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Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1999

Injury control strategies: extending the quality and quantity of data relating to road traffic accidents in children.

This review describes how an extended database of information can provide the opportunity to go beyond the traditionally distinct health, engineering, and education initiatives in order to identify the effectiveness of more overarching policies for injury control. Such information can be used to raise awareness and to encourage community participation in designing a road traffic accident prevention strategy.

Accidents, Traffic↗
PubMed1999

Morbidity from asthma in relation to regular treatment: a community based study.

BACKGROUND: The extent to which asthma morbidity in the community occurs in patients who are having relatively little treatment or in those on step 3 or above of the British asthma management guidelines is uncertain. We have looked at this in a community population in southern Nottinghamshire. METHODS: A cross sectional review of treatment in all patients over the age of four with diagnosed asthma was carried out in five large general practices (population 38 865) in 1995/6 using computerised general practice records. The patients' usual treatment was obtained from prescription data and categorised by the appropriate step on the British guidelines on asthma management. Two measures of morbidity, the request for 10 or more short acting beta agonist inhalers a year or the need for a course of oral corticosteroids in the last year, were related to the regular treatment of the patients. RESULTS: Of the 3373 patients (8. 7%) given a diagnosis of asthma, the percentage on steps 1, 2, 3, 4, and 5 of treatment were 54%, 22%, 11%, 3.6%, and 1%, respectively, with a further 8% having had no treatment. During the past year 13. 6% had been prescribed 10 or more beta agonist inhalers and 12.5% had received at least one course of oral corticosteroids. Both measures occurred more frequently in patients taking more prophylactic treatment (step 3 or above). Nevertheless, because most patients were on steps 1 and 2 of the treatment guidelines, more than half the patients requiring high doses of inhaled beta agonists or a course of oral prednisolone came from those taking low dose or no regular inhaled corticosteroid. CONCLUSIONS: Evidence of morbidity from asthma was found in many patients taking little or no prophylactic medication and this should be amenable to improved education. A different approach may be needed for patients with continuing morbidity who are already taking higher doses of prophylactic medication.

Adolescent↗
PubMed1999

Altered responsiveness to chemokines due to targeted disruption of SHIP.

SHIP has been implicated in negative signaling in a number of hematopoietic cell types and is postulated to downregulate phosphatidylinositol-3-kinase- (PI-3K-) initiated events in diverse receptor signaling pathways. Because PI-3K is implicated in chemokine signaling, we investigated whether SHIP plays any role in cellular responses to chemokines. We found that a number of immature and mature hematopoietic cells from SHIP-deficient mice manifested enhanced directional migration (chemotaxis) in response to the chemokines stromal cell-derived factor-1 (SDF-1) and B-lymphocyte chemoattractant (BLC). SHIP(-/-) cells were also more active in calcium influx and actin polymerization in response to SDF-1. However, colony formation by SHIP-deficient hematopoietic progenitor cell (HPCs) was not inhibited by 13 myelosuppressive chemokines that normally inhibit proliferation of HPCs. These altered biologic activities of chemokines on SHIP-deficient cells are not caused by simple modulation of chemokine receptor expression in SHIP-deficient mice, implicating SHIP in the modulation of chemokine-induced signaling and downstream effects.

Actins↗
PubMed1999

Pharmacokinetic and pharmacodynamic action of etodolac in patients after oral surgery.

The objective of this double-blind, randomized, parallel-group study was to evaluate the pharmacokinetics of etodolac and the pharmacodynamic response of pain in patients following oral surgery who had received 200 or 400 mg of etodolac immediate release (IR), 400 or 1200 mg of etodolac extended release (ER), or a placebo. Etodolac concentrations in 441 plasma samples from 187 patients were analyzed for population pharmacokinetics using the NONMEM program. A one-compartment pharmacokinetic model with first-order absorption described the observed data. For etodolac IR, the population mean (%CV) estimates were 3.01 L/h (5.3%) for clearance, 13.6 L (6.8%) for volume of distribution, and 2.31 h-1 (33%) for ka. Respective values for etodolac ER were 3.68 L/h (11%) for clearance, 24.3 L (22%) for volume of distribution, and 0.172 h-1 (24%) for ka. These values generally agreed with previously reported values in healthy adults. Pharmacodynamic assessments included collection of a four-level categorical rating of pain intensity for up to 24 hours after treatment. Pain intensity difference scores were temporally related to etodolac concentrations and were described using an indirect response model. Mean (%CV) pharmacodynamic parameters were IC50 of 14.0 mg/L (9.5%), kout of 1.62 h-1 (13%), FR of 0.56 (8.2%), and Hill coefficients that ranged from 1.26 to 3.34 units. A single 1200 mg dose of etodolac ER given once daily was shown to provide substantial efficacy for 13 hours after dose, modest effect through 24 hours, and a more sustained duration of action than the IR dosage form.

