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S Hill

Publications and source records attributed to S Hill.

At least 91 records · Page 5Linked to original sources
PubMed1998

Activated T-lymphocytes express occludin, a component of tight junctions.

T-lymphocytes routinely traffic from the lymphoid and vascular compartments to the tissues during immune surveillance and inflammatory responses. This egress occurs without compromising endothelial barrier, which is maintained by tight junctions (zonula occludens). We report that T-lymphocytes up-regulate the expression of occludin, a major component of the tight junction in response to stimulation with phorbol ester (PMA) + calcium ionophore, CD3 antibody or T-cell receptor (TCR) antibody. Only activated T-lymphocytes express occludin; this adhesion molecule is nearly absent in resting T-lymphocytes. By immunofluorescence, occludin is seen in lymphocyte aggregates, but does not appear to mediate aggregation since only 50% of the cells in these clusters express occludin. Occludin is expressed between 8 and 24 h following stimulation, and persists for at least 48 h. These data indicate that activated T cells produce occludin which may regulate lymphocyte adhesion and trafficking.

Animals↗
PubMed1998

The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains.

Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory flavoprotein that modulates the activity of the transcriptional activator NIFA in response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in vitro. Limited proteolysis of NIFL indicates that it comprises a relatively stable N-terminal domain and a C-terminal domain that is protected from trypsin digestion in the presence of adenosine nucleotides. ATP protects the protein from cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus, whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130 microM for ATP and 16 microM for ADP. The purified N-terminal domain has an identical UV/visible absorption spectrum to the wild-type protein and is reduced by sodium dithionite, demonstrating that it is a flavin-binding domain. The isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment containing 160 residues of the C-terminal region, including the nucleotide-binding sites, is also not competent to inhibit NIFA. Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response. However, this truncated protein remains competent to inhibit NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are therefore separable and are discrete functions of the protein.

Adenosine Diphosphate↗
PubMed1998

Epithelioid hemangioendothelioma presenting in the skin: a clinicopathologic study of eight cases.

Epithelioid hemangioendothelioma arising in the skin is extremely rare, and the majority of documented cases have developed in association with an underlying bone tumor. We report eight patients with an age range of 29-84 years (mean 53), who presented with primary cutaneous tumors at a variety of sites including the palm, shin, neck, knee, nose, back, and penis with a duration of between 6 and 12 months. Histologically, all eight cases presented as circumscribed nodules with an overlying acanthotic epidermis, three showing striking acrosyringeal proliferation, reminiscent of eccrine syringofibroadenoma. The tumors were composed of an admixture of slightly pleomorphic spindle and epithelioid cells with abundant, sharply defined eosinophilic cytoplasm and vesicular nuclei containing single nucleoli. Mitoses were generally sparse. All tumors showed intracytoplasmic lumina and intraluminal erythrocytes were occasionally apparent. The tumor cells were embedded in a myxoid or hyaline matrix. In contrast to visceral lesions, a vascular origin was not evident in any of our cases. The tumor cells variably expressed CD31, CD34, factor VIII-Rag, and smooth-muscle actin but not pankeratin or epithelial membrane antigen. Follow-up ranged from 4 months to 3 years. None of the lesions has thus far recurred and there have been no metastases.

Adult↗
PubMed1998

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗
PubMed1998

Overcoming cultural barriers to change.

This article is a case study which focuses on organisational and cultural change associated with the incorporation of a college which provided pre- and post-registration nursing and midwifery education into a much larger institution within the university sector. Among the issues addressed is whether transformational change, such as that represented by incorporation or merger, can be used by managers to successfully refashion the culture of the organisation, making more effective than traditional or discipline-based management structures. It examines the barriers to change and the various considerations that arose in determining the fit of managerial styles and assesses the outcomes of the process of change.

Education, Nursing↗
PubMed1998

Enzyme-linked immunosorbent assay for detection of feline herpesvirus 1 IgG in serum, aqueous humor, and cerebrospinal fluid.

