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Biomedical subjects

K Edwards

Publications and source records attributed to K Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1999

Phase II trial of 5-fluorouracil, folinic acid and recombinant alpha-2a-interferon in patients with advanced colorectal cancer.

A clinical trial regimen modulating 5-fluorouracil (5-FU) with both folinic acid (FA) and recombinant alpha-2a-interferon (ralpha-2a-IFN) was noted to have a response rate of 54% and median survival of 16.3 months (Grem et al., J Clin Oncol 1993, 11: 1737-45). Reported herein is a phase II trial performed to further examine this regimen in metastatic colorectal cancer. Fifty-one patients with histologically proven, measurable advanced colorectal cancer with no prior therapy for metastatic disease were enrolled. ralpha-2a-IFN, 5 MIU/m2/day was given s.c. on days 1-7. FA, 500 mg/m2/day, and 5-FU, 370 mg/m2/day, were given i.v. on days 2-6. Cycles were repeated at 3 week intervals. Three complete and 12 partial responses were observed for an overall response rate of 29% (95% confidence interval: 18-45%). The median time to treatment failure and median survival were 4.6 and 15.5 months, respectively. Dose-limiting toxicities encountered were gastrointestinal, and included diarrhea, stomatitis, nausea and vomiting. These results do not support the concept of using concurrent ralpha-2a-IFN and FA as biochemical modulators of 5-FU. We observed increased toxicity and similar efficacy compared to using either modulator separately with 5-FU.

Adult↗
PubMed1999

Mainstream and sidestream cigarette smoke condensates suppress macrophage responsiveness to interferon gamma.

Sidestream smoke evolves from the smoldering end of a cigarette while the smoker is not puffing, and contributes substantially to environmental tobacco smoke (ETS). In contrast, main stream smoke emerges from the butt end of the cigarette and is mainly inhaled by the smoker. This study was performed to compare the effects of short-term exposure to cigarette smoke condensates prepared from sidestream (CSC-SS) and mainstream cigarette smoke (CSC-MS) on macrophage basal metabolism and responsiveness to two different stimuli, bacterial lipopolysaccharide (LPS) and interferon gamma (IFNgamma). Despite their generation at different temperatures and their different chemical composition, CSC - SS and CSC - MS had similar effects on macrophages. Both enhanced macrophage basal metabolism and responsiveness to LPS. Macrophage responsiveness to IFNgamma, assessed by their expression of four functional capacities, was suppressed by both CSC-SS and CSC-MS. The four assessed IFNgamma-inducible functional capacities were: enhanced phagocytosis of immuoglobulin-opsonized sheep red blood cells, TPA-induced peroxide production, class II major histocompatibility complex expression, and nitric oxide synthesis with LPS co-stimulation. The effects of CSC - SS and CSC - MS were similar qualitatively; they differ quantitatively in some cases, with CSC-MS generally effective at lower concentrations (expressed as cigarette-equivalents) than CSC-SS. Considering dilution of sidestream smoke in room air and loss during passage through the respiratory system, we expect to deliver the maximal dose to lung macrophages in situ only in rooms dense with smokers. However, only a fraction of the maximal dose can partially suppress induction of some functions, such as nitric oxide production and MHC expression. Macrophages play critical roles in tissue modeling during development. Of particular concern are neonates, whose organs are still undergoing growth and development, and are therefore susceptible to impaired development. If involuntary exposure to ETS hinders induction of macrophage functional capacities by cytokines, then development of the lungs and perhaps other organs would be impaired. In general, since macrophages are potent effectors and regulators of immunity, impairment of their responsiveness to cytokine must disrupt the proper functioning of the immune system.

Animals↗
PubMed1998

Immunogenicity of pneumococcal vaccine in persons with spinal cord injury.

OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI). DESIGN: Double-blind, randomized, placebo control study. SETTING: SCI unit in a tertiary care medical center and community. PARTICIPANTS: Eighty-seven persons with recent SCI. INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury. MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae. Effects of demographic and injury-related variables on immune response were also evaluated. RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05). Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01). After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values. CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months. Immune response varied according to serotype. Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization.

Adolescent↗
PubMed1998

New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks.

Cholesterol↗
PubMed1998

Effects of PEG-lipids on permeability of phosphatidylcholine/cholesterol liposomes in buffer and in human serum.