Adolescent↗
PubMed1999

A pilot study of expiratory flow limitation and lung volume reduction surgery.

STUDY OBJECTIVES: To examine the relationships between changes in expiratory flow limitation (FL) during anesthesia and postoperative responses to lung volume reduction surgery (LVRS). DESIGN: Prospective consecutive case comparison. SETTING: University medical center. PATIENTS: Eight patients with severe emphysema. INTERVENTIONS: General anesthesia with muscle paralysis and thoracic epidural analgesia were provided for LVRS via median sternotomy. MEASUREMENTS: FEV(1), functional residual capacity (FRC), and total lung capacity (TLC) were measured preoperatively and 3 months postoperatively. Tidal volume (VT) flow/volume (F/V) curves were obtained with a Pitot-type spirometer. VT, expiratory flow rate at 0. 25 x VT (V'VT,25% ), and peak expiratory flow rate (V'VT,MAX) were obtained from VT F/V curves to derive V'VT,25%/V'VT,MAX ratio as a measure of FL. RESULTS: Closed chest VT F/V curves during anesthesia pre-LVRS showed four patients with FL (group A) whose V'VT,25%/V'VT, MAX ratio was 0.38 +/- 0.06 (mean +/- SD) and four patients without FL (group B) whose V'VT,25%/V'VT,MAX ratio was 0.82 +/- 0.06 (p = 0. 0001). Closed chest post-LVRS V'VT,25%/V'VT,MAX ratio during anesthesia increased by 0.48 +/- 0.08 in group A, compared with a 0. 19 +/- 0.16 reduction in group B (p = 0.0001). Preoperative FEV(1) was 0.57 +/- 0.10 L for group A vs 0.82 +/- 0.13 L for group B (p = 0.02). Postoperative FEV(1) increased by 67 +/- 40% for group A (p = 0.03) vs 29 +/- 21% for group B (not significant). FRC decreased by 33 +/- 3% for group A vs 17 +/- 5% for group B (p = 0.0007), and FRC/TLC decreased by 0.14 +/- 0.05 for group A vs 0.01 +/- 0.07 for group B (p = 0.026). Post-LVRS V'VT,25%/V'VT,MAX ratio change during anesthesia correlated with postoperative reduction in FRC (r(2) = 0. 89, p = 0.0004) and FRC/TLC (r(2) = 0.52, p = 0.045). CONCLUSION: Post-LVRS change in V'VT,25%/V'VT,MAX ratio during anesthesia showed a linear relationship with 3-month postoperative improvement in dynamic hyperinflation. Thus, V'VT,25%/V'VT,MAX ratio may help provide valuable insights into the interactions between chest wall recoil, dynamic hyperinflation, and VT flow rates in patients with severe COPD and LVRS.

Aged↗
PubMed1999

Sequential consequences of therapists' interventions.

Using sequential analysis, the authors examined how therapists' actions related to the verbal disclosure and defensive patterns that followed therapists' interventions within a single therapy hour for 20 patients. At the same time, a new measure, the Psychodynamic Intervention Rating Scale (PIRS), was tested for reliability and construct validity. Results indicated that therapists fit their styles of intervention to patients' levels of distress and functioning. Within the session, patient's emotional elaboration was followed by therapist's defense interpretation, followed by more patient emotional elaboration. Patient elaboration of significance was followed by more transference interpretation, followed by more patient elaboration of significance. Noninterpretive interventions were followed by patient's disclosure of facts, not emotion. Both interpretive intervention process sequences and therapist's use of support predicted posttreatment symptom reduction. The PIRS was shown to have satisfactory reliability and construct validity.

Depressive Disorder↗
PubMed1999

Public-private partnerships: working at the local level to increase the quality and number of medical homes for Medicaid children.

We have described a process in which one state's public health leaders provided a large degree of flexibility at the community level to improve pediatric health care access for children in need. This "room-to-wiggle" allowed program providers to tailor their programs to the specific needs of their communities while remaining faithful to the statewide goals. Among the most promising outcomes of the coordinated efforts to forge public-private partnerships is the continuation of the relationships that developed in the process and the further collaborations they have spawned.

Child↗
PubMed1998

Interaction of p59fyn kinase with the dynein light chain, Tctex-1, and colocalization during cytokinesis.

