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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 487 records · Page 27Linked to original sources

Serologic response to the Borrelia burgdorferi flagellin demonstrates an epitope common to a neuroblastoma cell line.

Antibodies in sera of 7 patients with neurologic manifestations of Lyme borreliosis and a monoclonal antibody (mAb H9724) to the flagellin of Borrelia burgdorferi have been shown to bind neural tissue. To identify the antibody binding site common to the B. burgdorferi flagellin and the neural tissue, we made recombinant fusion proteins expressing epitopes of flagellin. Antibodies in patients' sera and mAb H9724 bound within an 18-amino acid epitope (residues 208-225) in the central region of flagellin, whereas two other mAbs bound to epitopes mapping elsewhere in the protein. Antibodies in patients sera and mAb H9724 also bound to a human neuroblastoma cell line. Absorption of patients sera with a peptide, EGVQQEGAQQPA, corresponding to amino acids 213-224 of flagellin, inhibited binding to the neuroblastoma cell line. The data suggest that the immune response to a specific B-cell epitope within flagellin, shared by a human neuroblastoma cell line, may be involved in the pathogenesis of neuroborreliosis.

Amino Acid Sequence↗

Hepatitis B immunization and exposure to blood among surgical staff.

A questionnaire was sent to all 158 staff of the operating department of a London teaching hospital to confirm their hepatitis B immunization status and establish the number of incidents involving exposure to blood during the preceding 4 weeks. Of these personnel, 104 (66 per cent) were known to be immune to hepatitis B either through immunization (97) or previous infection (seven). A further 23 (15 per cent) had completed a course of immunization but their seroconversion had not been checked. There were 26 sharps injuries sustained by 14 (12 per cent) of 119 staff and 240 other exposures to blood. Four of the sharps injuries had been reported. Staff known to be immune were more likely than those with unknown or negative immunity to report incidents (20 versus 0 per cent (95 per cent confidence interval of difference 2-38 per cent)). Doctors sustained more non-sharps exposures to blood than others (47 versus 23 per cent (95 per cent confidence interval of difference 7-40 per cent)). An important minority of operating department staff remains unimmunized against hepatitis B, although exposure to blood is common. Incidents are rarely reported and staff with unknown or negative immunity seem less likely to report than those known to be immune.

Blood↗

Hyperpolarizing synaptic potentials evoked in CA1 pyramidal cells by glutamate stimulation of interneurons from the oriens/alveus border of rat hippocampal slices. I. Electrophysiological response properties.

To examine the inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by interneurons situated at the stratum oriens/alveus border (O/A), glutamate was applied by micropressure to this area during intracellular recordings from CA1 pyramidal cells. Glutamate stimulation evoked IPSPs (glut-IPSPs) of small amplitude (4 mV), delayed peak latency (100-110 ms), and long duration (300-400 ms). Recurrent activation of interneurons via glutamate stimulation of pyramidal cells by local application in stratum pyramidale (PYR) evoked recurrent IPSPs (PYR glut-IPSPs) with similar amplitude and time course as O/A glut-IPSPs. The mean equilibrium potential of O/A glut-IPSPs (-77 mV) was significantly different from that of the PYR glut-IPSPs (-71 mV), however, neither equilibrium potential was significantly different from that of the electrically evoked early IPSP in the same cells. Glutamate-evoked IPSPs elicited from O/A displayed some response reversal (27% reversal) like those evoked from PYR (41% reversal). The early IPSP evoked by electrical stimulation displayed significantly more response reversal (67% reversal) than glut-IPSPs. Both types of glut-IPSPs (O/A and PYR) were associated with moderate increases in membrane conductance (5.9 and 6.6 nS, respectively), which were significantly less than the conductance change associated with the early IPSP (45.8 nS). In interneurons within PYR, glutamate stimulation in PYR readily elicited a flurry of excitatory postsynaptic potentials, whereas glutamate stimulation in O/A elicited IPSPs. The electrophysiological properties of IPSPs elicited in pyramidal cells by glutamate stimulation of interneurons in O/A were similar to those of recurrent IPSPs evoked from PYR. Given that both of these types of glutamate-evoked IPSPs were mostly mediated via GABAA receptor channels (Samulack DD, Lacaille J-C, 1993, Hippocampus 3:345-358), the small differences observed between equilibrium potentials, response reversals, and conductance changes could be due to a more electronically distant location from the soma of the synapses involved in O/A glut-IPSPs as compared to those of recurrent IPSPs elicited from PYR.

