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Biomedical subjects

P Green

Publications and source records attributed to P Green.

At least 37 records · Page 2Linked to original sources

Enhanced free radical scavenging and decreased lipid peroxidation in the rat fetal brain after treatment with ethyl docosahexaenoate.

In order to explore possible mechanisms to explain previously observed decreases in fetal brain lipid peroxidation (LPO) following intraamniotic administration of ethyl docosahexaenoate (Et-DHA) to near term fetuses, the hydroxyl radical trapping capacity of Et-DHA treated fetal brain preparations was compared to control ethyl oleate injected fetuses by electron spin resonance using 5,5'-dimethyl-1-pyrroline N-oxide (DMPO) probe. Lipid extracts from control brains showed little hydroxyl radical scavenging activity, whereas those from the Et-DHA injected animals exhibited an almost 70% decrease in the amount of DMPO-OH adducts. A marked decrease (58%) in LPO formation was noticed in the Et-DHA treated animals compared to controls. The Et-DHA treatment related trapping capacity resided in the phospholipid fraction of the lipid extract, which was enriched in both docosahexaenoic acid and aminophospholipid contents. The decreased LPO production, as well as increased production of prostaglandin E(2) and nitric oxide by the fetal brain following Et-DHA administration, could be mimicked by a synthetic quinone possessing both hydroxyl radical producing and LPO propagation inhibiting properties. The data are consistent with the possibility that the neuroprotective effect of Et-DHA might be due to possible free radical scavenging ability of the brain tissue and interference with LPO propagation.

Amnion↗

PCR cloning of type II polyhydroxyalkanoate biosynthesis genes from two Pseudomonas strains.

Two polyhydroxyalkanoate synthase genes, phaC1 from Pseudomonas pseudoalcaligenes HBQ06 and phaC2 from Pseudomonas nitroreducens 0802, were cloned using a PCR cloning strategy based on the type II pha loci property of Pseudomonas strains. The complete open reading frames (ORFs) of phaC1 (P. nitroreducens HBQ06) and phaC2 (P. nitroreducens 0802) were identified from the PCR products. Using the sequence information, the complete PHA synthase genes were PCR cloned directly from the genomic DNA and expressed in Escherichia coli as confirmed by Fourier transform-infrared spectroscopy and gas chromatography. The differences between PhaC1 and PhaC2 were analyzed and the two proteins were suggested to contain different functions and evolution history.

Acyltransferases↗

Ethyl docosahexaenoate-associated decrease in fetal brain lipid peroxide production is mediated by activation of prostanoid and nitric oxide pathways.

Previously we have shown that intraamniotic administration of ethyl docosahexaenoate (Et-DHA) to pregnant rats resulted in decreased lipid peroxidation in the fetal brain, under a variety of conditions (S. Glozman, P. Green, E. Yavin, J. Neurochem. 70 (1998) 2482-2491). In the present study we examine the potential mechanisms to explain this effect. This was done by a pharmacological approach, utilizing brain slice preparations from Et-DHA treated or control rats in the presence of various agents and examining the formation of products in the tissue slices or incubation medium. Et-DHA treated brains produced 2-3-fold more prostanoids (PN) than control brains, indicating cyclooxygenase (COX) activation. Indomethacin at 50 microM inhibited PN formation and also abolished Et-DHA induced decrease in lipid peroxides, as evident by the levels of thiobarbituric acid reactive substances (TBARS) released in the medium. The phospholipase A2 inhibitors quinacrine and p-bromophenacyl bromide added at 0.1 mM concentration each to either slices from controls or Et-DHA treated fetal brains, decreased TBARS production. Et-DHA treated brains released 2.2-fold more nitric oxide (NO) than control brains and NO synthase (NOS) inhibitors abolished this effect. Increasing the concentration of NO by the addition of an NO donor greatly decreased the concentration of the TBARS in the medium. These results suggest that at least some of the effect of Et-DHA on decreased lipid peroxidation may be explained by a shift of oxygen species utilization via enzymatically regulated, therefore metabolically controlled, COX and NOS activities.

Animals↗

Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis.

OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n = 13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor tenosynovectomy. Synovial membrane cells were dissociated from connective tissue by enzyme digestion and cultured in vitro for 48 hours, and harvested supernatants were assayed for the cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by enzyme-linked immunosorbent assay. Gelatin zymography was performed to demonstrate enzyme activity. Statistical analysis was performed using Student's paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009) and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3 were similar in all synovial sample groups. Zymography demonstrated enzyme activity in all synovium samples from all 9 patients assessed. CONCLUSION: Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are important in the tissue degradation seen in RA. Increased production of the enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible explanation for the worse prognosis and increased rupture rate associated with invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that angiogenesis may have a role in tenosynovial proliferation and invasion of tendons.

Adult↗

Base rates of WAIS-R VIQ-PIQ differences in 1593 psychiatric inpatients.

The purpose of this study was to provide the psychologist with base-rate tables for the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Verbal IQ-Performance IQ difference scores in 1593 psychiatric inpatients. Subtables also were provided for each of three primary psychiatric diagnoses (schizophrenia spectrum disorders, bipolar disorders, and depression). The base rates of VIQ-PIQ splits in the full inpatient sample, and those for the subsamples based on primary psychiatric diagnosis, were very similar to those reported in the WAIS-R standardization sample. Consistent with past research on the standardization sample, the VIQ-PIQ split was correlated positively with Full Scale IQ (FSIQ), indicating that larger splits are more common at the higher IQ levels. Therefore, base-rate tables also were provided for the total inpatient sample split into five IQ groupings.

Adult↗

Symptom expectation after minor head injury. A comparative study between Canada and Lithuania.

OBJECTIVES: The purpose of the present study is to compare the frequency and nature of expected symptoms in Lithuania (a country where the chronic post-concussive syndrome is largely unknown) with that in Canada. METHODS: A symptom checklist was administered to two subject groups selected from local companies in Kaunas, Lithuania, and Edmonton, Canada, respectively. Subjects were asked to imagine having suffered head trauma with loss of consciousness in a motor vehicle accident, and to check off symptoms they expected might arise from the injury. For symptoms they anticipated, they were asked to select the period of time they expected those symptoms to persist. RESULTS: In both the Lithuanian and Edmontonian groups, the pattern of symptoms anticipated closely resembled the acute symptoms commonly reported by accident victims with minor head injury. Yet, while many Edmontonians also anticipated symptoms to last months or years, very few Lithuanian subjects selected any symptoms as being likely to persist in a chronic manner. CONCLUSIONS: In Lithuania, despite the frequent experience of minor head injury in motor vehicle accidents, there is a very low rate of expectation of any chronic sequelae from such an injury, contrasting greatly with the response shown in Canada, where the prevalence of the chronic post-concussive syndrome is higher. Symptom expectation in some countries may be an important factor in the development of the chronic post-concussive syndrome.

Brain Injury, Chronic↗

Validation of the computerized assessment of response bias in litigating patients with head injuries.

The detection of malingering in neuropsychological assessment requires valid measures of incomplete effort. The Computerized Assessment of Response Bias (CARB) is a digit-recognition procedure designed to detect poor effort during a neuropsychological evaluation. We examined the CARB performance of a consecutive series of litigating patients (N = 119) with a full range of head-injury severity, from trivial to severe. Patients with trivial or mild head injuries performed more poorly than did patients with frank brain injuries. Specifically, patients with moderate to severe traumatic brain injuries obtained higher total scores and demonstrated briefer response latencies than did patients with trivial or mild head injuries.

Adult↗

Effort has a greater effect on test scores than severe brain injury in compensation claimants.

Nine-hundred and four consecutive patients, including 80 neurological patients and 470 with head injuries, were given neuropsychological tests. All 43 test scores were converted to normative Z-scores and averaged, giving an Overall Test Battery Mean (OTBM). A variable measuring effort correlated 0.73 with the OTBM. The OTBM mean score was 1.20 SD lower in those who failed the Word Memory Test (WMT) than in those who passed the WMT. Sub-optimal effort suppressed the OTBM 4.5 times more than did moderate-severe brain injury. When only those making a good effort were included, patients with severe brain injuries and neurological diseases scored significantly lower than groups presumed to have no neurological impairment, but these group differences were not seen when all cases were analysed together. These data illustrate the importance of measuring and controlling for sub-optimal effort in individual neuropsychological evaluations, as well as in empirical research with similar groups of patients.

