Search PubMed⌕ Search

Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 109 records · Page 6Linked to original sources
PubMed1997

Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1.

CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1alpha, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption. Although the distribution of mature leukocytes was normal, steady state and induced trafficking and proliferation of myeloid progenitor cells were disordered in -/- mice. Moreover, mature neutrophils from -/- mice failed to chemotax in vitro and failed to mobilize into peripheral blood in vivo in response to MIP-1alpha. Consistent with this, -/- mice had accelerated mortality when challenged with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni eggs intravenously, and observed a 40% reduction in the size of lung granulomas in -/- mice compared to +/+ littermates. This was associated with increased interferon-gamma and decreased interleukin-4 production in -/- versus +/+ lung lymph node cells stimulated with egg-specific antigen, suggesting that CCR1 influences the inflammatory response not only through direct effects on leukocyte chemotaxis, but also through effects on the type 1-type 2 cytokine balance. Thus CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation.

Animals↗
PubMed1997

Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study.

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.

Administration, Inhalation↗
PubMed1997

Macrophage inflammatory protein-1alpha and interferon-inducible protein 10 inhibit synergistically induced growth factor stimulation of MAP kinase activity and suppress phosphorylation of eukaryotic initiation factor 4E and 4E binding protein 1.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Steel factor (SLF) synergistically stimulate Raf-1 kinase activity, protein synthesis, and proliferation in hematopoietic MO7e cells; synergistic action of these factors is blocked by the suppressive chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and interferon-inducible protein 10 (IP-10; Aronica et al, J Biol Chem 270:21998, 1995). We assessed the potential for both stimulatory and inhibitory factors to act through the MAP kinase signaling pathway by studying the effects of growth factors and chemokines on MAP kinase activation. Also, because activation of kinase signaling pathways and stimulation of protein synthesis by peptide growth factors are associated with increased phosphorylation of eukaryotic initiation factor 4E (elF-4E) and the translational repressor 4E-binding protein 1 (4E-BP1) in some target cells, we investigated whether growth factor treatment could alter eIF-4E or 4E-BP1 phosphorylation state in MO7e cells. We report that treatment of MO7e cells with GM-CSF and SLF stimulated significant, greater-than-additive increases in MAP kinase activity and the phosphorylation of both eIF-4E and 4E-BP1. Increased 4E-BP1 phosphorylation correlated with a decrease in the association of 4E-BP1 with eIF-4E. Growth factor-induced phosphorylation of 4E-BP1 and dissociation of 4E-BP1 from eIF-4E was blocked in cells treated with rapamycin, wortmannin, or PD098059. Treatment of cells with IP-10 or MIP-1alpha blocked the stimulatory effects of GM-CSF and SLF, resulting in suppression of MAP kinase activity, eIF-4E and 4E-BP1 phosphorylation, and eIF-4E/4E-BP1 dissociation. Our results suggest that GM-CSF and SLF exert part of their combined growth-promoting effects on MO7e cells through activation of MAP kinase and enhancement of eIF-4E and 4E-BP1 phosphorylation and dissociation and that suppression of growth factor-induced protein synthesis by MIP-1alpha and IP-10 involves translational repression at the level of eIF-4E.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Australian bat lyssavirus infection in three fruit bats from north Queensland.

We report the case findings of Australian bat lyssavirus infection in two black flying foxes (Pteropus alecto) and one little red flying fox (Pteropus scapulatus) from north Queensland between January 1995 and August 1996. Although the P. alecto case in January 1995 is the first recognised case of Australian bat lyssavirus infection in Australia, this was a retrospective diagnosis made after identification of the index case at Ballina in May 1996. Eight persons had exposure to the three bats. Serum antibodies to classical rabies virus were measured in six of these persons; the only one seropositive was a veterinarian who had previously been vaccinated against rabies. Six persons received rabies vaccine following exposure. None of the in-contact humans developed signs of lyssavirus infection. For people exposed to Australian bat lyssavirus-positive bats who have not been scratched or bitten or had mucosal contamination by these bats, we suggest a post-exposure regime of five inoculations of the human diploid cell inactivated rabies vaccine.