The permeability of liposomal membranes was studied as a function of the amount of incorporated PEG-lipid. The fluorescent dyes ethidium, propidium and 5(6)-carboxy fluorescein were used as markers for measurements of spontaneous leakage. The results show that addition of up to 8 mol% of PEG(2000)-DSPE into liposomal membranes of DSPC/Cho and EPC/Cho reduces the permeability of carboxyfluorescein in buffer solution. In contrast, the leakage of the more amphiphilic dye ethidium was not to any measurable extent affected by PEG-lipid inclusion. Another important difference was that ethidum leakage showed a clear dependence on temperature whereas leakage of carboxyfluorescein from pegylated liposomes did not. We conclude that the mechanisms by which the two dyes permeate the liposomal bilayer are qualitatively different. Both ethidium and carboxyfluorescein did interact with human serum components in a way that made measurements in serum unreliable. The more hydrophilic ethidium analogue propidium was shown not to interact with human serum components to any detectable extent. This made propidium suitable for permeability determinations in human serum. It was found that liposomes composed of pure EPC or EPC with 5 mol% DSPE-PEG, displayed a dramatic increase in permeability when subjected to a medium composed of 20% human serum in buffer. Addition of 40 mol% cholesterol to the EPC bilayers reduced the observed release rate in human serum substantially, whereas no stabilizing effect was observed upon PEG-lipid inclusion.

Buffers↗
PubMed1998

Brown-midrib maize (bm1)--a mutation affecting the cinnamyl alcohol dehydrogenase gene.

Brown-midrib (bm) mutants of maize have modified lignin of reddish-brown colour. Although four independent bm loci are known, only one of the mutant genes has been previously identified. We report here that maize bm1, one of the less characterised mutants, shows severely reduced CAD activity in lignified tissues, resulting in the production of a modified lignin. Both the total lignin content and the structure of the polymer are altered by the mutation. We further describe the isolation and characterisation of the maize CAD cDNA and mapping of the CAD gene. CAD maps very closely to the known location of bm1 and co-segregates with the bm1 locus in two independent recombinant inbred populations. These data strongly support the premise that maize bm1 directly affects expression of the CAD gene.

Alcohol Oxidoreductases↗
PubMed1997

Genetic influences on changes in body mass index: a longitudinal analysis of women twins.

Numerous studies have demonstrated genetic influences on body fat, but there also may be genetic effects on its intraindividual variation over time. This study examined changes in body mass index (BMI) using longitudinal data from two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin pairs, with average ages of 41 years and 51 years at the two examinations, respectively. Age-adjusted heritability estimates for the change in BMI over the decade ranged from 0.57 to 0.86 (all p < or = 0.001) using three different statistical analysis approaches, indicating that at least half and possibly as much as 85%+, of the variance in the change in BMI is attributable to genetic influences under a polygenic model. These estimates remained statistically significant after adjusting for environmental factors (ranging from 0.57 to 0.78) and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79), although dizygotic intraclass correlations were low after these adjustments. Thus, in addition to known environmental and behavioral influences, these results provide evidence for genetic influences on changes in BMI over a decade in women.

Adolescent↗
PubMed1997

Control of a trackball by the chin for communication applications, with and without neck movements.

The overall aim was to evaluate whether a trackball could be used for communication by people who cannot speak due to severe motor impairment. The precision of trackball control by isolated jaw movements or a combination of jaw and head movements was evaluated in 18 healthy physical-education students, free of overt symptoms of craniomandibular dysfunction. The participants were asked to operate a trackball using the chin to type a standard text of four short sentences. There were two experimental situations: nine participants performed the typewriting task with their heads fixed; the other nine performed this task with free head movements. Trackball operation moved to the cursor over an alphabetical keyboard displayed on a computer screen and character selection was made by depression of the left-hand click button using the chin. Participants were asked to perform the task as quickly and accurately as possible. Result showed that those with free head movement typed the test significantly faster than those restricted to using only their jaw muscles. The mean time per character selection was 2.4 s (SD 0.3) for the group with free head movement and 2.7 s (SD 0.3) for the group using only jaw muscles. Group scores were not significantly different with regard to accuracy. It is suggested that a chin-operated trackball could be used for communication applications both with and without neck movements.

Adult↗
PubMed1997

Effect of polyethyleneglycol-phospholipids on aggregate structure in preparations of small unilamellar liposomes.

