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Biomedical subjects

P Green

Publications and source records attributed to P Green.

At least 55 records · Page 3Linked to original sources

Global water resources: vulnerability from climate change and population growth.

The future adequacy of freshwater resources is difficult to assess, owing to a complex and rapidly changing geography of water supply and use. Numerical experiments combining climate model outputs, water budgets, and socioeconomic information along digitized river networks demonstrate that (i) a large proportion of the world's population is currently experiencing water stress and (ii) rising water demands greatly outweigh greenhouse warming in defining the state of global water systems to 2025. Consideration of direct human impacts on global water supply remains a poorly articulated but potentially important facet of the larger global change question.

Agriculture↗

The role of fractalkine in the recruitment of monocytes to the endothelium.

Recombinant fractalkine possesses both chemoattractive and adhesive properties in vitro. Previous studies have demonstrated an upregulation of this molecule on the membranes of activated human endothelial cells and hypothesised that fractalkine plays a role in the recruitment and adherence of monocytes to the activated endothelium. Here we present data analysing both the adhesive and chemoattractive properties of this chemokine expressed by activated human umbilical vein endothelial cells. We demonstrate that both recombinant fractalkine and endogenously produced fractalkine function as adhesion molecules, tethering monocytes to the endothelium. However, our data demonstrate that although recombinant fractalkine has the potential to function as a potent monocyte chemoattractant, the endogenous fractalkine cleaved from activated human umbilical vein endothelial cells is not responsible for the observed chemotaxis in this model. Instead, we show that monocyte chemoattractant protein-1 (MCP-1), secreted from the activated human umbilical vein endothelial cells, is responsible for the chemotaxis of these monocytes.

Blotting, Western↗

Analysis of expressed sequence tags indicates 35,000 human genes.

The number of protein-coding genes in an organism provides a useful first measure of its molecular complexity. Single-celled prokaryotes and eukaryotes typically have a few thousand genes; for example, Escherichia coli has 4,300 and Saccharomyces cerevisiae has 6,000. Evolution of multicellularity appears to have been accompanied by a several-fold increase in gene number, the invertebrates Caenorhabditis elegans and Drosophila melanogaster having 19,000 and 13,600 genes, respectively. Here we estimate the number of human genes by comparing a set of human expressed sequence tag (EST) contigs with human chromosome 22 and with a non-redundant set of mRNA sequences. The two comparisons give mutually consistent estimates of approximately 35,000 genes, substantially lower than most previous estimates. Evolution of the increased physiological complexity of vertebrates may therefore have depended more on the combinatorial diversification of regulatory networks or alternative splicing than on a substantial increase in gene number.

Alternative Splicing↗

California Verbal Learning Test indicators of suboptimal performance in a sample of head-injury litigants.

Cutoff scores suggested by Millis, Putnam, Adams, and Ricker (1995) for detecting suboptimal performance on indices from the California Verbal Learning Test (CVLT) were evaluated using data from 193 compensation-seeking participants. All participants claimed to have suffered a blow to the head in an accident causing subsequent deterioration in cognitive function. The participants were divided into those with negligible or possible mild brain injuries and those with clear evidence of moderate to severe brain injuries. In addition to the CVLT, all participants were administered the Computerized Assessment of Response Bias (CARB), a two-alternative forced choice test of recognition memory that is used to detect feigned cognitive impairment. For all CVLT indices, the distributions of outcome (valid vs. suboptimal performance) was unrelated to age and brain injury severity, and only weakly associated with education. However, a significantly higher proportion of males than females obtained scores in the suboptimal performance range. The CVLT indices were not fully redundant with each other with respect to binary participant classifications; substantial disagreement between pairwise classifications was found among those participants who obtained at least one score in the suboptimal performance range. CVLT index classifications were also found to be non-redundant with classifications based on CARB scores. The CVLT may thus add useful data over and above that obtained from symptom validity testing. However, the data suggest that the use of the strategy where any one or more below-cutoff CVLT scores are considered a positive indicator of suboptimal performance may be associated with a higher than acceptable false-positive error rate.

Adolescent↗

Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function.

