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Biomedical subjects

J Cooper

Publications and source records attributed to J Cooper.

At least 91 records · Page 5Linked to original sources

Crystal structure of cardosin A, a glycosylated and Arg-Gly-Asp-containing aspartic proteinase from the flowers of Cynara cardunculus L.

Aspartic proteinases (AP) have been widely studied within the living world, but so far no plant AP have been structurally characterized. The refined cardosin A crystallographic structure includes two molecules, built up by two glycosylated peptide chains (31 and 15 kDa each). The fold of cardosin A is typical within the AP family. The glycosyl content is described by 19 sugar rings attached to Asn-67 and Asn-257. They are localized on the molecular surface away from the conserved active site and show a new glycan of the plant complex type. A hydrogen bond between Gln-126 and Manbeta4 renders the monosaccharide oxygen O-2 sterically inaccessible to accept a xylosyl residue, therefore explaining the new type of the identified plant glycan. The Arg-Gly-Asp sequence, which has been shown to be involved in recognition of a putative cardosin A receptor, was found in a loop between two beta-strands on the molecular surface opposite the active site cleft. Based on the crystal structure, a possible mechanism whereby cardosin A might be orientated at the cell surface of the style to interact with its putative receptor from pollen is proposed. The biological implications of these findings are also discussed.

Amino Acid Sequence↗

Predictors of time loss after back injury in nurses.

STUDY DESIGN: A 2-year prospective inception cohort study of back injury in nurses. OBJECTIVES: To determine the extent to which characteristics of nurses, of the injury, and of the workplace predict occurrence and duration of time loss from work after back injury. SUMMARY OF BACKGROUND DATA: During 2 years, 320 nurses incurred 416 back injuries at a large teaching hospital in Winnipeg, Canada. Nurses injured on preselected wards were targeted for early intervention, including provision of modified work, whereas nurses injured on other wards received the usual care. METHODS: Time loss attributable to the back injury during the 6 months after injury was analyzed. Three statistical models were used to examine occurrence of time loss (logistic regression), duration of time loss (Tobit regression), and duration of time loss once an injury incurring time loss had been documented (least-squares regression). RESULTS: In 218 of the 416 injuries, the injured nurse consented to interview. Whereas perceived disability was related to whether a time loss injury would ensue, self-reported pain was strongly related to the duration of time loss once an injury had become a time loss injury. Duration of time loss was reduced by participation in the return-to-work program. Mechanism of injury, specifically injury occurring while lifting patients, resulted in greater time loss. CONCLUSIONS: Focusing on reducing the perception of disability at the time of injury is critical to preventing time loss, but once time loss has occurred, offer of modified work and attention to pain reduction are warranted. The findings add to the evidence that workplace-based intervention programs can be effective in reducing the morbidity resulting from back injury.

Accidents, Occupational↗

Irradiation with or without misonidazole for patients with stages IIIB and IVA carcinoma of the cervix: final results of RTOG 80-05. Radiation Therapy Oncology Group.

PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.

Adult↗

Human platelets exclusively bind oxidized low density lipoprotein showing no specificity for acetylated low density lipoprotein.

The widely studied macrophage scavenger receptor system is known to bind both acetylated low density lipoprotein and oxidized low density lipoprotein. Although only the latter ligand has been shown to occur in vivo, acetylated low density lipoprotein is often used to evaluate the contribution of scavenger receptors to different (patho)physiologic processes, assuming that all existing subtypes of scavenger receptors recognise both lipoproteins. In the present work, we identify human platelets as the first natural cell type to bind oxidized low density lipoprotein without showing specificity for acetylated low density lipoprotein. Consequently, platelets possess exclusive receptor(s) for oxidized low density lipoprotein distinct from the 'classical' scavenger receptor AI/AII. From the data presented in this work, we conclude that the class B scavenger receptor CD36 (GPIV) is responsible for this exclusive oxidized low density lipoprotein binding.

Animals↗

Three-dimensional imaging by deconvolution microscopy.

