Day 8 preferred the pup cue-associated chamber. Overall, the data revealed an interaction between the postpartum period at testing and the exhibited preference for cocaine or pups. Further testing will investigate the neural circuitry underlying the appetitive processes of each stimulus.

Animals↗

PubMed2001

Separation of cannabinoid receptor affinity and efficacy in delta-8-tetrahydrocannabinol side-chain analogues.

1. The activities of a number of side-chain analogues of delta-8-tetrahydrocannabinol (Delta(8)-THC) in rat cerebellar membrane preparations were tested. 2. The affinities of each compound for the CB(1) receptor were compared by their respective abilities to displace [(3)H]-SR141716A and their efficacies compared by stimulation of [(35)S]-GTPgammaS binding. 3. It was found that the affinities varied from 0.19+/-0.03 nM for 3-norpentyl-3-[6'-cyano,1',1'-dimethyl]hexyl-Delta(8)-THC to 395+/-66.3 nM for 5'-[N-(4-chlorophenyl)]-1',1'-dimethyl-carboxamido-Delta(8)-THC. 4. The efficacies of these compounds varied greatly, ranging from the very low efficacy exhibited to acetylenic compounds such as 1'-heptyn-Delta(8)-THC and 4'-octyn-Delta(8)-THC to higher efficacy compounds such as 5'-(4-cyanophenoxy)-1',1'-dimethyl-Delta(8)-THC and 5'-[N-(4-aminosulphonylphenyl)]-1',1' dimethyl-carboxamido Delta(8)-THC. All agonist activities were antagonized by the CB(1)-selective antagonist SR141716A. 5. It was found that a ligand's CB(1) affinity and efficacy are differentially altered by modifications in the side-chain. Decreasing the flexibility of the side-chain reduced efficacy but largely did not alter affinity. Additionally, the positioning of electrostatic moieties, such as cyano groups, within the side-chain also has contrasting effects on these two properties. 6. In summary, this report details the characterization of a number of novel Delta(8)-THC analogues in rat cerebellar membranes. It provides the first detailed pharmacological analysis of how the inclusion of electrostatic moieties in the side-chain and also how alteration of the side-chain's flexibility may differentially affect a CB(1) cannabinoid receptor ligand's affinity and efficacy.

Animals↗

PubMed2001

CD34(+) cell collection efficiency does not correlate with the pre-leukapheresis hematocrit.

One hundred and seventy-seven large-volume leukapheresis procedures performed on 91 patients over a 15 month period were reviewed to see if the pre-apheresis hematocrit (Hct) affected the CD34(+) cell collection efficiency (CE) of the Fenwal CS 3000 Plus cell separator. The Hct was 0.174-0.461 (median 0.317), and the peripheral blood CD34(+) cell count 2-2487 per microl (median 21). The total CD34(+) cell quantity collected was 3.0-2677.2 x 10(6) (median 113.0). Based on the number of CD34(+)cells contained in the blood volume processed (23.3-37303.2 x 10(6); median 318.0), the CE was 1.7-87.5% (median 30.3). No correlation was found between the Hct and CE (r(2) = 0.0034; P = 0.44) or the total CD34(+) cell quantity collected (r2 = 0.0040; P = 0.40). CEs for Hct <0.25 (median CE 36%), Hct 0.25-0.299 (median CE 30%) and Hct 0.30 (median CE 30%) were comparable. As expected, highly significant correlations were seen between the CD34(+) cell quantities collected and quantities processed (r2 = 0.59; P < 10(-6)) as well as the peripheral blood CD34(+) cell counts (r2= 0.60; P < 10(-6)). We conclude that the minimum acceptable Hct or hemoglobin level for leukapheresis should be dictated by clinical circumstances because it does not affect stem cell collection.

Antigens, CD34↗

PubMed2001

Overweight at age 21: the association with body mass index in childhood and adolescence and parents' body mass index. A cohort study of New Zealanders born in 1972-1973.

BACKGROUND: Obesity is an increasing problem so understanding the association between childhood and adolescent measures of body mass index (BMI) and being overweight at age 21 has implications for treatment or strategies to reduce its prevalence. OBJECTIVE: To examine the association between measures of BMI in childhood and adolescence and parents' BMI and being overweight at age 21. DESIGN: The study was based on a birth cohort born in Dunedin, New Zealand in 1972-1973. RESULTS: BMI tracked from childhood to early adulthood. The point on the BMI distribution where the probability of being overweight at age 21 was 0.5 was close to the 75th centile for boys throughout childhood and adolescence. It was rather higher for girls in childhood but similar in adolescence. Boys with a BMI above the 75th centile at age 7 were more than 4.0 times more likely to be overweight at age 21 than those with a BMI below the median. The relative risk for girls was 3.2. By age 15 this increased to 9.8 for males and 6.8 for females. Having overweight parents, particularly a mother, increased the likelihood of being overweight. Only 40% of those who were overweight at age 21 could be identified by age 7 and 25% were not identified until they were at least 15. CONCLUSION: Although a high BMI in childhood predicts being overweight at age 21, many of those who were overweight at age 21 had a BMI below the 75th centile or even the median in childhood and early adolescence. Population strategies, complemented by an individual approach for those above the 75th centile, are needed to reduce the average BMI of the population.

