Biomedical subjects
K Collins
Publications and source records attributed to K Collins.
Mapping the difficulties experienced by clinicians and managers in health and social care who are seeking to develop research skills.
In 1994 the Department of Health commissioned project work and reviews to inform the development of a National Strategy to enhance the capacity of the NHS workforce to contribute to Research and Development. This paper reports one aspect of this review: a preliminary study mapping the difficulties experienced by clinicians and managers who sought to develop their research skills. A range of professionals were included in the sample, all of whom had applied for funding to undertake research education or training through a variety of schemes offering differing levels of support. There was a remarkable degree of consistency between the professional groups in terms of their level of training, success in achieving funding and their perception of the difficulties they faced in pursuing funding for research training--which they ranked in the same order of importance. However, two major significant differences arose: nurses and therapists rated their managers as less helpful, and they felt that completing application forms for research training was a skill that they lacked. The ranking of areas of difficulty, and the additional comments made by all respondents highlight issues that need to be addressed within a coherent strategic framework to reduce the difficulties experienced by those professionals wishing to pursue funding for research training.
Everyday problem solving in elderly women: contributions of residence, perceived control, and age.
This study examined the use of relativistic operations in everyday problem solving by elderly women. Thirty-two community residents and 32 nursing hostel residents aged between 65-90 years participated. Structured interviews canvassed the role of residence and other factors thought to contribute to the maintenance of problem-solving skills. Path analysis was used to test the developed model of the influences of age, engagement in problem-solving activities, control orientation, problem familiarity and residence on the use of relativistic operations. Partial support was found for the proposed model. Community residents used significantly more relativistic operations to solve the problems than did hostel residents. A revised model showed that in addition to residence and control orientation, the use of relativistic operations was influenced indirectly by the level of everyday problem-solving activity, through the orientation of perceived control. Increased problem-solving activity was associated with an internal control orientation, which in turn was directly related to the use of relativistic operations. The influence of age on problem solving was indirect, through problem-solving activity and residence. Our findings provide initial evidence of the extent to which variables other than age can influence everyday problem-solving performance.
National audit of anaesthesia for major abdominal surgery.
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Peer perceptions of aggression and bullying behavior in primary schools in Northern Ireland.
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The Sheffield Centre for Health and Related Research.
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Brush border myosin-I truncated in the motor domain impairs the distribution and the function of endocytic compartments in an hepatoma cell line.
Myosins I, a ubiquitous monomeric class of myosins that exhibits actin-based motor properties, are associated with plasma and/or vesicular membranes and have been suggested as players for trafficking events between cell surface and intracellular membranous structures. To investigate the function of myosins 1, we have transfected a mouse hepatoma cell line (BWTG3) with cDNAs encoding the chicken brush border myosin-I (BBMI) and two variants truncated in the motor domain. One variant is deleted of the first 446 amino acids and thereby lacks the ATP binding site, whereas the other is deleted of the entire motor domain and lacks the ATP and actin binding sites. We have observed (i) that significant amounts of the truncated variants are recovered with membrane fractions after cell fractionation, (ii) that they codistribute with a compartment containing alpha2-macroglobulin internalized for 30 min as determined by fluorescent microscopy, (iii) that the production of BBMI-truncated variants impairs the distribution of the acidic compartment and ligands internalized for 30 min, and (iv) that the production of the truncated variant containing the actin binding site decreases the rate of alpha2-macroglobulin degradation whereas the production of the variant lacking the ATP binding site and the actin binding site increases the rate of a2-macroglobulin degradation. These observations indicate that the two truncated variants have a dominant negative effect on the distribution and the function of the endocytic compartments. We propose that an unidentified myosin-I might contribute to the distribution of endocytic compartments in a juxtanuclear position and/or to the regulation of the delivery of ligands to the degradative compartment in BWTG3 cells.
Structure and function of telomerase.
The study of eukaryotic telomeres at the molecular level began with the discovery of short, tandem repeats at Tetrahymena chromosome ends. In the following two decades, major insights about telomere structure and function have come from investigations of telomerase, the DNA polymerase that synthesizes these repeats. In the past year, three areas of telomerase research have been particularly intense: assays of telomerase activity, isolation of telomerase components, and studies of the regulation of telomerase and telomere length in vivo.
