Community pharmacists are increasingly supervising treatments.
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Community Pharmacy Services↗
Biomedical subjects
R Scott
Publications and source records attributed to R Scott.
Increased expression of IL-1beta converting enzyme in hippocampus after ischemia: selective localization in microglia.
Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the in vivo expression of one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neurons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity was not altered in these neurons. ICE-like immunoreactivity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of ischemic brains. These results provide the first evidence for the localization and induction of ICE expression in vivo after ischemia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.
Animals↗
Dynamics of human replication protein A subunit distribution and partitioning in the cell cycle.
Human replication protein A (RPA) is a three-sub-unit protein complex involved in DNA replication, repair, and recombination. To gain insight into the dynamics of subunit assembly, we examined the subcellular distribution of RPA subunits (p70, p34, and p11) during the cell cycle. All three subunits colocalized in G1 and S phases, showing a diffuse nuclear distribution in G1 but a dot-like nuclear pattern in S phase. During S phase, the subunits showed a pattern reminiscent of the replication granules/factories described by others as sites of replication machinery. In meta-phase, p70 preferentially associated with the spindle poles, p34 was found on chromosomes, and p11 remained in the cytoplasm. In telophase, p70 and p34 appeared in the forming daughter nuclei; p11 remained in the cytoplasm until G1. Among the three subunits only p34 was associated with the nuclear matrix and this association persisted throughout the cell cycle. We conclude that (i) RPA complex assembly is differentially regulated, (ii) the replication machinery may be anchored to the nuclear matrix, and (iii) RPA subunits partition during mitosis and sort into daughter nuclei by different routes.
Cell Cycle↗
Survival of patients with Turcot's syndrome and glioblastoma.
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Adenomatous Polyposis Coli↗
Different patterns of cytokine induction in cultures of respiratory syncytial (RS) virus-specific human TH cell lines following stimulation with RS virus and RS virus proteins.
Human peripheral blood mononuclear cell (PBMC) proliferative responses to live respiratory syncytial (RS) virus, formalin-inactivated RS (Fl-RS) virus, RS virus F (fusion) protein, and RS virus G (attachment) protein were assessed. All donors responded to challenge with whole RS virus antigens and F and G proteins. F protein responses elicited higher levels of response than equivalent concentrations of G protein in nine out of ten adult RS-seropositive donors. Stimulation of PBMC induced low levels of interleukin 2 (IL-2), interferon gamma (IFN-gamma), IL-4, and IL-10 production. Human RS virus-specific T cell lines were generated from peripheral blood cultures following in vitro stimulation with RS virus antigens. All lines generated were shown to be MHC class II restricted. Characterisation of the lines was carried out by determining the levels of IL-2, IFN-gamma, IL-4, and IL-10 in culture supernatants. T cell lines enriched for RS virus-specific cells provided a more sensitive system than PBMC cultures for the detection of cytokines. The pattern of cytokine production varied for the individual lines, and the detection of TH1 and TH2 cytokines was dependent on the nature of the stimulating RS virus antigen. Live RS virus induced a TH1 pattern of cytokines (IL-2 and IFN-gamma), whereas FI-RS virus induced the production of both TH1 and TH2 cytokines. In addition, TH lines specific for individual RS virus proteins produced different cytokine profiles. F protein-specific lines generated TH1-type cytokines (IL-2 and IFN-gamma), whereas G protein-specific lines generated TH2-type cytokines (IL-4 and IL-10).
Adult↗
Meeting the constraints upon behavioral expression through neural and genomic interactive mechanisms.
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Animals↗
Sensitivity of cell lines to mitomycin C.
OBJECTIVES: To determine the effect of pH on the cytotoxicity of mitomycin C on a wide range of established cell lines. MATERIALS AND METHODS: Cultures of three human tumour cell lines, including two bladder carcinomas and one renal adenocarcinoma, and two mouse cell lines were treated with mitomycin C (concentration range 320 pM-50 microM) at a range of pH (5.8-7.8) for 2 h. The cytotoxicity of mitomycin C over this range was determined using a tetrazolium-dye-based microtitration assay. RESULTS: The cytotoxicity of mitomycin C was significantly greater (confidence level > or = 95%) in acidic conditions (pH 5.8-6.0) than in neutral to alkaline pH (7.2-7.8) for three of the five cell lines. The same trend, although less marked, also occurred in the other two cell lines. CONCLUSION: The cytotoxicity of mitomycin C was greater under acidic conditions for all these cell lines confirming that the activity of mitomycin C depends on pH and suggesting that the pH of the vehicle used for intravesical chemotherapy may be an important factor in the successful treatment of bladder carcinomas. The modification of pH by urine may explain some of the variation in success rates among patients treated intravesically with mitomycin C.