Adolescent↗

PubMed2001

Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome.

We describe a new mutation in glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome (BSS). Sequencing of GPIX revealed a homozygous (T-->C) transition at nucleotide 1717 (GenBank/HUMGPIX/M80478), resulting in a Cys(8) (TGT)-->Arg (CGT) replacement in the mature peptide. DNA restriction enzyme analysis using BsaAI revealed that the patient was homozygous and that his parents were heterozygous for the defect. This mutation disrupts a putative disulphide bond between the Cys(8) and Cys(12) that would alter the secondary structure of GPIX and which probably accounts for the absence of the GPIb/IX/V complex from the platelet surface in this patient.

Base Sequence↗

PubMed2001

Introducing an in-patient treatment for alcohol detoxification into a community setting.

Alcohol detoxification in the UK is not standardized and treatment is usually determined by local policies. Drug regimens are often predetermined and unrelated to the extent and duration of dependence, recent consumption, or previous withdrawal symptoms. Diazepam loading shortens the detoxification period and avoids the indiscriminate use of medication. It has been shown to be effective as an in-patient treatment. This paper examines the feasibility of introducing diazepam loading in a community setting, and discusses the implications that this would have for clinical practice.

Absenteeism↗

PubMed2001

Consumers' views of quality in the consultation and their relevance to 'shared decision-making' approaches.

BACKGROUND: There is a recognized need to assess the effects of shared decision-making and other communication interventions. However, the outcomes usually assessed for evidence of 'effectiveness' are determined by researchers and have not been based on consumers' views. AIM: This study aimed to identify the important outcomes of consultations for consumers, and to compare with those reported in the current literature. SETTING AND PARTICIPANTS: Forty-seven participants attending six focus group interviews. Most interviews took place in and all were orientated towards the UK primary care setting. METHODS: Focus group study. RESULTS: Many affective outcomes were identified, consistent with the current literature trends. However, many cognitive and behavioural outcomes that are assessed in the current literature were not noted by participants as important. Furthermore, a broader range of outcomes than is evident in the current literature was viewed as important to these participants. CONCLUSIONS: There is a need to revisit the outcomes which are assessed in decision-making and communication research. The outcomes of greatest importance to consumers must be identified and confirmed by new research which is based directly on the views of consumers themselves.

Consumer Behavior↗

PubMed2001

The chemokine interleukin-8 acutely reduces Ca(2+) currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs.

The chemokine IL-8 is known to be synthesized by glial cells in the brain. It has traditionally been shown to have an important role in neuroinflammation but recent evidence indicates that it may also be involved in rapid signaling in neurons. We investigated how IL-8 participates in rapid neuronal signaling by using a combination of whole-cell recording and single-cell RT-PCR on dissociated rat septal neurons. We show that IL-8 can acutely reduce Ca(2+) currents in septal neurons, an effect that was concentration-dependent, involved the closure of L- and N-type Ca(2+) channels, and the activation of G(ialpha1) and/or G(ialpha2) subtype(s) of G-proteins. Analysis of the mRNAs from the recorded neurons revealed that the latter were all cholinergic in nature. Moreover, we found that all cholinergic neurons that responded to IL-8, expressed mRNAs for either one or both IL-8 receptors CXCR1 and CXCR2. This is the first report of a chemokine that modulates ion channels in neurons via G-proteins, and the first demonstration that mRNAs for CXCR1 are expressed in the brain. Our results suggest that IL-8 release by glial cells in vivo may activate CXCR1 and CXCR2 receptors on cholinergic septal neurons and acutely modulate their excitability by closing calcium channels.

Acetylcholine↗

PubMed2001

Isolated scaphotrapeziotrapezoid osteoarthritis: prevalence, symptomatology and associated scapholunate ligament disruption in a population presenting to an accident and emergency department with acute wrist injuries.