The protein tyrosine kinase p59fyn (Fyn) plays important roles in both lymphocyte Ag receptor signaling and cytokinesis of proB cells. We utilized yeast two-hybrid cloning to identify the product of the tctex-1 gene as a protein that specifically interacts with Fyn, but not with other Src family kinases. Tctex-1 was recently identified as a component of the dynein cytoskeletal motor complex. The capacity of a Tctex-1-glutathione S-transferase fusion protein to effectively bind Fyn from cell lysates confirmed the authenticity of this interaction. Tctex-1 binding required the first 19 amino acids of Fyn and integrity of two lysine residues within this sequence that were previously shown to be important for Fyn interactions with the immunoreceptor tyrosine-based activation motifs (ITAMs) of lymphocyte Ag receptors. Expression of tctex-1 mRNA and protein was observed in all lymphoma lines analyzed, and immunofluorescence confocal microscopy localized the protein to the perinuclear region. Analysis of a T cell hybridoma revealed prominent colocalization of Tctex-1 and Fyn at the cleavage furrow and mitotic spindles in cells undergoing cytokinesis. Our results provide a unique insight into a mechanism by which Tctex-1 might mediate specific recruitment of Fyn to the dynein complex in lymphocytes, which may be a critical event in mediating the previously defined role of Fyn in cytokinesis.

Animals↗
PubMed1998

Cycle-specific replication of chromosomal and F-plasmid origins.

There have been various proposals for the pattern of F-plasmid replication during the division cycle. Here we show that the recent studies of Gordon et al. (Cell 90, 1113-1121, 1997) on the duplication and segregation of green fluorescent protein (GFP) labeled replication origins of the Escherichia coli chromosome and the F plasmid during the division cycle support the proposal that the F plasmid replicates with a cell-cycle-specific (artiocyclic) pattern.

Cell Cycle↗
PubMed1998

Multiple inhibitory cytokines induce deregulated progenitor growth and apoptosis in hematopoietic cells from Fac-/- mice.

We used a murine model containing a disruption of the murine homologue (Fac) of Fanconi Anemia group C (FAC) to evaluate the role of Fac in the pathogenesis of bone marrow (BM) failure. Methylcellulose cultures of BM cells from Fac-/- and Fac+/+ mice were established to examine the growth of multipotent and lineage-restricted progenitors containing inhibitory cytokines, including interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-1alpha (MIP-1alpha). Clonogenic growth of Fac-/- progenitors was reduced by 50% at 50- to 100-fold lower concentrations of all inhibitory cytokines evaluated. We hypothesized that the aberrant responsiveness to inhibitory cytokines in clonogenic cells may be a result of deregulated apoptosis. To test this hypothesis, we performed the TUNEL assay on purified populations of primary BM cells enriched for hematopoietic progenitors or differentiated myeloid cells. After stimulation with TNF-alpha, accentuated apoptosis was observed in both populations of Fac-/- cells. In addition, deregulated apoptosis was also noted in the most immature phenotypic population of hematopoietic cells after stimulation with MIP-1alpha. Together these data suggest a role of Fac in affecting the signaling of multiple cytokine pathways and support cytokine-mediated apoptosis as a major mechanism responsible for BM failure observed in FA patients.

Animals↗
PubMed1998

Characterization of CKbeta8 and CKbeta8-1: two alternatively spliced forms of human beta-chemokine, chemoattractants for neutrophils, monocytes, and lymphocytes, and potent agonists at CC chemokine receptor 1.

Two new members of human beta-chemokine cDNA were isolated based on structural and functional similarities to human leukotactin-1. One of these clones was identical to the previously isolated human beta-chemokine, CKbeta8, whereas the other is a splicing variant of CKbeta8, therefore named CKbeta8-1. CKbeta8 was short in 51 nucleotides (17 amino acids) compared with CKbeta8-1. The mature proteins of CKbeta8-1 and CKbeta8 consisted of 116 and 99 amino acids with calculated molecular weights of 12,500 and 10,950, respectively. Both CKbeta8-1 and CKbeta8 were potent agonists at CCR1. These chemokines chemoattracted neutrophils, monocytes, and lymphocytes. They also significantly suppressed colony formation by human bone marrow, granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. To our knowledge, this is the first example that an alternative splicing produces two active beta-chemokines from a single gene.

Alternative Splicing↗
PubMed1998

On the interpretation of the shortening of the G1-phase by overexpression of cyclins in mammalian cells.