Animals↗
PubMed1997

Cloning and characterization of exodus, a novel beta-chemokine.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.

Amino Acid Sequence↗
PubMed1997

Altered hematopoiesis, behavior, and sexual function in mu opioid receptor-deficient mice.

The mu opioid receptor is thought to be the cellular target of opioid narcotics such as morphine and heroin, mediating their effects in both pain relief and euphoria. Its involvement is also implicated in a range of diverse biological processes. Using a mouse model in which the receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in a number of physiological functions. Mice homozygous for the disrupted gene developed normally, but their motor function was altered. Drug-naive homozygotes displayed reduced locomotor activity, and morphine did not induce changes in locomotor activity observed in wild-type mice. Unexpectedly, lack of a functional receptor resulted in changes in both the host defense system and the reproductive system. We observed increased proliferation of granulocyte-macrophage, erythroid, and multipotential progenitor cells in both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which are stress-responsive systems. Unexpected changes in sexual function in male homozygotes were also observed, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results suggest a novel role of the mu opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in pain relief.

Animals↗
PubMed1997

On-line HPLC electrospray mass spectrometry of phosphorothioate oligonucleotide metabolites.

Metabolism of 2'-deoxyphosphorothioate oligonucleotides ISIS 11061 and ISIS 11637 was examined with capillary gel electrophoresis (CGE) and on-line HPLC electrospray mass spectrometry (HPLC/ES-MS). Oligonucleotides were isolated from plasma, liver, and kidneys of rats injected with ISIS 11061 and ISIS 11637. Metabolites found in plasma were consistent with 3'-exonuclease activity. Metabolites isolated from liver and kidney were consistent with 3'- and/or 5'-exonuclease activity. HPLC/ES-MS analysis of ISIS 11061 isolated from kidney indicated extensive degradation from the 3' terminus, but metabolites consistent with 5' degradation and combinations of 3' and 5' truncations also were observed. ISIS 11061 isolated from liver showed less extensive degradation. The 5' truncated metabolites represented the predominant species in contrast to the kidney sample. Metabolites with masses consistent with combinations of 3' and 5' truncations were also observed in liver. The metabolic profiles generated by CGE analysis of these samples agreed qualitatively with mass spectrometric results. HPLC/ES-MS enabled the simultaneous determination of degradation products that are the same length but differ in composition. CGE could discriminate species that differed by one nucleotide in length. HPLC/ES-MS was shown to be a useful tool to study the complex metabolism of antisense oligonucleotides in vivo.

Animals↗
PubMed1997

Behaviour changes in dementia. 1: Point of entry data of a prospective study.

OBJECTIVE: This article analyses behaviour changes in dementia at the point of entry to a longitudinal study. DESIGN: Prospective, longitudinal study of behaviour in dementia, with autopsy follow-up. SETTING: Subjects with dementia, living at home with a carer. All lived in Oxfordshire, UK. PARTICIPANTS: Ninety-seven people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer. MEASURES: At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections covering many different aspects of behaviour. The 121 main questions, with 66 further 'nested' questions, have been shown to have high reliability. RESULTS: This article analyses the types of behaviour change reported by carers at the point of entry to this long-term study. Few correlations were found between behaviour and age, gender and time since onset of dementia. Some types of behaviour were significantly more prevalent in those with greater cognitive impairment. CONCLUSIONS: Many of these changes create problems for carers, for example increased aggressive behaviour, wandering, wakefulness at night, incontinence and persecutory ideas. In general, they are more prevalent in people with more severe dementia.

Aged↗
PubMed1997

Predicting survival, in-hospital cardiac arrests: resuscitation survival variables and training effectiveness.