Phospholipids with covalently attached poly(ethylene glycol) (PEG lipids) are commonly used for the preparation of long circulating liposomes. Although it is well known that lipid/PEG-lipid mixed micelles may form above a certain critical concentration of PEG-lipid, little is known about the effects of PEG-lipids on liposome structure and leakage at submicellar concentrations. In this study we have used cryogenic transmission electron microscopy to investigate the effect of PEG(2000)-PE on aggregate structure in preparations of liposomes with different membrane compositions. The results reveal a number of important aggregate structures not documented before. The micrographs show that enclosure of PEG-PE induces the formation of open bilayer discs at concentrations well below those where mixed micelles begin to form. The maximum concentration of PEG-lipid that may be incorporated without alteration of the liposome structure depends on the phospholipid chain length, whereas phospholipid saturation or the presence of cholesterol has little or no effect. The presence of cholesterol does, however, affect the shape of the mixed micelles formed at high concentrations of PEG-lipid. Threadlike micelles form in the absence of cholesterol but adapt a globular shape when cholesterol is present.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Morphological changes induced by phospholipase C and by sphingomyelinase on large unilamellar vesicles: a cryo-transmission electron microscopy study of liposome fusion.

Cryo-transmission electron microscopy has been applied to the study of the changes induced by phospholipase C on large unilamellar vesicles containing phosphatidylcholine, as well as to the action of sphingomyelinase on vesicles containing sphingomyelin. In both cases vesicle aggregation occurs as the earliest detectable phenomenon; later, each system behaves differently. Phospholipase C induces vesicle fusion through an intermediate consisting of aggregated and closely packed vesicles (the "honeycomb structure") that finally transforms into large spherical vesicles. The same honeycomb structure is also observed in the absence of enzyme when diacylglycerols are mixed with the other lipids in organic solution, before hydration. In this case the sample then evolves toward a cubic phase. The fact that the same honeycomb intermediate can lead to vesicle fusion (with enzyme-generated diacylglycerol) or to a cubic phase (when diacylglycerol is premixed with the lipids) is taken in support of the hypothesis according to which a highly curved lipid structure ("stalk") would act as a structural intermediate in membrane fusion. Sphingomyelinase produces complete leakage of vesicle aqueous contents and an increase in size of about one-third of the vesicles. A mechanism of vesicle opening and reassembling is proposed in this case.

Biophysical Phenomena↗
PubMed1997

Illusory recall of vocal affect.

Illusions of memory occur when a person recalls something that did not take place, and may result from processes that systematically bias recall. This paper reports three experiments exploring a novel form of memory bias that can occur when a person is attempting to recall the affective tone of voice in which someone spoke previously. Subjects first studied photographs of faces while listening to sentences spoken in a positive or negative tone of voice. At test, subjects saw brief presentations of faces and were asked to recall the tone of voice in which the pictured person had spoken earlier. Across a variety of study and test conditions a strong recall bias was observed: when faces conveyed either subtle positive or negative affect, subjects tended to recall the pictured person as having spoken with a matching affective tone, regardless of the tone of voice in which the person had actually spoken. It is proposed that this affective recall bias may be the product of a retrieval mechanism that relies on a combination of information from the memory trace and retrieval environment to guide responding.

Adolescent↗
PubMed1997

Heritability of longitudinal changes in coronary-heart-disease risk factors in women twins.

Numerous studies have demonstrated genetic influences on levels of coronary heart disease (CHD) risk factors, but there also may be genetic effects on the intraindividual variation in these risk factors over time. Changes in risk factors are likely to reflect genetic-environmental interactions and may have important implications for understanding CHD risk. The present study examines the heritability of changes in CHD risk factors, using data from the two examinations by the Kaiser Permanente Women Twins Study, performed a decade apart. The sample consisted of 348 pairs of women twins who participated in both examinations, including 203 MZ pairs and 145 DZ pairs. Average ages at the two examinations were 41 and 51 years, respectively. By means of three different statistical analytic approaches, moderate heritability estimates were demonstrated for changes in LDL cholesterol (h2 = .25-.36) and in HDL cholesterol (h2 = .23-.58), some of which were statistically significant. Although small to moderate heritability estimates were found for systolic blood pressure (.18-.37; P < .05 for some estimates), no genetic influence on changes in diastolic blood pressure was detected. Based on longitudinal twin data in women, this study demonstrates a genetic influence on changes in both lipoprotein risk factors and systolic blood pressure over a decade. In addition to environmental factors, which clearly are operating, the effect of various "variability genes" may be acting independently of the genetic influences on the absolute levels of these risk factors. Both mapping the gene(s) underlying intraindividual variations in these CHD risk factors and understanding their function(s) could lead to targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.

Adult↗
PubMed1997

Effectiveness of two strategies for dissemination of sun-protection policy in New South Wales primary and secondary schools.