Leukocyte esterase dipstick as a rapid screening test for vaginitis and cervicitis.
STUDY OBJECTIVE: To assess the ability of vaginal and cervical leukocyte esterase (LE) dipstick to detect vaginitis and cervicitis. DESIGN: A prospective, cross-sectional study to assess the ability of the LE dipstick of vaginal secretions to detect trichomonads, candida, and bacterial vaginosis and the LE dipstick of vaginal and cervical secretions to detect gonococcal and chlamydia infection and polymorphonuclear cells (PMNs). SETTING: An inner-city shelter facility clinic. PARTICIPANTS: 183 sexually active, nonmenstruating females aged 13-21 years (Mean = 17.7, SD = 1.98 years): 47% black, 40% white, and 11% Hispanic. OUTCOME MEASURES: Sensitivity (SN), specificity (SP), positive and negative predictive values (PVP, PVN), with 95% confidence intervals, of vaginal and cervical LE dipstick > or = trace in detecting vaginal and cervical infections. RESULTS: A positive vaginal LE had a moderately high SN and PVN but poor SP and PVP in detecting trichomonas and candida vaginitis and bacterial vaginosis. A positive vaginal and cervical LE had a high SN and PVN but poor SP and PVP in detecting gonorrhea and chlamydia infection. A positive cervical LE had a moderate SN and low SP in detecting PMNs on Gram stain. CONCLUSIONS: The LE dipstick of vaginal and cervical secretions was only a moderately good screening test for vaginal infection but a good screening test for cervical infection.
Decreased interleukin-2 production in murine acute pancreatitis: potential for immunomodulation.
BACKGROUND & AIMS: The role of the cytokine interleukin 2 (IL-2) has long been recognized as central to normal immunologic function and defense against infection after burns and trauma, but little effort has been directed towards its role in acute pancreatitis (AP), which also has a high mortality related to sepsis. This study investigated the potential role of IL-2 in mice with diet-induced AP. METHODS: AP was induced in mice by 10 days of feeding a choline-deficient, ethionine-supplemented diet. T-helper (CD4) cells were estimated, and T-cell mitogen-stimulated splenocyte proliferation and IL-2 production in vitro were measured on days 3, 7, and 10. RESULTS: Significant reduction in IL-2 production was found on day 3 (32%; P < 0.05) and day 10 (48%; P < 0.005). Administration of intraperitoneal lipopolysaccharide on day 10 was associated with reduced IL-2 production (P < 0.025) 4 hours later and 90% mortality in animals with AP. In vivo therapy with recombinant IL-2 improved in vitro IL-2 secretion (P < 0.05) and reduced lipopolysaccharide-induced mortality (P = 0.036). CONCLUSIONS: Murine diet-induced AP is associated with impaired immune function and increased susceptibility to sepsis and may be a valuable tool in the investigation of immunomodulation in AP.
Utilization of ribonucleotides and RNA primers by Tetrahymena telomerase.
Telomerase is a ribonucleoprotein (RNP) DNA polymerase involved in telomere synthesis. A short sequence within the telomerase RNA component provides a template for de novo addition of the G-rich strand of a telomeric simple sequence repeat onto chromosome termini. In vitro, telomerase can elongate single-stranded DNA primers processively: one primer can be extended by multiple rounds of template copying before product dissociation. Telomerase will incorporate dNTPs or ddNTPs and will elongate any G-rich, single-stranded primer DNA. In this report, we show that Tetrahymena telomerase was able to incorporate a ribonucleotide, rGTP, into product polynucleotide. Synthesis of the product [d(TT)r(GGGG)]n was processive, suggesting that the chimeric product remained associated with the enzyme both at the active site and at a second, previously characterized, template-independent product binding site. As predicted by this finding, RNA-containing oligonucleotides served as primers for elongation. More than 3 nt of RNA at a primer 3' end decreased the quantity of product synthesis but increased the affinity of the primer for telomerase. Thus, RNA-containing primers were effective as competitive inhibitors of DNA primer elongation by telomerase. These results support the possible evolutionary origin of telomerase as an RNA-dependent RNA polymerase.
Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy.
OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) in an outbreak among patients receiving home intravenous infusion therapy. DESIGN: Case-control and retrospective cohort studies. SETTING: Home health agency. PATIENTS: Patients receiving home intravenous infusion therapy from Rhode Island Home Therapeutics (RIHT) from January through December 1993. MAIN OUTCOME MEASURE: Development of primary BSI. METHODS: We compared patients with BSI (ie, case patients) with randomly selected noninfected RIHT patients receiving intravenous therapy, conducted a cohort study of all RIHT patients receiving intravenous therapy via a central venous catheter (CVC), and conducted a culture survey of injection cap luminal fluid. RESULTS: Case patients were more likely than controls to have had therapy via a CVC (11/11 vs 14/32; odds ratio [OR] undefined; P < .001) or total parenteral nutrition and intralipid therapy (TPN/IL) (9/11 vs 3/32; OR, 43.5; 95% confidence interval [CI], 4.9 to 510.0). Among RIHT patients with CVCs, risk factors for BSI were receipt of TPN/IL (9/35 vs 2/67; rate ratio [RR], 8.6; 95% CI, 2.0 to 37.7) or use of a needleless infusion system (10/41 vs 1/61; RR, 14.9; 95% CI, 2.0 to 111.8). Only the combination of both exposures was significantly associated with development of a BSI (P < .001). Luminal fluid from injection caps of needleless devices was significantly more likely to be culture positive than fluid from protected-needle devices (5/23 vs 0/18; RR undefined; P = .04). CONCLUSIONS: Our data suggest that a needleless device used for TPN/IL was associated with increased risk of BSI when injection caps were changed every 7 days.
Purification of Tetrahymena telomerase and cloning of genes encoding the two protein components of the enzyme.
Telomerase is a ribonucleoprotein DNA polymerase that catalyzes the de novo synthesis of telomeric simple sequence repeats. We describe the purification of telomerase and the cloning of cDNAs encoding two protein subunits from the ciliate Tetrahymena. Two proteins of 80 and 95 kDa copurified and coimmunoprecipitated with telomerase activity and the previously identified Tetrahymena telomerase RNA. The p95 subunit specifically cross-linked to a radiolabeled telomeric DNA primer, while the p80 subunit specifically bound to radiolabeled telomerase RNA. At the primary sequence level, the two telomerase proteins share only limited homologies with other polymerases and polymerase accessory factors.
Interleukin-2 receptor expression and function following thermal injury.
BACKGROUND/OBJECTIVE: Serious traumatic or thermal injury is associated with depression of cellular immunity, including the failure of T-lymphocyte proliferation in response to stimulation that depends both on production of interleukin-2 (IL-2) and on expression of functional IL-2 receptors (IL-2R). While decreased IL-2 production following thermal injury is undisputed, the status of IL-2R expression and function in this setting is controversial; therefore, we sought to investigate this issue. DESIGN: A total of 220 male A/J mice (n = 22 per group) were subjected to a 20% scald burn injury or sham burn, killed 4, 7, 10, 14, or 21 days later, and splenocytes harvested. In vitro parameters of both IL-2R expression and function were measured. RESULTS: On day 7, splenic lymphocyte proliferation and IL-2 production in response to mitogenic stimulation were both suppressed following burn injury to 50% and 60% of controls, respectively. Northern blot analysis revealed normal IL-2R p55 messenger RNA expression in response to mitogenic stimulation on days 7, 10, and 14 in thermally injured animals. Phenotypic IL-2R p55 expression in concanavalin A-stimulated CD3+ cells was unchanged following burn injury. Binding of fluorescein-labeled IL-2 to cell membranes was increased in burned animals at days 10 and 14. The addition of IL-2 to cultures of spleen cells from burned mice consistently restored the mitogenic response to that of the controls. CONCLUSIONS: Thermal injury in this model does not result in either quantitative or functional suppression of IL-2R. Suppression of T-cell activation and proliferation, seen following thermal injury, appears primarily related to abnormal IL-2 production.