AIM: the purpose of this study was to determine the key factors influencing survival from cardiopulmonary resuscitation and to analyse the effectiveness of a resuscitation training programme. METHOD: a prospective analysis of all cardiopulmonary resuscitation attempts was performed over a period of 3 years. Included in the study were 808 in hospital cardiac arrests, on whom a full cardiopulmonary resuscitation attempt was performed. Immediate, 24 h and discharge survival rates were the main outcome measures. RESULTS: the immediate survival rate was 43.2%, then 30.2% at 24 h, and 21.9% by discharge. Multivariate analysis of all variables showed that the key factors influencing immediate survival were the 'duration of the arrest', the 'primary arrhythmia', 'basic life support within 3 min of an arrest', 'age less than 70 years', 'the primary mode of arrest-respiratory or cardiac' and 'difficulties with equipment and staff skills during a resuscitation'. Resuscitation training over the 3 year period was shown to have been effective, with improved survival rates on the wards and a reduced number of serious difficulties at arrests. CONCLUSION: data collection and analysis of cardiopulmonary resuscitation attempts are essential for the formulation of survival indicators, and the subsequent training of resuscitation teams.

Aged↗
PubMed1997

A reporter gene assay for fungal sterol biosynthesis inhibitors.

Acetoacetyl-CoA thiolase (ACoAT) catalyses the condensation of two acetyl-CoA molecules, the first step in the sterol biosynthetic pathway. We constructed a yeast strain containing a fusion of the promoter of the Saccharomyces cerevisiae ACoAT gene to a reporter gene (Escherichia coli beta-galactosidase). Reporter gene activity in this strain can be induced by a variety of inhibitors of sterol biosynthesis. These results suggest that the ACoAT gene is feedback regulated at the transcriptional level by products of the sterol biosynthetic pathway. The reporter gene approach described here may be used to screen chemical collections for compounds which inhibit fungal sterol biosynthesis.

Acetyl-CoA C-Acetyltransferase↗
PubMed1997

Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV.

Species-specific differences in the enzymatic inactivation of peptides is an important consideration in the evaluation of therapeutic efficacy. We demonstrate that glucagon-like peptide 2 (GLP-2), shown to be highly intestinotrophic in mice, promotes an increase in intestinal villus height but has no trophic effect on small bowel weight in rats. The reduced intestinotrophic activity of GLP-2 in rats is attributable to inactivation by the enzyme dipeptidyl peptidase IV (DPP-IV). GLP-2(1-33) was degraded to GLP-2(3-33) following incubation with human placental DPP-IV or rat serum but not by serum from DPP-IV-deficient rats. Administration of rat GLP-2 to DPP-IV-deficient rats was associated with markedly increased bioactivity of rat GLP-2 resulting in a significant increase in small bowel weight. A synthetic GLP-2 analog, r[Gly2]GLP-2, with an alanine to glycine substitution at position 2, was resistant to cleavage by both DPP-IV and rat serum in vitro. Treatment of wild-type rats with r[Gly2]GLP-2 produced a statistically significant increase in small bowel mass. DPP-IV-mediated inactivation of GLP-2 is a critical determinant of the growth factor-like properties of GLP-2.

Animals↗
PubMed1997

G1 and S phase gene expression cannot be analyzed in mammalian cells synchronized by inhibition.

Sequence analyses of mRNA from cells arrested with either a G1 phase DNA content or an S phase DNA content were interpreted as indicating that these two cell populations differentially expressed particular transcripts (Earle-Hughes et al. Genome Sci Technol 1, 89-128, 1996). Approximately 13% of the total transcript population appeared to be differentially expressed between the G1 and S phases of the cell cycle. The question arises if it is possible, using inhibition methods (double-thymidine block to produce cells with an S phase DNA content and inhibition with dibutyryl adenosine 3'5'-cyclic monophosphate and theophylline to produce cells with a G1 phase DNA content), to truly synchronize cells and obtain cell populations representative of specific phases of the division cycle. Here it is argued that this is not possible. Cells may have specific amounts of DNA (i.e., G1 phase or S phase DNA content) yet not be representative of these particular phases. It is proposed that the differential gene expression observed may be due to the effects of the inhibitors and does not necessarily reflect the actual transcription pattern in unperturbed cells in specific cell cycle phases. This proposal has a wide applicability and should not be confined to the specific article under discussion.