With rising rates of skin cancer in Australia, there is a need to examine strategies to reduce sun exposure among children. This study aimed to determine the effectiveness of a multifaceted dissemination strategy compared with a simple mail-out strategy in promoting the adoption of comprehensive SunSmart skin protection policies and practices in primary and secondary schools in New South Wales. It also aimed to examine characteristics of the primary and secondary schools that adopted a comprehensive SunSmart policy before and after the intervention. Four hundred randomly selected primary schools and all 381 high schools in New South Wales were randomised to one of two intervention groups. Pretest and post-test surveys of principals were undertaken in 1991 and 1992. Intervention 1 was a simple mail-out of a sample sun-protection policy kit. Intervention 2 comprised the mail-out of the policy kit and a follow-up mail-out of a staff development module. There was a strong intervention effect on adoption of a comprehensive sun-protection policy in primary schools (21 per cent for the 'mail' group compared with 44 per cent for 'mail and staff support' group) but not in high schools (6 per cent and 11 per cent). There was little relationship between adoption of a comprehensive sun-protection policy and sun-protection practices in primary or secondary schools. Further research is needed to determine the most effective ways of ensuring that adoption of a comprehensive sun-protection policy results in effective implementation of sun-protection practices in schools.

Adolescent↗
PubMed1997

The identification of children with developmental coordination disorder by class and physical education teachers.

BACKGROUND: Children diagnosed with developmental coordination disorder (DCD) have difficulty performing coordinated movements. In addition, these children have been found to have long-term social, emotional, behavioural and academic problems. Early identification is therefore important, and teachers may be very useful in this identification process. AIMS: In the present study, the ability of physical education and class teachers to identify children with coordination problems using the Movement Assessment Battery for Children checklist was assessed. SAMPLES: A total of 171 children was initially assessed. From this sample, 32 children found to have coordination problems were compared with 32 control children, matched on age, sex and Verbal IQ. METHODS: Motor coordination difficulty was identified in children aged between 9 and 11 years using the performance test of the Movement Assessment Battery for Children (MABC; Henderson & Sugden, 1992). These scores were then compared with the scores on the MABC checklist which was given to the child's class and physical education teachers. RESULTS: Class teachers were only able to identify 25 per cent of the children with DCD, whereas physical education teachers were able to identify 49 per cent of the DCD children. CONCLUSION: These differences were discussed in relation to the contextual settings in which the children were tested, based on the theory described by Sugden & Sugden (1991) in the development of their Motor Competence Checklist (MCC).

Analysis of Variance↗
PubMed1997

SP-A enhances uptake of bacillus Calmette-Guérin by macrophages through a specific SP-A receptor.

Surfactant-associated protein A (SP-A) is a C-type lectin that is involved in surfactant metabolism as well as host defense functions in the lung. We have recently identified a receptor on macrophages [specific 210-kDa SP-A receptor (SPR210)] that binds SP-A. In the current study we have investigated the role of SP-A in mediating uptake of bacillus Calmette-Guérin (BCG) by rat macrophages and human monocytes and have examined the role of the macrophage SPR210 in this process. 125I-labeled SP-A bound BCG in a Ca(2+)-, carbohydrate-, and dose-dependent manner. To examine association of SP-A-BCG complexes with macrophages, BCG were opsonized with SP-A and were incubated with rat bone marrow-derived macrophages (RBMM), rat alveolar macrophages (RAM), or human monocytes at a 1-to-1 ratio for 4 h. The cells were washed, fixed in formalin, and stained with auramine-rhodamine. Cell-associated organisms were enumerated by fluorescent microscopy. The percentage of cells with one or more associated BCG was increased by SP-A from 27% of RBMM with BCG alone to 54% with SP-A-BCG complexes; 1-16% in RAM; and 39-67% in human monocytes. This enhanced uptake was dependent on the dose of SP-A, with maximal increases seen with 10 micrograms/ml. Electron microscopic analysis supported the conclusion that organisms were ingested by and not simply bound to the macrophages. Inclusion of SPR210 antibodies blocked association of SP-A-BCG complexes, suggesting a role for SPR210 in mediating the interaction of SP-A-BCG with the macrophages. This was further supported by the finding that modulation of SPR210 activity resulted in altered SP-A-BCG uptake. These results demonstrate that SP-A binds to BCG and that uptake of these SP-A-BCG complexes is mediated in part by the SPR210 on rat macrophages and human monocytes.

Animals↗