AIM: To determine the prevalence of isolated scaphotrapeziotrapezoid osteoarthritis in a population presenting to an Accident and Emergency Department of Leicester Royal Infirmary with acute wrist injuries. Also to identify the presence of scapholunate ligament disruption in this patient group and quantify symptoms and loss of function in terms of the modified system of Green and O'Brien, a recognized clinical scoring system. MATERIALS AND METHODS: A total of 1711 radiographs of patients attending the Accident and Emergency Department were prospectively reviewed over a 5-month period. Those patients with isolated scaphotrapeziotrapezoid osteoarthritis were invited for clinical review. RESULTS: Sixteen patients were identified with isolated scaphotrapeziotrapezoid osteoarthritis. Two had a poor Green and O'Brien score and evidence of scapholunate ligament disruption (P < 0.05). CONCLUSION: Isolated scaphotrapeziotrapezoid osteoarthritis has a prevalence of 1% in a population presenting to an Accident and Emergency Department with acute wrist injuries over the age of 30 years. Isolated scaphotrapeziotrapezoid osteoarthritis may be asymptomatic even though the changes in the joint are severe. Scapholunate ligament disruption is associated with a poor Green and O'Brien score, but is not present in the majority of cases. Higginson, A. P.et al. (2001). Clinical Radiology56, 372-374.

Acute Disease↗

PubMed2001

Pan-Thames survey of occupational exposure to HIV and the use of post-exposure prophylaxis in 71 NHS trusts.

OBJECTIVES: To review the management of occupational exposure to definite or suspected HIV-infected blood, following the introduction of the 1997 UK Department of Health guidelines on the use of post-exposure prophylaxis. METHODS: Cross-sectional telephone survey of protocols in 71 NHS Trusts in the Pan-Thames region. Retrospective postal survey of the management of each definite or suspected HIV blood exposure between 1 July 1997 and 30 June 1999. RESULTS: Sixty-two (93%) Trusts had a written protocol, with many specialties involved in exposure management. Twenty-four Trusts reported 171 occupational exposures to definite or suspected HIV-infected blood. Of 97 definite HIV exposures, eight (8%) were discovered on post-incident HIV testing of the source patient; to which most source patients agreed when approached. Seventy-two (74%) exposed health care workers started prophylaxis and 49 (68%) completed the recommended 4-week course. Only half of those whose exposures occurred more than 6 months ago were known to have had a follow-up HIV test. CONCLUSIONS: Although most Trusts have implemented the Department of Health's guidance, collecting data on individual exposures proved difficult. We suggest that a designated department in each Trust co-ordinates and records HIV exposure management. Routine HIV testing is acceptable to most source patients and is appropriate in areas with a high prevalence of HIV seropositivity.

Blood-Borne Pathogens↗

PubMed2001

Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study.

OBJECTIVE: Coronary artery bypass grafting on the beating heart through median sternotomy is a relatively new treatment, which allows multiple revascularization without the use of cardiopulmonary bypass. A prospective randomized study was designed to investigate the effect of coronary bypass with or without cardiopulmonary bypass on postoperative blood loss and transfusion requirement. METHODS: Two hundred patients with coronary artery disease were prospectively randomized to (1) on-pump treatment with conventional cardiopulmonary bypass and cardioplegic arrest and (2) off-pump treatment on the beating heart. Postoperative blood loss identified as total chest tube drainage, transfusion requirement, and related costs together with hematologic indices and clotting profiles were analyzed. RESULTS: There was no difference between the groups with respect to preoperative and intraoperative patient variables. The mean ratio of postoperative blood loss and 95% confidence interval between groups was 1.64 and 1.39 to 1.94, respectively, suggesting on average a postoperative blood loss 1.6 times higher in the on-pump group compared with the off-pump group. Seventy-seven patients in the off-pump group required no blood transfusion compared with only 48 in the on-pump group (P <.01). Furthermore, less than 5% of patients in the on-pump group required fresh frozen plasma and platelet transfusion compared with 30% and 25%, respectively, in the on-pump group (both P <.05). Mean transfusion cost per patient was higher in the on-pump compared with that in the off-pump group ($184.8 +/- $35.2 vs $21.47 +/- $6.9, P <.01). CONCLUSIONS: Coronary artery bypass grafting on the beating heart is associated with a significant reduction in postoperative blood loss, transfusion requirement, and transfusion-related cost when compared with conventional revascularization with cardiopulmonary bypass and cardioplegic arrest.

Blood Transfusion↗

PubMed2001

The role of blood loss and diet in the aetiology of mild iron deficiency in premenopausal adult New Zealand women.