Adult↗

Automated finishing with autofinish.

Currently, the genome sequencing community is producing shotgun sequence data at a very high rate, but finishing (collecting additional directed sequence data to close gaps and improve the quality of the data) is not matching that rate. One reason for the difference is that shotgun sequencing is highly automated but finishing is not: Most finishing decisions, such as which directed reads to obtain and which specialized sequencing techniques to use, are made by people. If finishing rates are to increase to match shotgun sequencing rates, most finishing decisions also must be automated. The Autofinish computer program (which is part of the computer software package) does this by automatically choosing finishing reads. Autofinish is able to suggest most finishing reads required for completion of each sequencing project, greatly reducing the amount of human attention needed. sometimes completely finishes the project, with no human decisions required. It cannot solve the most complex problems, so we recommend that Autofinish be allowed to suggest reads for the first three rounds of finishing, and if the project still is not finished completely, a human finisher complete the work. We compared this Autofinish-Hybrid method of finishing against a human finisher in five different projects with a variety of shotgun depths by finishing each project twice--once with each method. This comparison shows that the Autofinish-Hybrid method saves many hours over a human finisher alone, while using roughly the same number and type of reads and closing gaps at roughly the same rate. Autofinish currently is in production use at several large sequencing centers. It is designed to be adaptable to the finishing strategy of the lab--it can finish using some or all of the following: resequencing reads, reverses, custom primer walks on either subclone templates or whole clone templates, PCR, or minilibraries. Autofinish has been used for finishing cDNA, genomic clones, and whole bacterial genomes (see http://www.phrap.org).

Contig Mapping↗

Docosahexaenoic acid sources for the developing brain during intrauterine life.

Docosahexaenoic acid (DHA, 22: 6n-3) and arachidonic acid (AA, 20: 4n-6) provision to the developing fetus, with emphasis towards brain and vascular system growth, is a subject of increasing concern particularly under pathological conditions associated with premature birth or in utero growth restriction following obstruction of the maternal-fetal blood flow. Most of DHA, but also AA accretion under physiological conditions, is maternally dependent and requires adequate maternal nutrition and normally functioning placental-fetal circulation. It has been demonstrated that unlike other fatty acids (FA), DHA is preferentially transported across the placenta into the fetal circulation. The selective transplacental DHA transfer is probably mediated by specific carrier proteins. While some of the latter may be acting in fetal organs, the mechanism(s) for the selective accumulation of DHA in brain is still unknown. The fetal brain and also the fetal liver are capable of producing DHA from linolenic (LnA, 18:3 n-3) acid. How effective this local elongation-desaturation mechanism for DHA provision is and to what degree this route is activated in premature births is not clear. Transfer of DHA via the fetal gastrointestinal tract is an additional route to provide DHA to other fetal organs. As indicated by animal model studies, it holds the potential for DHA supply when the maternal pathway is compromised.

Animals↗

Measuring improvement or decline on the WAIS-R in inpatient psychiatry.

Psychologists in inpatient psychiatric settings sometimes are asked to assess whether patients improve or decline in intellectual functioning. The impetus for this referral question may be a perceived change in psychiatric status, an acute neuropathological event, e.g., a head injury, or a suspicion of an early dementing process. For this study, data from 100 inpatients who completed the WAIS-R on two separate admissions were used to calculate confidence bands for measurement error surrounding test-retest difference scores. The analysis indicated that, if the retest interval is three months or less, significant practice effects must be factored into the interpretation of difference scores. A table for the interpretation of difference scores at different testing intervals is provided

Adolescent↗

Effort testing in patients with fibromyalgia and disability incentives.

OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of cognitive dysfunction using 2 new validated instruments in patients with fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests designed to detect exaggerated memory complaints as part of a battery of psychological tests and self-report questionnaires. RESULTS: A large percentage of patients with FM who were on or seeking disability benefits failed the effort tests. Only 2 patients with FM who were working and/or not claiming disability benefits and no patient with RA scored below the cutoffs for exaggeration of memory difficulties. CONCLUSION: This study illustrates the importance of assessing for exaggeration of cognitive symptoms and biased responding in patients with FM presenting for disability related evaluations.

Adult↗

Why clinicians often disagree about the validity of test results.

Examining the validity of test results using specialised methods is still a relatively new venture and many different approaches are taken to the same task. This paper discusses some of the reasons why discrepant results and differing conclusions may be arrived at by clinicians or researchers, depending on their theoretical and practical choices. These choices include whether to test for effort, what methods to use, how to employ effort tests, what failure criteria to apply and how to interpret individual results. Equally important is the decision about whether or not to employ effort testing to remove error from data in group research studies. No concensus has yet been reached on the need for systematic effort testing in group studies but there are indications that it should be a serious consideration because controlling for invalid data can lead to altered conclusions.

Attitude of Health Personnel↗

Effects of injury severity and cognitive exaggeration on olfactory deficits in head injury compensation claims.

The purpose of this study was to examine the relationship between exaggeration and scores on a test of olfactory discrimination in patients being assessed in connection with a claim for financial benefits. Participants were 448 patients referred to a private practice in Edmonton, Alberta, Canada for psychological or neuropsychological assessment, related to evaluation of impairment and disability resulting from a work-related or non-work related accident. All patients were involved in some form of compensation claim at the time of their evaluation. All patients completed two tests designed to detect exaggerated cognitive deficits, the Computerized Assessment of Response Bias (CARB) and the Word Memory Test (WMT) as part of their evaluation. The diagnostic groups included 322 head injury cases, varying from very minor to very severe. Normative data for the smell test were derived from 126 patients with orthopedic injuries who passed both the CARB and the WMT. Patients with more severe traumatic brain injuries were 10-12 times more likely to have olfactory deficits than persons with trivial to mild head injuries. In a subgroup of patients who failed either the CARB or the WMT, there was no relationship between injury severity and total scores on the smell test. Therefore, the dose-response relationship between brain injury severity and olfactory deficits is severely attenuated when patients who are probably exaggerating their cognitive deficits are included in the analyses. Those patients with trivial to mild head injuries who demonstrated adequate effort on both the CARB and the WMT were no more likely to show olfactory deficits than the non-head-injured orthopedic control subjects. Therefore, anosmia following mild traumatic brain injury should not be concluded from self-reports or from tests of smell unless tests of effort have been passed. Effort should also be controlled in group studies of olfaction.

Adult↗

Inactivation of p53 by HTLV type 1 and HTLV type 2 Tax trans-activators.

Human T cell lymphotropic virus type II (HTLV-2) was originally isolated from a patient with a hairy T cell leukemia. It has been associated with rare cases of CD8(+) T lymphoproliferative disorders, and has a controversial role as a pathogen. The loss of p53 function, as a consequence of mutation or inactivation, increases the chances of genetic damage. Indeed, the importance of p53 as a tumor suppressor is evident from the fact that over 60% of all human cancers have a mutant or inactive p53. p53 status has been extensively studied in HTLV-1-infected cell lines. Interestingly, despite the fact that p53 mutations have been found in only a minority of cells, the p53 functions were found to be impaired. We have analyzed the functional activity of the p53 tumor suppressor in cells transformed with HTLV-2 subtypes A and B. As with HTLV-1-infected cells, abundant levels of the p53 protein are detected in HTLV-2 virus-infected cell lines. Using p53 reporter plasmid or induction of p53-responsive genes in response to gamma-irradiation, the p53 was found to be transcriptionally inhibited in HTLV-2-infected cells. Interestingly, although Tax-2A and-2B inactivate p53, the Tax-2A protein appears to inhibit p53 function less efficiently than either Tax-1 or Tax-2B in T cells, but not in fibroblasts.

Animals↗