We have analyzed the functional activity of the p53 tumor suppressor in human T-cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant levels of the p53 protein were detected in both HTLV-2A and -2B virus-infected cell lines. The p53 was functionally inactive, however, both in transient-transfection assays using a p53 reporter plasmid and in induction of p53-responsive genes in response to gamma irradiation. We further investigated HTLV-2A Tax and HTLV-2B Tax effects on p53 activity. 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 transient-cotransfection assays, Tax-1 and Tax-2B inactivated p53 by 80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-2A does not increase the steady-state level of cellular p53 as well as Tax-1 or -2B does in the same assays. Cotransfection assays demonstrated that Tax-2A could efficiently transactivate CREB-responsive promoters to the same level as Tax-1 and Tax-2B, indicating that the protein was functional. This report provides evidence of the first functional difference between the HTLV-2A and -2B subtypes. This comparison of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will provide important insights into the mechanism of HTLV transformation.

Cell Line, Transformed↗

Predictive validity of WAIS-R VIQ-PIQ splits in persons with major depression.

We selected a sample of patients with depression (N = 70) and used Bayesian analyses to examine the diagnostic predictive validity of the Wechsler Adult Intelligence Scale-Revised Verbal IQ (VIQ) minus Performance IQ (PIQ) difference score for depression. The patients showed average VIQ-PIQ differences in the expected direction (i.e., VIQ > PIQ). However, based on sensitivity, specificity, and positive predictive value statistics, we concluded that the VIQ-PIQ split has very low predictive validity in persons with depression.

Adult↗

Monooxygenases play only a minor role in resistance to synthetic pyrethroids in the cattle tick, Boophilus microplus.

We investigated the role of monooxygenases in resistance to synthetic pyrethroids (SPs) in the cattle tick, Boophilus microplus. We found that monooxygenases play only a minor role in resistance to SPs in both resistant and susceptible strains of B. microplus. We blocked the monooxygenases with piperonyl butoxide (PBO) and simultaneously applied the SPs, flumethrin and cypermethrin to larval B. microplus. PBO increased the effect of flumethrin (synergism ratios 2.7-8.9) more than it increased the effect of cypermethrin (synergism ratios 1.9-3.1). Of the four strains tested, Parkhurst, which is resistant to SPs, was the least affected by the addition of PBO (synergism ratios after cypermethrin was applied 1.9; after flumethrin 2.7) whereas N.R.F.S., the strain susceptible to SPs, was the most affected by synergism between PBO and SPs (synergism ratio after cypermethrin was applied 3.1; after flumethrin 8.9). We hypothesize that B. microplus lacks monooxygenases capable of conferring resistance to SPs because it and its recent ancestors were blood-feeders rather than herbivores.

Animals↗

Detecting resistance to organophosphates and carbamates in the cattle tick Boophilus microplus, with a propoxur-based biochemical test.

Rapid and sensitive detection of resistance to insecticides in arthropods is needed. In the cattle tick. Boophilus microplus, resistance to a variety of acaricides is widespread. The most commonly used assay for resistance, the larval packet test, takes at least two, but generally six weeks for a one-host tick like B. microplus to complete and may take up to three months to complete for three-host ticks. Here we describe a test for resistance to organophosphate acaricides that can be used on larvae and adult ticks which takes less than 24 hours. The test measures the difference in acetylcholinesterase (AChE) activity in homogenates of ticks in the presence and absence of propoxur, a carbamate acaricide. We found clear discrimination of organophosphate-susceptible and organophosphate-resistant adults with 100 microM propoxur. AChE from susceptible ticks had almost no activity at this concentration of propoxur whereas AChE from resistant ticks had 67% of its potential activity. AChE from heterozygote ticks could also be distinguished from AChE from homozygous-susceptible and homozygous-resistant ticks. This is the first biochemical test for resistance to an acaricide. Rapid, sensitive tests like ours will allow resistance to organophosphates to be detected soon after it develops in the field, thus, the spread of resistance might be slowed and the useful life of acaricides extended.

Acetylcholinesterase↗

Detecting malingering in head injury litigation with the Word Memory Test.