Deconvolution is a computational method used to reduce out-of-focus fluorescence in three-dimensional (3D) microscope images. It can be applied in principle to any type of microscope image but has most often been used to improve images from conventional fluorescence microscopes. Compared to other forms of 3D light microscopy, like confocal microscopy, the advantage of deconvolution microscopy is that it can be accomplished at very low light levels, thus enabling multiple focal-plane imaging of light-sensitive living specimens over long time periods. Here we discuss the principles of deconvolution microscopy, describe different computational approaches for deconvolution, and discuss interpretation of deconvolved images with a particular emphasis on what artifacts may arise.

Artifacts↗

Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization.

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues, so abnormalities outside the brain might be expected. Although involvement of nuclei and mitochondria in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains; mitochondria are organelles that regulates apoptotic cell death. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.

Adolescent↗

Present and future possibilities for defining a phenotype for specific language impairment.

This brief report summarizes a workshop that was held at the National Institutes of Health in April 1998. The goal of the workshop was to further the development of a definition for the phenotype of specific language impairment (SLI). The report includes a discussion of research recommendations that will refine our current views of the definition of the SLI phenotype and sets out priority areas that are in need of further study to help advance understanding of this complex language-based disorder.

Forecasting↗

Ethical issues and their practical application in a psychological autopsy study of suicide.

The psychological autopsy research method provides detailed information about a suicide using various sources including, coroners' reports, medical records and information gathered from interviews with key informants. The purpose of this article is to discuss the ethical issues that arose when undertaking a psychological autopsy study in Manchester, UK. The sensitive nature of the research is discussed, in particular in relation to the participation of the close relatives and friends of the deceased. These issues, identified from the experiences of other researchers in this field and by conducting a study in Manchester, had implications for the research design and its application. The reactions of the informants who took part in the Manchester study are reported, and their comments should be used to refine future studies on sensitive topics. Their suggestions on their needs and the needs of the suicidal have implications for future health service provision.

Attitude to Health↗

Nortestosterone is not a naturally occurring compound in male cattle.

Nortestosterone (beta-NT) is a hormonal growth promoter banned from livestock production in the EU. Following injection, the major metabolite in cattle is the 17 alpha-epimer (alpha-NT). However, this also occurs naturally in pregnant cattle. It is not known whether alpha-NT is also endogenous to intact or castrated male cattle. Three surveys were undertaken to assess whether alpha-NT is naturally produced in this subset of the population. Bile samples from a total of 1,281 cattle (73 bulls and 1,208 steers) from 366 herds were collected at slaughter and initially screened by using a semi-automated EIA with multi-analyte immunoaffinity chromatography (IAC) clean-up. Bile samples from a further 38 male cattle (10 bulls and 28 steers) were analysed by high-resolution gas chromatography-mass spectrometry (GC-MS) with IAC pretreatment. Only samples containing more than 2 ng/ml alpha-NT were subjected to GC-MS. With 2 ng/ml alpha-NT as a threshold for confirmatory testing, the false positive rate of the screening EIA was 1.8%. Bulls (n = 16) and steers (n = 179) from government farms (n = 2) and which were not treated with exogenous beta-NT, did not have measurable concentrations of alpha-NT in their bile. Bulls (n = 35) and steers (n = 606) taken from herds (n = 204) which had no previous history of illegal growth promoter abuse also did not have alpha-NT in their bile. Of 32 bulls and 451 steers of unknown treatment history sampled from herds (n = 160), 56 steers from 19 herds contained GC-MS confirmed concentrations of alpha-NT higher than the limit of quantification of the assay LOQ (0.7 ng/ml). Of these animals, two had beta-NT-containing injection sites and five had residues of the beta-agonists clenbuterol and mabuterol. Examination of the animal movement and ownership histories of the 56 confirmed positive animals strongly suggested that exogenous beta-NT had been administered at the presenting farm. It is concluded that alpha-NT is not endogenous to this subset of the cattle population and that detection of this hormone in bile from bulls and steers constitutes evidence of abuse.

Anabolic Agents↗

Placental transfer of fentanyl in early human pregnancy and its detection in fetal brain.

We have investigated the transfer of fentanyl across the early human placenta in 38 women (8-14 weeks' gestation) undergoing termination of pregnancy. After administration of a bolus dose of fentanyl 2 micrograms kg-1 at induction of anaesthesia, maternal blood n = 38), placenta (n = 38), amniotic fluid (n = 38) and fetal brain (n = 7) samples were collected and assayed for fentanyl by radioimmunoassay. Fentanyl was detected in all placental and fetal brain samples but not in amniotic fluid. There was a rapid decrease in fentanyl concentrations in maternal serum after the bolus but placental concentrations had not started to decline 30 min later. There was no difference in placental drug concentrations at different gestational ages. These data suggest that there is rapid transfer of fentanyl to the fetus in early pregnancy and that the drug remains in fetal tissue for some time after the initial dose is given to the mother.