Feline herpesvirus 1 (FHV) is an important cause of feline ocular and respiratory disease, but the role the virus plays in central nervous system disease of cats has not been explored. The study described here was performed to validate an indirect enzyme-linked immunosorbent assay (ELISA) to detect FHV-specific IgG antibodies for use in feline epidemiologic, ocular, and central nervous system disease studies. The indirect IgG ELISA was applied to serum, aqueous humor, and cerebrospinal fluid from cats. Serum FHV IgG ELISA results were compared with those of serum neutralization in client-owned cats and laboratory-housed cats following vaccination. Of the 100 client-owned cats tested by ELISA, 97 had detectable FHV IgG; 95 had titers >32. The FHV IgG ELISA was more sensitive than serum neutralization and could be used with aqueous humor and cerebrospinal fluid. Cats with inflammatory central nervous system or ocular diseases had significant leakage of serum proteins into aqueous humor and cerebrospinal fluid, necessitating use of cutoff values derived from serum when these fluids were assessed.

Animals↗
PubMed1998

Comparison of gel technology and red cell affinity column technology in antibody detection.

Both column (gel) agglutination technology and red cell affinity column technology (ReACT) have been approved by the Food and Drug Administration for antibody detection and identification. Parallel studies using these two methods were performed on 100 samples to evaluate their sensitivity, advantages, and disadvantages. Sixteen significant antibodies, anti-D(2), -C(1), -E(1), -c(1), -C,D(1), -K(4), -S(1), -Fya(3), -Jka(1), and -Jkb(1), were found during the study. MTS-Gel detected one anti-D due to Rh immune globulin but missed one anti-Jka. ReACT missed one anti-D and one anti-Jkb. MTS-Gel detected one anti-I and one anti-H whereas ReACT detected two anti- H but not anti-I. No false positive reactions were found by either method. Sensitivity based on this study for MTS-Gel is 93.3% and ReACT is 86.7%. Advantages for MTS-Gel included the small volume needed for testing, and the reaction was stable for 48 hours; for ReACT, there was less spin time and no special pipette was needed. Disadvantages for MTS-Gel included the need for a special pipette and manual preparation of 0.8% RBC suspensions, and the disadvantages for ReACT included the small column for reaction reading and the reaction was stable for only 24 hours.

Journal Article↗
PubMed1997

Measles control.

Explore the source record for details and available documents.

Humans↗
PubMed1997

Use of complementary therapies by individuals with 'arthritis'.

The popularity of complementary medicine is at an all-time high. Rheumatological patients are amongst its most frequent users. This survey was aimed at generating insight into this phenomenon. A self-selected convenience sample of 3384 individuals with 'arthritis' was sent a purpose-designed questionnaire. 1020 completed questionnaires were received (response rate = 30.1%). One third of respondents had received at least one treatment from a complementary practitioner. Orthodox therapies were generally perceived as more effective than complementary treatments. Therapeutic encounters with complementary practitioners were viewed as markedly more satisfying than those with GPs. Adverse effects reported in connection with orthodox treatments were more frequent and severe than those reported with complementary therapies. No firm conclusions can be drawn from these data. However, a hypothesis emerges that complementary medicine is well accepted by rheumatological patients and perceived to have certain advantages over mainstream medicine.

Adult↗
PubMed1997

How important are rhyme and analogy in beginning reading?

Current debate over the influence of phonological awareness on early reading development is polarised around small-unit (phoneme) processing and large-unit (onset-rime) processing. These opposing theories were contrasted by assessing the impact of pre-school phonological skills on reading amongst children experiencing their first year of formal instruction by a mixed method. Those beginning readers who could decode nonwords were found to have accomplished this by employing their letter-sound knowledge rather than by making analogies based on familiar rime units. Children displayed this pattern of performance regardless of their pre-school rhyming skills. Further investigations revealed that explicit awareness of onset and rime units was poor, even amongst children whose implicit rhyming skills were excellent. This evidence, together with the children's knowledge of orthographic units, was consistent with the view that letter-sound correspondences rather than onset or rime units formed the basis of their first attempts to utilise phonology in reading. The findings are discussed with reference to instructional influences on early reading and phonological awareness.

Child, Preschool↗
PubMed1997

Differential effects on TNF alpha production by pharmacological agents with varying molecular sites of action.