Adenocarcinoma↗
Overexpression of p53 protein and its significance for recurrent progressive bladder tumours.
OBJECTIVE: To determine the prognostic value of the overexpression of p53 protein as determined by immunohistochemistry in recurrent progressive transitional cell carcinomas of the bladder. PATIENTS AND METHODS: A total of 222 tumours from 86 patients with recurrent disease, 20 from patients with no evidence of recurrence after resection of initial tumour and 11 normal bladder (controls) were investigated. Using a microwave technique to expose antigens, formalin-fixed sections were immunohistochemically stained for p53 using a polyclonal antiserum. Two independent observers scored the sections for evidence of overexpression of p53. RESULTS: Of 86 patients with recurrent disease, 51 demonstrated overexpression of p53 protein, as did six of 20 patients with non-recurrent disease. Overexpression was not linked to recurrence (P = 0.5) but was related to worsening histological stage (P < 0.01) and increasing grade (P < 0.01). Regression analysis showed that overexpression of p53 for the primary tumour was not of predictive prognostic value for death from bladder cancer, time to progression or time to recurrence. Tumour grade was the only variable of prognostic value in all the statistical models. Patients with overexpression of p53 showed no reduction in overall survival. CONCLUSION: These findings suggest that overexpression of p53, as determined immunohistochemically, appears to have no predictive prognostic value over stage and grade in bladder tumours.
Aged↗
Activity levels and cognitive functioning in an elderly community sample.
The influence of self-reported and informant-reported activity levels on Crystallized Intelligence, Fluid Intelligence, Memory and the Mini-Mental State Examination was investigated in a sample of 858 community-dwelling elderly subjects. Both self-reported and informant-reported activity levels explained variance beyond that accounted for by sex, sensory functioning, activities of daily living, medical conditions, current health problems and education. Age accounted for additional variance once activity and the other contextual variables were entered. Interaction effects indicated that inactivity was associated with poorer performance on fluid intelligence in older rather than younger elderly subjects and that inactivity was predictive of poor crystallized intelligence at younger ages. Higher informant-rated activity levels moderated the effects of education, so that higher activity offset effects associated with low education on memory tasks. The mount of variance explained by activity levels was modest.
Activities of Daily Living↗
Coeliac disease and familial hypercholesterolaemia.
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Aged↗
Recurrent abdominal pain and Helicobacter pylori in a community-based sample of London children.
Helicobacter pylori is accepted as an important factor in the pathogenesis of peptic ulcer disease. Infection is probably most commonly acquired in early life but there is still limited information on the prevalence or symptomatology of H. pylori infection in childhood. The aim of the present study was to establish the prevalence of H. pylori infection in a large sample of urban school children and to determine its relationship, if any, to a history of recurrent abdominal pain. Using a commercial ELISA significant levels of anti-H. pylori IgG antibody were detected in 107/640 (16.7%) of school children (M, 383; F, 257; mean age 9.15 years, range 4-13). No relationship was demonstrated between H. pylori seropositivity and a personal or family history of recurrent abdominal pain or the nature of the pain.
Abdominal Pain↗
Mental health and adequacy of social support: a four-wave panel study.
LISREL analyses with manifest variables were used to examine the causal relationship between mental health and adequacy of social integration and of attachment, measured at four consecutive waves each four months apart, in a representative sample of 225 adult residents in Canberra. Mental health was assessed with the 30-item General Health Questionnaire. The analyses suggest that while there is no temporal relationship between adequacy of attachment and mental health, adequacy of social integration is influenced by earlier mental health. The temporal relationship between adequacy of attachment and adequacy of social integration appears to be reciprocal.
Adult↗
Extracorporeal methods of vascular control for difficult IVC procedures.
Surgical procedures in the juxtaheptic and intrapericardial inferior vena cava (IVC) are difficult because of the complexity of achieving vascular control in the area. We describe 10 patients with a variety of pathologies in this region who underwent venovenous bypass (VVB) or cardiopulmonary bypass with hypothermic circulatory arrest (CBCA). Renal cell carcinoma with IVC extension was present in three patients (with tumor extension into the right atrium in two), adrenal adenocarcinoma in one, septic IVC thrombus in one, and blunt IVC/hepatic trauma in five. Those patients without atrial involvement underwent VVB with a mean bypass time of 40 minutes (range 12-144). Those patients with tumor extension into the right atrium underwent CBCA with systemic hypothermia to 18(0)C, total body exsanguination for a bloodless field, and removal of the tumor by cavotomy and right atriotomy. The mean bypass, aortic cross-clamp, and circulatory arrest times were 152, 92, and 36 minutes, respectively. Eight of the 10 patients did well and went home within 4 weeks of surgery. Two patients died, one from metabolic sequelae of exsanguinating IVC injury (VVB) and one from sepsis 2 weeks postoperatively (CBCA).