OBJECTIVE: To investigate the role of blood loss and diet in the aetiology of mild iron deficiency (MID) in premenopausal New Zealand women. Mild iron deficiency was defined as low, but not necessarily exhausted, iron stores (i.e. serum ferritin <20 microg/L) in the absence of anaemia (i.e. haemoglobin > or =120 g/L). DESIGN: Cross-sectional study of a volunteer sample of premenopausal adult women. Information on habitual dietary intakes (using a specially designed and validated computerised iron food frequency questionnaire), health and demographic status, sources of blood loss (including menstrual blood loss estimated using a validated menstrual recall method), contraceptive use, height and weight, haemoglobin, serum ferritin and C-reactive protein were collected. SETTING: Dunedin, New Zealand during 1996/1997. PARTICIPANTS: Three hundred and eighty-four women aged 18-40 years. RESULTS: The characteristics that were associated with an increased risk of MID were: low meat/fish/poultry intake, high menstrual blood loss, recent blood donation, nose bleeds, and low body mass index. The protective factors included shorter duration of menstrual bleeding, and multivitamin-mineral supplement use in the past year. CONCLUSIONS: There are a number of potentially modifiable factors that appear to influence risk of MID. Women with low menstrual blood loss may be able to decrease their risk of MID by increasing their meat/fish/poultry intake, while those with a higher menstrual blood loss may be able to decrease their risk by decreasing their menstrual blood loss, perhaps by changing their method of contraception. Women should be encouraged to maintain a healthy body weight, and those who choose to donate blood, or who experience nose bleeds, should have their iron stores monitored.

Adolescent↗

PubMed2001

Characteristics of the audiometric notch as a clinical sign of noise exposure.

This study investigated variability in audiometric notch recognition by asking three clinicians to identify notches in the audiograms of 634 noise-exposed employees. Agreement between the raters was assessed, and three notch characteristics, frequency, depth and shape (a wide or narrow notch), were investigated as recognition factors. The proportions of positive tests reported by each rater were 0.26, 0.49 and 0.68, respectively. The 'all rater' index of agreement was 0.45, and the range for pairwise comparisons was 0.14 to 0.52. With recognition factors, rater 1 was most strongly influenced by depth, rater 2 by shape and rater 3 by a possible combination of criteria. To reduce variability we suggest that narrow notches should be at least 15 dB in depth, and that broad notches should have a depth of 20 dB, with a recovery of at least 10 dB at the high end. Care should also be taken to elicit a sufficient history of noise exposure, and ensure that there are no other explanations for the notch.

Audiometry↗

PubMed2001

Influenza A antigen exposure selects dominant Vbeta17+ TCR in human CD8+ cytotoxic T cell responses.

During acute human viral infections, such as influenza A, specific cytotoxic T lymphocytes (CTL) are generated which aid virus clearance. We have observed that in HLA-A*0201+ subjects, CTL expressing Vbeta17+ TCR and recognizing a peptide from the influenza A matrix protein (M1(58-66)) dominate this response. In experimental models of infection such dominance can be due to inheritance of a restricted T cell repertoire or acquired consequent on expansion of CTL bearing an optimum TCR conformation against the MHC-peptide complex. To examine how influenza A infection might influence the development of TCR Vbeta17 expansion, we studied influenza A-specific CTL in a cross-sectional study of 82 HLA-A*0201+ individuals from birth (cord blood) to adulthood. Primary M1(58-66) -specific CTL were detected in cord blood, but their TCR were diverse and depletion of Vbeta17+ cells did not abrogate specific cytotoxicity. In contrast following natural influenza A infection, TCR Vbeta17+ CTL dominated to the extent that only one of nine adult CTL lines retained any functional activity after in vitro depletion of Vbeta17+ CTL. These results suggest that the dominance of Vbeta17+ TCR among adult M1(58-66)-specific CTL results from maturation and focussing of the response driven by exposure to influenza, and have implications for optimum immunization strategies.

Adolescent↗

PubMed2001

Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR.

We have shown that the dominance of CD8+ T cells expressing TCR Vbeta17 in the adult HLA-A*0201-restricted influenza A/M1(58-66)-specific response is acquired following first antigen exposure. Despite the acquired dominance of Vbeta17+ cells, subdominant M1(58-66)-specific clones expressing non-Vbeta17+ TCR persist in all individuals. To determine whether the affinity of the expressed TCR for the HLA-A*0201/M1(58-66) complex could influence functional properties, M1(58-66)-specific clones expressing subdominant (non-Vbeta17+) TCR were compared to cytotoxic T lymphocyte (CTL) clones expressing dominant (Vbeta17+) TCR. The Vbeta17+ CTL required up to 10,000-fold lower amounts of M1 peptide to mediate lysis compared to CTL clones expressing other Vbeta gene segments. All Vbeta17+ CTL clones tested bound HLA-A*0201/M1(58-66) tetramer, but two of three CTL clones expressing other TCR did not bind tetramer. The inability of non-Vbeta17+ CTL to bind tetramer did not correlate with phenotype, CD8 dependence or with cytokine production profiles. This suggests a limitation for the use of tetramers in examining subdominant T cell responses. Together these findings suggest that Vbeta17+ CTL which dominate the HLA-A*0201-restricted CTL response against influenza A are not functionally distinct from subdominant non-Vbeta17+ CTL. The dominance of Vbeta17+ CTL is likely to result from a competitive advantage due to superior CTL avidity for the HLA-A*0201/M1(58-66) complex.

Adult↗