Abortion, Therapeutic↗

Randomized trial of informed consent and recruitment for clinical trials in the immediate preoperative period.

BACKGROUND: The standard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials, partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment. Alternative randomization methods have been advocated that may address these and other concerns. METHODS: After institutional ethics committee gave its approval, the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial. Patients were allocated randomly to one of five methods of randomization and consent: one-sided informed consent (the most common approach), prerandomized consent to experimental treatment, prerandomized consent to standard treatment, one-sided physician-modified informed consent, or one-sided patient-modified informed consent. Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified. RESULTS: The randomization method did not result in any significant difference in recruitment rates: one-sided informed consent, 55.6%; prerandomized consent to experimental treatment, 53.3%; prerandomized consent to standard treatment, 53%; one-sided physician-modified informed consent, 60.7%; and one-sided patient-modified informed consent, 56.7% (P = 0.66). Multivariate predictors of recruitment were patient age >45 yr (odds ratio, 1.44; 95% confidence interval [CI], 1.08 to 1.93), English-speaking at home (1.49; 1.0 to 2.21), and male researcher-male patient interaction (1.37; 1.20 to 1.57). CONCLUSIONS: No evidence emerged that alternative randomization and consent designs resulted in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery. Older, male patients were more likely to provide consent.

Adolescent↗

The clinical efficacy of paremyd with and without dapiprazole in subjects with light and dark brown irides.

BACKGROUND: Paremyd, a mydriatic formulation of 0.25% tropicamide and 1.0% hydroxyamphetamine hydrobromide provides adequate dilation for binocular indirect ophthalmoscopy in young Caucasians. We studied the clinical effectiveness of Paremyd in dilating heavily pigmented eyes by comparing its mydriatic efficacy in Blacks, Asians and Caucasians with light and dark brown irides. We also evaluated the efficacy of one drop of dapiprazole (Rev-Eyes) in reversing Paremyd-induced mydriasis in our subject sample. METHODS: In a masked, randomized, controlled experimental design, several visual functions which included pupillary dilation, near visual acuity, amplitude of accommodation, ocular hyperemia, and discomfort glare were measured at 30-min intervals, for a total of 300 min, in subjects dilated with a single drop of Paremyd in each eye. Ease of binocular indirect ophthalmoscopy was also assessed. A 3-way analysis of variance was used to assess changes in these measures as function of irides color/pigmentation (designated as light or dark brown iris color), presence or absence of dapiprazole, and test time interval. RESULTS: We found that subjects in our light brown irides group (mainly Caucasians) dilated faster than subjects in our dark brown irides group (mainly Blacks). Dapiprazole increased the speed of recovery from pupillary dilation for all subjects, but more so for those with light rather than dark brown irides. Similarly, subjects with light rather than dark brown irides recovered accommodative function more quickly. Although neither the use of dapiprazole nor the degree of iris color/pigmentation was significantly related to visual acuity or glare discomfort, there was a clear trend that these visual measures were affected to a greater degree in subjects with dark brown (primarily Blacks) rather than light brown irides. Overall, Paremyd provided adequate dilation for binocular indirect ophthalmoscopy in all subjects irrespective of iris color/pigmentation. CONCLUSIONS: Our data indicate that a single drop of Paremyd provides adequate mydriasis, without significant side effects, for routine fundus examination of all subjects, independent of iris color/pigmentation. Furthermore, a single drop of dapiprazole was effective in speeding the return of pupillary dilation in most subjects, but had no significant effect on accommodation, near visual acuity or glare discomfort. Side effects such as stinging upon instillation, conjunctival hyperemia, and a few instances of ptosis, with possible additional cost to patients, appear to lessen its overall clinical benefit.

Accommodation, Ocular↗

Registration of stereo and temporal images of the retina.