Adult↗
Modified venovenous bypass technique for resection of renal and adrenal carcinomas with involvement of the inferior vena cava.
Peripheric tumours with extension into the inferior vena cava pose difficult management problems. Venovenous bypass using a centrifugal pump to decompress the inferior vena cava may be useful adjunct during vascular isolation of the tumour. We have modified the technique by adding portal decompression to avoid visceral accumulation of toxic metabolites. We have used this technique in two patients who had intracaval extension of tumours, one renal and one adrenal carcinoma.
Adenocarcinoma↗
Integrating undergraduate and postgraduate education in general practice: experience in Tayside.
Several forces have resulted in the creation in Tayside of the first formally integrated unit of undergraduate and postgraduate education in general practice in the United Kingdom. Forces that helped this integration included the desire for change, national developments in education, financial support through funds set aside to cover the additional cost of teaching, and a management structure which concentrates on shared leadership. Forces that hindered the integration included uneasiness about ideas for reforming traditional structures, institutional inertia, the complexity of financial arrangements, and tensions over priorities. The experience of managing institutional changes in Tayside has been invaluable and will lead to a more cohesive approach to undergraduate teaching, postgraduate training, and the provision of services relevant to the development of general practice.
Curriculum↗
C-erbB-2 gene amplification: a molecular marker in recurrent bladder tumors?
C-erbB-2 gene amplification and protein overexpression have been implicated as prognostic markers for patients with recurrent progressive bladder tumors. This event has been investigated as a potential diagnostic indicator in archival samples of transitional cell carcinoma of the bladder. Two hundred thirty-six bladder tumors from 89 patients with recurrent disease (mean follow-up, 4 years), 20 tumors from patients with no evidence of bladder tumor recurrence (mean follow-up, 7 years) and 10 normal bladder controls (patients with no history of transitional cell carcinoma) were studied. A differential PCR was used to provide a semiquantitative estimate of C-erbB-2 gene amplification. Protein overexpression was assessed immunohistochemically. Sixteen of 89 patients with recurrent disease had evidence of C-erbB-2 gene amplification. No C-erbB-2 gene amplification was seen in the nonrecurrent tumors or normal bladder controls. Of the 89 patients with recurrent bladder tumors, 43 had evidence of progressive disease, and of these, 14 patients exhibited C-erbB-2 gene amplification, indicating a strong association with gene amplification and progressive disease (P < 0.0005). Gene amplification in these patients was seen only after disease progression had occurred. Protein overexpression was seen in 50% of patients with recurrent and 45% of patients with nonrecurrent disease. No protein overexpression was seen in normal controls. Protein overexpression could not be linked to disease progression. C-erbB-2 gene amplification and protein overexpression were of predictive value in multivariate analysis for overall bladder cancer death; however stage and grade remained the most important independent prognostic variables. C-erbB-2 gene amplification and protein overexpression were of no value as independent markers for the prediction of disease recurrence or progression. It appears from these results that the role of C-erbB-2 as a diagnostic marker may far outweigh its usefulness as a prognostic indicator.
Aged↗
Brassica napus pollen oleosins possess a characteristic C-terminal domain.
The sequences of Brassica napus L. pollen oleosins have been determined and examined. Contrary to a recent report, inferred primary sequences of pollen oleosins do include a unique C-terminal domain characterised by the presence of a repetitive motif of three alanine and one proline residue (AAAP). This motif appears to be present in all oleosins expressed in pollen, but not in oleosins from other tissues.
Amino Acid Sequence↗
Comparison of the T helper cell response induced by respiratory syncytial virus and its fusion protein in BALB/c mice.
Specific proliferative T-cell responses were induced in the lymph node cells (LNC) of mice immunised with a sucrose density gradient purified preparation of respiratory syncytial (RS) virus or an immunoaffinity purified preparation of the F glycoprotein. Inhibition studies and flow cytometric analysis showed that the responding cell population were CD4+ T cells. The cytokines produced by virus-specific and F-specific cells were assessed using the CTLL cell line. Peak quantities of cytokine were consistently detected in the supernatants of stimulated cultures 24 h prior to maximum proliferation. The proportion of IL-2 released was determined by blocking IL-2 activity with an anti-IL-2 monoclonal antibody. In cultures of RS virus primed LNC challenged with whole virus there was a switch of cytokine production from 70% IL-2 at day 3 to 80% IL-4 by 6 days of culture. In contrast, LNC cultures from mice immunised with F protein secreted 75-100% IL-2 throughout the culture period. These data suggest that after 6 days of challenge with viral antigen, the RS virus-primed LNC response consists of T helper cells which are predominantly of the Th2 subset, secreting IL-4, whilst F protein-primed LNC secrete large quantities of IL-2 and can therefore be classified as predominantly of the Th1 subset.
Animals↗