Increasing the concentration of cyclins in mammalian cells leads to a shortening of the G1-phase of the division cycle. This observation has been interpreted as indicating that these cyclins act during, and are rate limiting for, passage through the G1-phase. Here it is argued that it is not possible to interpret experiments involving cyclin overexpression-induced changes in the lengths of individual cell cycle phases without considering changes in the overall cellular growth rate. A rigorous reanalysis of these experiments demonstrates that the results are consistent with the proposal that the shortening of the G1-phase is merely due to an increase in the rate of mass synthesis in all phases of the cell cycle. Increased cyclin concentrations leads to a faster rate of mass synthesis and a concomitant shortening of the G1-phase. Cyclins can also affect the length of the S- and G2-phases, which leads to the observed shortening of the G1-phase. Thus, the experiments on cyclin overexpression and their effect on G1-phase length cannot be used to support the proposal that cyclins act specifically during the G1-phase of the division cycle.

Animals↗
PubMed1998

A positive effect of p21cip1/waf1 in the colony formation from murine myeloid progenitor cells as assessed by retroviral-mediated gene transfer.

p21cip1/waf1 is a cyclin dependent kinase inhibitor. We have previously reported stimulation of p21cip1/waf1 by steel factor and GM-CSF in a factor dependent cell line and of p21cip1/waf1 involvement in hematopoiesis in vivo in p21cip1/waf1 gene knockout (-/-) mice. To further assess a role for increased p21cip1/waf1 in hematopoietic progenitor cells, we developed the retroviral vector L(p21cip1)SN to transcriptionally regulate p21cip1/waf1 from the Mo-MLV LTR. L(p21cip1)SN and the control vector LXSN were used to transduce murine bone marrow progenitor cells from p21cip1/waf1 (-/-) and littermate control (+/+) mice, as well as from other mouse strains. Hematopoietic colony formation by transduced cells was assessed in semi-solid culture medium with multiple growth factors. Myeloid colony formation by bone marrow cells from p21cip1/waf1 (-/-) mice was significantly lower than that by (+/+) mouse cells. Transduction of cells with LXSN had no effect on colony formation: however, (-/-) cells transduced with L(p21cip1)SN formed significantly greater numbers of colonies than either LXSN-transduced (-/-) or (+/-) cells. Moreover, L(p21cip1)SN-transduced (+/+) cells formed significantly more colonies than LXSN-transduced (+/+) cells. Increased cloning efficiency of progenitors from normal strains of mice induced by L(p21cip1)SN compared to LXSN-transduced cells was seen whether unseparated or highly purified populations of Sca1+ Lin- marrow cells were used. Gene transfer of L(p21cip1)SN increased the size and number of cells per colony, as well as the number of colonies compared to LXSN gene transfer. No colonies grew from non-transduced, LXSN-, or L(p21cip1)SN-transduced cells when no growth factors were added to the cultures. These results document the positive effect of p21cip1/waf1 in the proliferation and/or differentiation of the murine myeloid progenitor cells that lead to colony formation.

Animals↗
PubMed1998

A major histocompatibility complex class I allele shared by two species of chimpanzee.

Little is known regarding the rates at which natural selection can modify or retain antigen presenting alleles at the major histocompatibility complex (MHC). Discovery of identical [1101 base pairs (bp)] coding regions at the MHC class I C locus in Pan troglodytes and Pan paniscus, chimpanzee species that diverged approximately 2.3 million years ago, now indicates that a class I allotype can survive for at least this period. Remarkable conservation was also reflected in the (1799 bp) introns where a maximum of only six substitutions distinguished five alleles (three from P. troglodytes and two from P. paniscus) that encoded the identical heavy chain allotype. Analysis of a more distantly related human allele, HLA-Cw*0702, corroborated that intron variation was non-uniform along the gene. Thus we provide a clear reference frame for the lifetime of an MHC class I allotype, a direct estimate of allelic substitution rates, and evidence for an unusual evolution of MHC class I introns.

Alleles↗
PubMed1998

Mammalian cells are not synchronized in G1-phase by starvation or inhibition: considerations of the fundamental concept of G1-phase synchronization.

Synchronization of mammalian cells by starvation-refeeding or by inhibition-release are among the most commonly used techniques for division cycle analysis. An alternative analysis--in the form of a Gedanken or thought experiment--is presented, casting doubt on the utility of this synchronization method. Arresting cell growth produces a culture where all cells contain a G1 amount of DNA. However, these cells are not arrested at a particular point in the G1-phase. Analysis of 'G1 arrested cells' suggests that, upon resumption of growth, the cells are not synchronized.

3T3 Cells↗