Animals↗
PubMed1997

A review of educational issues in resuscitation training.

This paper considers a number of concerns about resuscitation training. Poor retention of skills and the factors which affect understanding and memory, as well as the need for a positive attitude towards resuscitation, are discussed. Some specific points are made on how these, as well as the trainer's ability to teach resuscitation, can be improved.

Clinical Competence↗
PubMed1997

HLA class I genotyping by cDNA sequence of a Vietnamese family expressing a weak B46 antigen.

Serological heterogeneity in HLA-B46 antigens has been described. Previous studies have identified B*4601 as the allele encoding the "strong" B46 antigen found in Chinese populations. Serological characterization of a Vietnamese family revealed a "weak" B46 antigen. Complementary DNA for the HLA-A, B and C alleles of three family members were cloned and the coding regions sequenced. The allele encoding the weak B46 antigen has the same coding sequence as B*4601, demonstrating that the antigenic differences are not due to polymorphism in the amino acid sequence of the HLA-B heavy chain. The recently described HLA-B*1525 and HLA-Cw*0403 alleles were also found to segregate in this Vietnamese family.

Alleles↗
PubMed1997

Division pattern of a round mutant of Escherichia coli.

A round mutant of Escherichia coli, when grown in Methocel medium, forms chains of cells and does not form tetrads. This implies that successive division planes of the round mutant are parallel rather than perpendicular. These results differ from a previous proposal that division planes in this round mutant are perpendicular to the prior division plane (W. D. Donachie, S. Addinall, and K. Begg, Bioessays 17:569-576, 1995).

Cell Division↗
PubMed1997

The needs of children whose mothers have HIV infection.

AIM: To ascertain the psychological, social, and educational needs of children born to mothers with HIV infection. METHODS: Review of case records of 120 children and 86 mothers. RESULTS: The cohort of 120 children were born to 92 women, and followed up for a median duration of 48 months (mean (SD) 51.1 (34.1), range 0.3-132). Sixteen children were infected with HIV, 15 were of indeterminate status, and 89 uninfected. Eighty one children (68%) were cared for by their birth mother, of whom 52% were single women and 23 (38% of 61) known to have symptomatic HIV disease. Twenty five mothers of 32 children had died; the child's mean (SD) age at maternal death was 66.9 months (37.7) (range 4-128). Compared with uninfected children, more infected children knew of their mother's diagnosis (31% v 5%) and mothers were also more likely to disclose their own illness to educational authorities (77% v 13%). A larger proportion of infected children had special educational needs (69% v 13%). Only 33 children (28%) were known not to be receiving any support from the voluntary or statutory agencies. CONCLUSION: The results highlight the multiple needs of children living with maternal HIV infection, which require dedicated resources and commitment from health, education, and social work agencies and the voluntary sector. We propose the model of chronic illness as the standard of care for these children.

Adolescent↗
PubMed1997

Trial of two bandaging systems for chronic venous leg ulcers.

A four-layer bandaging system developed at Charing Cross Hospital has been found to be effective in healing chronic venous ulcers but is not available on the Drug Tariff. An alternative system was devised from bandages available on the Drug Tariff and a community-based randomised controlled trial was undertaken to compare the two systems. Twenty-nine patients with a total of 35 ulcerated legs were recruited. Equal numbers of ulcerated legs healed using the two compression systems. Nineteen ulcerated legs did not heal, of which six were withdrawn from the trial-two in the trial system and four in the Charing Cross system. Of the 13 remaining ulcerated legs, for which treatment was completed, the mean reduction in ulcer area was 34% with the trial system and 39% with the Charing Cross system. The change in ulcer area was not statistically significant. However, a much larger trial is required in order to demonstrate definitively that the two bandaging systems are equivalent.

Bandages↗