The Word Memory Test (WMT) is a relatively new computer-based test that is designed to measure both verbal memory and biased responding (i.e. malingering). The purpose of this study was to examine the performance of a large sample of patients involved in head injury litigation on the WMT measures of biased responding. The patients were divided into two groups, those with relatively mild head injuries (n = 234) and those with moderate or severe brain injuries (n = 64). The patients with less severe injuries performed significantly poorer on the WMT measures of biased responding.

Adult↗

Identification of candidate coding region single nucleotide polymorphisms in 165 human genes using assembled expressed sequence tags.

Using assembled expressed sequence tags (ESTs) from 50 different cDNA libraries, we have identified contigs that represent the complete coding sequences of 850 known human genes, and have scanned these for high quality sequence substitutions. We report the identification and characteristics of 201 candidate single nucleotide polymorphisms found in the coding sequences (cSNPs) of 165 of these genes. Using a conservative calculation, coding region nucleotide diversity (the average number of differences between any pair of chromosomes) was found to be 3 per 10,000 bp based on this data. This analysis reveals that assembled ESTs from multiple libraries may provide a rich source of comparative sequences to search for cSNPs in the human genome.

Amino Acid Substitution↗

Developmental changes in rat brain membrane lipids and fatty acids. The preferential prenatal accumulation of docosahexaenoic acid.

Information on the prenatal accumulation of rat brain membrane lipids is scarce. In this study we investigated in detail the fatty acid (FA) composition of the rat brain, on each day from embryonic day 12 (E12) up to birth, and on 8 time points during the first 16 days of postnatal life, and correlated the FA changes with well-described events of neurogenesis and synaptogenesis. Between E14 and E17, there was a steep increase in the concentration of all the FAs: 16:0 increased by 136%, 18:0 by 139%, 18:1 by 92%, 20:4n-6 by 98%, 22:4n-6 by 116%, 22:5n-6 by 220%, and 22:6n-3 by 98%. After this period and up to birth, the concentration of the FAs plateaued, except that of 22:6n-3, which accumulated further, reaching an additional increase of 75%. After birth, except 22:5n-6, all FAs steadily increased at various rates. Estimation of the FA/PL molar ratios showed that prenatally the ratios of all the FAs either decreased or remained constant, but that of 22:6n-3 increased more than 2-fold; postnatally the ratios remained constant, with the exception of 22:4n-6 and 22:5n-6, which decreased. In conclusion, prenatal accumulation of brain fatty acids parallels important events in neurogenesis. 22:6n-3 is exceptional inasmuch in its steep accumulation occurs just prior to synaptogenesis.

Animals↗

Relationship between degenerative joint disease and hip joint laxity by use of distraction index and Norberg angle measurement in a group of cats.

OBJECTIVE: To determine the relationship between degenerative joint disease (DJD) and passive laxity of the hip joint in a group of cats. DESIGN: Prospective study. ANIMALS: A select (nonrandomized) group of 78 cats. PROCEDURE: Standard hip-extended radiographic views and compression and distraction views of the pelvis were obtained from cats during sedation. Radiographs were evaluated, using an Orthopedic Foundation for Animals (OFA)-like scoring system for dogs. Passive joint laxity was measured, using Norberg angle (NA) and distraction index (DI). Hip laxity in cats with DJD was compared with hip laxity in cats without DJD. RESULTS: Hip dysplasia (HD) was subjectively diagnosed radiographically in 25 of 78 (32%) cats using the OFA-like scoring system. Nineteen cats had mild HD 4 had moderate HD, and 2 had severe HD. Fifteen of the 25 cats with HD had DJD. The NA ranged from 56 to 105. The mean NA in cats with DJD was (84 degrees) significantly lower than in cats without DJD (95 degrees). The DI ranged from 0.2 to 0.84. The mean DI for cats with DJD was (0.6) significantly higher than that for cats without DJD (0.49). Cats with a DI < 0.4 did not have DJD. Cats had an increased likelihood of having DJD with increased laxity in the coxofemoral joint, as measured by NA or DI. CLINICAL IMPLICATIONS: The mean NA for radiographically normal cats (92.4 degrees) was lower than that in radiographically normal dogs (103 degrees). The overall mean DI for cats in this group (0.51) is similar to dogs of breeds with high joint laxity, such as the Labrador Retriever (0.5). As in dogs, there is a relationship between DJD and laxity in the hip joint of cats.