Animals↗

Can monoclonal antibody staining by 323/A3 and Ca1 of benign breast biopsies predict the development of breast cancer?

Monoclonal antibodies (mAb) raised to Ca1 and 323/A3 proteins have been suggested as markers of the premalignant breast. To establish the validity of this hypothesis the immunohistochemical staining patterns of these mAb have been studied in two different groups of patients with benign breast disease. One group comprised patients with benign biopsies who later went on to develop breast cancer. The second group were patients with benign breast disease who have not developed breast cancer. The immunohistochemical staining patterns of the two groups were compared. The staining patterns between the groups, when ducto-lobular, apocrine metaplasia and fibroadenomatous tissue were analysed, was similar. This occurred both for Ca1 and 323/A3 mAb. We conclude that the antigens identified by these mAb will not enable prediction of cancer development.

Adult↗

Meniscal nodule.

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Adult↗

Fed-batch culture of insect cells: a method to increase the yield of recombinant human nerve growth factor (rhNGF) in the baculovirus expression system.

A fed-batch method was developed which increased the density of insect cells (Spodoptera frugiperda, Sf-9 cells) in suspension culture and the feeding of nutrients improved the yield of a recombinant protein produced by a baculovirus expression system. Analysis of spent medium samples indicated that depletions of glucose and glutamine correlated with the retardation of cell growth. Feeding of a mixture of nutrients consisting of glucose, glutamine, yeastolate and lipids solution restored the growth rate. In fed-batch culture, cell density was increased from 3 x 10(6) cells per ml to 1.2 x 10(7) cells per ml and the increased cell density enhanced the yield of the desired recombinant product, in this case, human nerve growth factor (rhNGF). The optimal conditions for the production of rhNGF were also defined by selecting the appropriate viral multiplicity of infection (MOI). At a cell density of 5 x 10(6) ml-1, a MOI of 0.05 (plaque forming units per cell) gave the highest yield of rhNGF in culture fluid 3 d post-infection. The yield of rhNGF was 20 mg l-1. The fed-batch method was scaled up to 12 l stirred bioreactor.

Animals↗

Monosynaptic GABA-mediated inhibitory postsynaptic potentials in CA1 pyramidal cells of hyperexcitable hippocampal slices from kainic acid-treated rats.

To examine the mechanisms underlying chronic epileptiform activity, field potentials were first recorded to identify hyperexcitable hippocampal slices from kainic acid-treated rats. Intracellular recordings were then obtained from CA1 pyramidal cells in the hyperexcitable areas. Twenty-two of the 47 cells responded to electrical stimulation of the stratum radiatum with a burst of two or more action potentials and reduced early inhibitory postsynaptic potentials, and were considered hyperexcitable. The remaining 25 cells were not hyperexcitable, displaying a single action potential and biphasic inhibitory postsynaptic potentials after stimulation, like control cells (n = 20). A long duration, voltage-sensitive component was associated with subthreshold excitatory postsynaptic potentials in the majority of hyperexcitable (12/15) and non-hyperexcitable (3/5) cells examined from kainic acid-treated animals, but not from cells (1/10) of control animals. Stimulation of stratum radiatum during pharmacological blockade of ionotropic excitatory amino acid synaptic transmission elicited biphasic monosynaptic inhibitory postsynaptic potentials in all hyperexcitable (n = 9) and non-hyperexcitable (n = 9) cells tested from kainate-treated animals, as well as in control cells (n = 8). The mean amplitude, latency to peak, equilibrium potential, and conductance changes of early and late monosynaptic inhibitory postsynaptic potentials were not different between cells of kainic acid-treated and control animals. In seven hyperexcitable cells tested, the early component of monosynaptic inhibitory postsynaptic potentials was significantly reduced by the GABAA receptor antagonist bicuculline (100-200 microM). The late component was significantly decreased by the GABAB receptor antagonist 2-hydroxysaclofen (1-2 mM; n = 3). Comparable effects were observed on early and late monosynaptic inhibitory postsynaptic potentials in non-hyperexcitable cells (n = 4) from kainic acid-treated animals and control cells (n = 5). These results suggest that GABAergic synapses on hyperexcitable hippocampal pyramidal cells of kainate-treated rats are intact and functional. Therefore, epileptiform activity in the kainate-lesioned hippocampus may not arise from a disconnection of GABAergic synapses made by inhibitory interneurons on pyramidal cells. The hyperexcitability may be due to underactivation of inhibitory interneurons and/or reorganization of excitatory inputs to pyramidal cells since, in kainate-treated animals, pyramidal cells appear to express additional excitatory mechanisms.