Granulocyte-macrophage colony-stimulating factor modulates immune function and improves survival after experimental thermal injury.
Thermal injury is associated with reduced colony-stimulating activity, which correlates with increased susceptibility to infection. To assess the effect of therapeutic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent body surface burn or a sham burn. Animals were subsequently treated with either vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10 after injury. Survival was significantly better in animals treated with 200 ng GM-CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation and interleukin (IL) 2 production were significantly depressed after burn injury. In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in both of these parameters of T cell function. These data suggest that GM-CSF has a potential therapeutic role in the prevention of death from burn sepsis and appears to act, at least in part, by restoring defective T cell proliferation and IL-2 production.
Recombinant expression of the brush border myosin I heavy chain.
Although the specific functions of myosin I motors are not known, their localization to membrane structures suggests a function in membrane motility. Different myosin I isoforms in the same cell or in different cells can possess different localizations. To determine if the localization and biochemical activity of the best-characterized mammalian myosin I, chicken intestinal epithelium brush border myosin I, was dependent on determinants of the membrane or actin cytoskeleton specific to epithelial cells, we transfected the cDNA for the heavy chain of this myosin into COS cells. Transient transfection of COS cells with the chicken brush border myosin heavy chain resulted in the production of recombinant myosin I. Recombinant brush border myosin I localized to protrusions of the plasma membrane, particularly at spreading edges, and also to unknown cytoplasmic structures. Some cells expressing particularly high levels of brush border myosin I possessed a highly irregular surface. Recombinant brush border myosin I purified from COS cells bound to actin filaments in an ATP-dependent manner and decorated actin filaments to form a characteristic appearance. The recombinant myosin also catalyzed calcium-sensitive, actin-activated MgATPase activity similar to that of the native enzyme. Thus, any cellular factor required for the general membrane localization or biochemical activity of brush border myosin I is present in COS cells as well as intestinal epithelium.
Long-term immunotherapeutic intervention with pentoxifylline in a mouse model of thermal injury and infection.
Major thermal or traumatic injury often results in abnormalities of immune function, and these abnormalities contribute to the increased susceptibility to infection observed in these patients. Abnormalities of T-cell function, including decreased proliferation and secretion of cytokines are observed following major injury and, conversely, there is markedly increased monokine production. Thus, therapy of this syndrome might logically be aimed at modulating the immune system to upregulate T-cell function and downregulate monocyte hyperactivation. Pentoxifylline (PTX), a methylxanthine derivative, has been shown to be therapeutically effective in several animal models. The purpose of this study was to evaluate PTX and its effect on cytokine production in a mouse model of thermal injury and to study its effect on survival after septic challenge. The results show that PTX therapy after injury can restore T-cell production of IL-2 and downregulate the hyperactive macrophage secretion of proinflammatory cytokines. However, improvement in survival resulting from this therapy following thermal injury and septic challenge depends on timing of dosage.
Orthodoxy and reform: differing medical practices in a Glasgow Jewish Victorian family.
Medical botanists formed a major and growing element in the delivery of medical care in Victorian Britain, supplementing the provision made by qualified physicians. Medical reform, introduced into Britain from the United States in the middle of the nineteenth century, combined botanical treatment, including a strong emphasis on the use of lobelia, with physiotherapy. The Levenston family in Glasgow was represented among both qualified orthodox medical practitioners and unqualified practitioners of medical botany. Samuel Levenston graduated M.D. at the University of Glasgow in 1859 and had a long career in medical practice in Glasgow after years of work as an unqualified practitioner. His father and brothers were active in medical botany in Glasgow, Edinburgh and Dublin, often posing as doctors but without appropriate qualifications. This paper examines the history of the Levenstons and contrasts the practices of the different members of the family, showing the relationships between a university-trained physician and medical chemists. The surviving Glasgow pharmacopeia of Solomon (Alexander) Levenston illustrates the style of his medical treatments, setting the practice of his medical botany into context.