Animals↗

IL-4-induced eosinophil accumulation in rat skin is dependent on endogenous TNF-alpha and alpha 4 integrin/VCAM-1 adhesion pathways.

IL-4 has been implicated in the pathogenesis of a number of allergic inflammatory disease states where the accumulation of eosinophils is a prominent feature. The aim of the present study was to use an isotopic in vivo model to investigate the ability of recombinant rat IL-4 in inducing eosinophil accumulation in rat skin. 111In-eosinophil accumulation in response to intradermally injected IL-4 was measured during 0 to 4 h, 24 to 28 h, and 48 to 52 h. Accumulation was detected during the first two periods, but not at the later time point. The accumulation during 24 to 28 h, which was dose dependent, was investigated in detail. Administration i.v. of an anti-rat VCAM-1 mAb, but not an anti-rat ICAM-1 mAb, inhibited the accumulation of 111In-eosinophils induced by IL-4 (maximum inhibition, 80%). Further, when the 111In-eosinophils were pretreated in vitro with an anti-beta 2 integrin mAb, an anti-alpha 4 integrin mAb, or a combination of both mAbs, before their injection into recipient rats, the IL-4-induced cell accumulation was inhibited by 63, 60, and 74%, respectively. Finally, coadministration of IL-4 with the soluble TNF receptor (p55)-IgG fusion protein significantly reduced the 111In-eosinophil accumulation induced by the cytokine, and TNF-alpha was detected in IL-4-injected skin sites by both immunostaining and bioassay. Our results demonstrate that IL-4 is a potent inducer of eosinophil accumulation in vivo, the response being dependent on the endogenous generation of TNF-alpha, beta 2 integrins, and alpha 4 integrin/VCAM-1 interactions.

Animals↗

Mechanisms of docosahexaenoic acid accretion in the fetal brain.

Docosahexaenoic acid (DHA, 22:6 n-3) is the major polyunsaturated fatty acid (PUFA) in the adult mammalian brain. DHA is an essential fatty acid (FA) since it, or its short chain precursor, alpha-linolenic acid (LnA, 18:3 n-3), have to be obtained in the diet. Moreover, dietary n-3 FA deficiency is associated with biochemical changes in the brain and with disturbances in vision and other neurological parameters. Under normal nutritional conditions, fetal brain DHA accumulation is substantial, with a "DHA accretion spurt" being demonstrated in the last period of gestation. This accumulation is supported by the maternal supply of DHA or LnA, but selectivity of DHA accumulation is probably a placental function whose mechanism is lately being clarified. The fetal gastrointestinal (G-I) tract may be instrumental in supplying DHA to the fetal brain under certain conditions, such as following intra-amniotic administration of ethyl-docosahexaenoate (Et-DHA). In this pathway, DHA is supplied independently of the maternal metabolism, and the fetal liver is apparently involved. The fetal G-I tract may be advantageous for DHA supply in cases of maternal-placental insufficiency resulting in intrauterine growth retardation. The fetal brain itself is capable of metabolizing LnA to DHA, without the participation of the fetal liver, thus contributing to the accumulation of its own DHA during one of the most crucial periods of its development.

Animals↗

Assessing intellectual functioning in persons with schizophrenia spectrum disorders using a seven subtest short form of the WAIS-R.

The purpose of this study was to examine the concurrent validity of a Wechsler Adult Intelligence Scale-Revised (WAIS-R) seven subtest short form. Researchers have shown that the IQ scores estimated by this short form correlate highly with full-form IQ scores in several patient populations. We compared the full WAIS-R scores with the seven subtest short form estimated IQs in a sample of patients with psychotic disorders (n = 190). The VIQs, PIQs, and FSIQs estimated by the short form were highly correlated with the full form IQs (rs ranging from 0.95 to 0.98). Similar to previous research, the mean difference scores were small (ranging from one point to virtually no difference). In general, the seven subtest short from has adequate concurrent validity and is suitable for assessing intellectual functioning in persons with psychotic disorders.

Adult↗

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Adolescent↗