2-Amino-5-phosphonovalerate↗

Type A behavior pattern and escalating commitment.

Subjects (N = 98) were randomly assigned to high- and low-responsibility conditions in a commitment-escalation experiment. Global Type A behavior pattern and the underlying dimension of achievement strivings were positively related to the desire to continue the same course of action in the high prior-responsibility condition but not in the low prior-responsibility condition. These findings are discussed in terms of future research into the judgment processes of people with Type A personality and the possible role of escalating commitment in disorders experienced by people with Type A personality.

Decision Making↗

Coronary heart disease prevention: the role of the general practitioner.

The objectives of the study were to identify the level of general practitioner (GP) involvement in activities aimed at coronary heart disease prevention and to explain variations in involvement. These questions were explored through a postal survey of a random sample (n = 1696) of GPs in England of whom 64% completed questionnaires. Ninety-four per cent of GPs reported that they were involved in risk factor assessment in the consultation although these assessments most commonly involved blood pressure testing and identification of smoking. Ninety-one per cent of practices were reported by the GP to have a lifestyle risk assessment clinic where there was more evidence of systematic risk assessment. These clinics were usually run by a practice nurse as were lifestyle risk factor management clinics although GPs were more involved in hypertension and cholesterol clinics. Positive attitudes to prevention and training in health promotion were associated with higher GP involvement, and higher practice involvement was associated primarily with the number of practice nurses employed. The implication of these findings are discussed.

Adult↗

Regulation of pathogenesis-related protein-1a gene expression in tobacco.

Pathogenesis-related protein-1a (PR-1a) is a protein of unknown function that is strongly induced during the onset of systemic acquired resistance (SAR) in tobacco. The expression of PR-1a is under complex regulation that is controlled at least partially by the rate of transcription. In this study, we demonstrated that 661 bp of 5' flanking DNA was sufficient to impart tobacco mosaic virus and salicylic acid inducibility to a reporter gene. The PR-1a promoter did not respond significantly to treatments with either auxin or cytokinin. Experiments with the protein synthesis inhibitor cycloheximide indicated that protein synthesis is required for salicylate-dependent mRNA accumulation. At flowering, the PR-1a gene was expressed primarily in the mesophyll and epidermal tissues of the leaf blade and the sepals of the flower. Several artifacts, most importantly ectopic expression in pollen, were associated with the use of the beta-glucuronidase reporter gene.

Adenine↗

Nursing staff requirements for neonatal intensive care.

A study to estimate the number of nursing staff required for neonatal nursing was undertaken. Certain nursing tasks, such as transporting any infant, caring for the dying infant, and looking after the very unstable infant required continuous attention by one nurse (5.5 whole time equivalent (wte) nurses for each cot). The stable ventilated infant required 10.5 nursing hours each day-that is, 2.4 wte/cot. Infants with intravenous infusions, but not ventilated, required only slightly less nursing time: 9.25 nursing hours each day or 2.12 wte/cot. Each special care patient needed 6.50 nursing hours each day, or 1.49 wte/cot. It is emphasised that each neonatal unit will have to take its own practices into account when calculating neonatal nursing requirements.

England↗

Strategies for teaching nursing research. Collaborative clinical research.