This study describes the activation conditions for tumor necrosis factor-alpha (TNF alpha) production in myelomonocytic U937 cells and human primary peripheral blood monocytes in response to lipopolysaccharide (LPS) and/or phorbol 12-myristate 13-acetate (PMA). PMA itself induced only low levels of TNF alpha production with delayed kinetics (e.g. 0.758 +/- 0.128 ng/ml from U937 cells after 48 h) while LPS induced greater levels of TNF alpha production in less time (e.g. 2.083 +/- 0.96 ng/ml from monocytes in 24 h). Pharmacological agents with various molecular sites of action were used to validate the two systems, with the protein serine-threonine kinase inhibitors staurosporine and Ro-31-8220, the protein tyrosine kinase inhibitor herbimycin A (HBA) and dexamethasone exhibiting the greatest potency (IC50S 5-350 nM). In contrast to the effect on TNF alpha production, PMA induced strong phosphorylation/activation of p42/p44mapk in monocytes by 10 min determined in a mobility shift assay, while LPS was a weaker inducer. Additionally, staurosporine (to LPS and PMA) and HBA (to LPS only) inhibited the activation of these mitogen-activated protein kinase (MAPK) isoforms at doses 10-100 fold higher than those required to inhibit maximal TNF alpha production. These data indicate the involvement of the p42/p44mapk signalling pathway in LPS-induced pro-inflammatory cytokine production but suggest that other signalling pathways are also implicated in this phenomenon.

Benzoquinones↗
PubMed1997

Effect of ketoconazole plus low-dose prednisone on progression of chronic renal failure.

Patients with any of four different types of chronic renal failure (CRF) (glomerular disease, interstitial nephritis, diabetic nephropathy, or polycystic disease) were observed using sequential determinations of glomerular filtration rate (GFR). Those whose GFR showed progression were either given ketoconazole 200 to 600 mg/d (to suppress cortisol production) plus prednisone 2.5 mg/d (to prevent anterior pituitary escape) and observed with the use of more GFRs, or were observed while four additional GFRs were determined before starting these drugs; some patients were subsequently withdrawn from these drugs and were observed using more GFRs. The effect of these drugs on rate of progression was estimated by a linear spline technique, using observations before, during, and (when available) after treatment. In 20 patients, sufficient data were obtained to estimate the magnitude of this effect. In seven patients with chronic glomerular disease, progressing at -0.62 +/- 0.12 mL/min/mo, progression slowed by 66% +/- 12% (P < 0.01). In five patients with interstitial nephritis of various etiologies, progressing at -1.19 +/- 0.34 mL/min/mo, progression slowed by 55% +/- 27% (P < 0.05). In five diabetic patients progressing at -1.22 +/- 0.14 mL/min/mo, progression slowed by an average of 77% +/- 14% (P < 0.01). In contrast, in four patients with polycystic kidney disease, progression accelerated by 99% +/- 63%. Mean urinary steroid excretion decreased significantly; plasma corticotropin did not increase. Neither proteinuria nor serum lipid levels changed. Urinary nitrate excretion decreased significantly, but serum nitrate did not change. Blood pressure decreased slightly (4.3 mm Hg). Three patients developed transiently elevated serum transaminase levels; two others withdrew because of side effects. We conclude that in chronic glomerular disease, diabetic nephropathy, and interstitial nephritis, this combination of drugs is as safe as ketoconazole in the absence of renal disease and shows promise of slowing progression. In polycystic kidney disease, it is apparently ineffective or harmful.

Adrenocorticotropic Hormone↗
PubMed1997

Respiratory protection of nitrogenase activity in Azotobacter vinelandii--roles of the terminal oxidases.

Nitrogen fixation by aerobic prokaryotes appears paradoxical: the nitrogen-fixing enzymes--nitrogenases--are notoriously oxygen-labile, yet many bacteria fix nitrogen aerobically. This review summarises the evidence that cytochrome bd, a terminal oxidase unrelated to the mitochondrial and many other bacterial oxidases, plays a crucial role in aerotolerant nitrogen fixation in Azotobacter vinelandii and other bacteria by rapidly consuming oxygen during uncoupled respiration. We review the pertinent properties of this oxidase, particularly its complement of redox centres, the catalytic cycle of oxygen reduction, the affinity of the oxidase for oxygen, and the regulation of cytochrome bd gene expression. The roles of other oxidases and other mechanisms for limiting damage to nitrogenase are assessed.

Azotobacter vinelandii↗