The registration of retinal images is required to facilitate the study of the optic nerve head and the retina. The method we propose combines the use of mutual information as the similarity measure and simulated annealing as the search technique. It is robust toward large transformations between the images and significant changes in light intensity. By using a pyramid sampling approach combined with simulated reannealing we find that registration can be achieved to predetermined precision, subject to choice of interpolation and the constraint of time. The algorithm was tested on 49 pairs of stereo images and 48 pairs of temporal images with success.

Algorithms↗

Is suicide risk taken seriously in heavy drinkers who harm themselves?

OBJECTIVE: The aim of the study was to examine whether a known history of heavy drinking adversely influences the assessment and management of deliberate self-harm (DSH) by accident and emergency department staff. METHOD: Standard assessment forms on a consecutive series of 909 DSH cases were examined. Estimated suicide risk and clinical management were compared in patients who reported high (more than 7 units per day) and low/moderate alcohol intake. RESULTS: Heavy drinkers had higher rates of several risk factors for suicide. They were more likely to be judged as at high risk of suicide and further self-harm, and were more likely to receive clinical management appropriate to people at high risk. However, a logistic regression analysis revealed that it was not alcohol use itself but risk factors that were more common in heavy drinkers that predicted clinical management. CONCLUSION: The results suggest that heavy drinkers are in general judged to be at higher risk of suicide and managed accordingly. However, training for accident and emergency department staff should emphasize the importance of alcohol as an independent risk factor for suicide.

Adult↗

Psychological autopsy study of suicides by people aged under 35.

BACKGROUND: In the past two decades the suicide rate in young people has risen in the UK and other countries. AIMS: To identify the characteristics of people aged under 35 who commit suicide. METHOD: Psychological autopsy study with case-control design. Cases were 84 suicides and probable suicides (open verdicts). Controls were 64 age- and gender-matched non-suicides obtained through the general practices of the matched cases. MAIN VARIABLES: social, including employment status, marital status and living circumstances; life events and interpersonal difficulties; clinical, including current psychiatric disorder, alcohol and drug misuse, previous self-harm and personality disorder. RESULTS: A large number of highly significant social, interpersonal and clinical differences between suicides and controls was found. Factor analysis identified two groups of variables within each of the social, interpersonal and clinical domains which were independently linked to suicide, corresponding to: acute, severe mental disorder and chronic disorder of behaviour; rootlessness and social withdrawal; chronic and recent interpersonal problems. CONCLUSIONS: A broad prevention strategy is needed to reverse the recent rise in the suicide rate in young people.

Adolescent↗

Relationship between static and dynamic foot postures in professional baseball players.

STUDY DESIGN: Observational study of static and dynamic foot postures in professional baseball players. BACKGROUND: Throughout the course of a professional baseball season, running, cutting, and sprinting activities can produce a breakdown in players' foot function, causing overuse injuries. OBJECTIVES: To investigate the relationship between static and dynamic foot postures; to determine the occurrence of abnormal foot postures in professional baseball players and the incidence of overuse injuries in the lower extremity; and to compare the foot postures of pitchers to those of positional players. METHODS AND MEASURES: The foot postures of 74 professional baseball players were evaluated at rest and during gait. Measures of static foot posture were obtained with a goniometer and included the subtalar neutral position, forefoot/rearfoot position, ankle joint dorsiflexion, tibial angle in standing, and calcaneal angle in standing. The FootTrak motion analysis system provided measures of dynamic foot posture (rearfoot supination and pronation) during the stance phase of gait. A questionnaire was completed by players who reported previous lower extremity injuries. The chi-square statistic was used to determine the associations between forefoot position (varus or valgus) and the amount of foot pronation during gait. RESULTS: The forefoot varus and calcaneal valgus in standing was significantly associated with the maximum pronation during the stance phase of gait. Of the 65 players who demonstrated excessive pronation (> 8 degrees), 28 (43%) also reported a previous lower extremity injury. No statistically significant difference occurred, however, between injured and uninjured players with respect to the mean values of static or dynamic foot posture. In addition, foot postures were not associated with a player's position. CONCLUSIONS: Selected measures of static rearfoot and forefoot postures may have value in predicting dynamic rearfoot movement during the stance phase of gait. Excessive pronation in the baseball players we studied was not found to be a significant contributing factor in the development of overuse injuries.

Baseball↗