Formative evaluation of the CCRM model suggests that it is effective for students in fostering greater knowledge and skills in nursing research and an appreciation for the value of research in advanced nursing practice. The model has also generated enthusiasm in faculty and clinicians, as they work collaboratively with students to bridge the gap between theoretical and clinical aspects of nursing research.

Clinical Nursing Research↗

A comparison of five different methods for describing sagittal jaw relationship.

Analysis of sagittal jaw relationship is important in orthodontic diagnosis and treatment planning, and can be investigated by angular or linear parameters. In the present study an analysis was performed using profile cephalograms of 40 children with skeletal Class II malocclusion. A correlation analysis is presented, involving five different methods of expressing sagittal jaw relationships. Whilst some degree of agreement could be noted, it was not possible to suggest a pair of measurements, which in combination, could give a more accurate picture of sagittal jaw relationships.

Cephalometry↗

Islet amyloid polypeptide-like immunoreactivity in human tissue and endocrine tumors.

We have detected islet amyloid polypeptide (IAPP)-like immunoreactivity (-LI) in human pancreas and in a range of endocrine tumors, including oat cell carcinoma of the lung and pancreatic tumours producing insulin, gastrin, glucagon, and vasoactive intestinal peptide. Gel permeation chromatography of the IAPP-LI revealed that, except in the carcinoid, more than 80% coeluted with synthetic human IAPP. The remaining immunoreactivity consisted of variable amounts of larger and smaller molecular forms. The concentration of IAPP-LI in the circulation of patients with diagnosed pancreatic endocrine tumors was not significantly elevated above normal fasting levels. IAPP is, therefore, produced by a range of endocrine tumors and may relate to the deposition of endocrine amyloid.

Adult↗

The effectiveness of communication groups in day nurseries.

This project, run by a speech and language therapist and a clinical psychologist, took place in three inner city day nurseries. A group of children over whose communication there was concern were assessed on both formal (verbal and non-verbal) and informal (observational) measures. At each nursery these children were divided into two matched groups: intervention and control. The intervention consisted of communication groups run jointly with nursery staff. These small groups focused on promoting communication through play. On reassessment the children attending the communication groups had made significantly more improvement than the controls on both formal and informal measures. In particular, the number and quality of children's interactions, their underlying ability to focus on tasks and their knowledge of basic concepts appeared to benefit from the intervention. The study, therefore, provides strong evidence for the efficacy of such interventions in enhancing communication development in a real-life setting.

Child, Preschool↗

Expansion of neutrophil precursors and progenitors in suspension cultures of CD34+ cells enriched from human bone marrow.

The growth and differentiation of selected bone marrow CD34+ cells stimulated with hematopoietic growth factors in lipid cultures were evaluated to determine whether cell types that may be useful for reducing the neutropenia associated with high-dose chemotherapy (HDC) can be produced and quantitated in vitro. CD34+ cells enriched from bone marrow were cultured for up to 5 weeks in interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) with or without stem cell factor (SCF) (also termed c-kit ligand). The mixture of IL-3, GM-CSF and G-CSF resulted in an 18-fold increase in cells after 10 to 12 days of culture and a 94-fold increase after 21 days. A 3-fold increase in colony-forming unit granulocyte-macrophage (CFU-GM) was observed after 10 days of culture. The addition of SCF during the first 10 days of culture further augmented the proliferation of cell numbers to 24-fold and colony-forming cells (CFC) to 8-fold after 10 days while cell numbers increased 130-fold after 21 days. Two-color flow cytometry defined phenotypes expressing CD11b and CD15 that represented maturation stages of neutrophils. Maturation of neutrophils in these cultures could be followed by the initial appearance after 3 to 7 days of a CD15+CD11b- phenotype representing promyelocytes, which gave rise after 2 to 3 weeks to a CD15+CD11b+ phenotype representing more mature neutrophil forms (metamyelocytes to segmented neutrophils). In contrast to normal neutrophil development, only a small fraction (10 to 15%) of the culture-derived neutrophils expressed CD16. These data define the kinetics and differentiation of neutrophils and neutrophil precursors from selected CD34+ cells in liquid cultures.

Antigens, CD↗