title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
Antiepileptic drug use and rates of hip bone loss in older men: a prospective study. | To test the hypotheses that older community dwelling men taking non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of hip bone loss. We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n = 4060), NEIAED user (use of NEIAED only at either examination, n = 100), or EIAED user (use of EIAED only at either examination, n = 62). After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was -0.35%/year among nonusers compared with -0.53%/year among NEIAED users (p = 0.04) and -0.46%/year among EIAED users (p = 0.31). Multivariable adjusted rate of loss was -0.60%/year among men taking NEIAED at both examinations, -0.51%/year among men taking NEIAED at one examination only, and -0.35%/year among nonusers (p for trend = 0.03). Findings were similar at hip subregions. Use of non-enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men. | 18,765,648 |
Dual activation of phospholipase C-epsilon by Rho and Ras GTPases. | Phospholipase C-epsilon (PLC-epsilon) is a highly elaborated PLC required for a diverse set of signaling pathways. Here we use a combination of cellular assays and studies with purified proteins to show that activated RhoA and Ras isoforms directly engage distinct regions of PLC-epsilon to stimulate its phospholipase activity. Purified PLC-epsilon was activated in a guanine nucleotide- and concentration-dependent fashion by purified lipidated K-Ras reconstituted in PtdIns(4,5)P(2)-containing phospholipid vesicles. Whereas mutation of two critical lysine residues within the second Ras-association domain of PLC-epsilon prevented K-Ras-dependent activation of the purified enzyme, guanine nucleotide-dependent activation by RhoA was retained. Deletion of a loop unique to PLC-epsilon eliminated its activation by RhoA but not H-Ras. In contrast, removal of the autoinhibitory X/Y-linker region of the catalytic core of PLC-epsilon markedly activates the enzyme (Hicks, S. N., Jezyk, M. R., Gershburg, S., Seifert, J. P., Harden, T. K., and Sondek, J. (2008) Mol. Cell, 31, 383-394), but PLC-epsilon lacking this regulatory region retained activation by both Rho and Ras GTPases. Additive activation of PLC-epsilon by RhoA and K- or H-Ras was observed in intact cell studies, and this additivity was recapitulated in experiments in which activation of purified PLC-epsilon was quantified with PtdIns(4,5)P(2)-containing phospholipid vesicles reconstituted with purified, isoprenylated GTPases. A maximally effective concentration of activated RhoA also increased the sensitivity of purified PLC-epsilon to activation by K-Ras. These results indicate that PLC-epsilon can be directly and concomitantly activated by both RhoA and individual Ras GTPases resulting in diverse upstream control of signaling cascades downstream of PLC-epsilon. | 18,765,661 |
The sushi domains of secreted GABA(B1) isoforms selectively impair GABA(B) heteroreceptor function. | GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. GABA(B) receptors are promising drug targets for a wide spectrum of psychiatric and neurological disorders. Receptor subtypes exhibit no pharmacological differences and are based on the subunit isoforms GABA(B1a) and GABA(B1b). GABA(B1a) differs from GABA(B1b) in its ectodomain by the presence of a pair of conserved protein binding motifs, the sushi domains (SDs). Previous work showed that selectively GABA(B1a) contributes to heteroreceptors at glutamatergic terminals, whereas both GABA(B1a) and GABA(B1b) contribute to autoreceptors at GABAergic terminals or to postsynaptic receptors. Here, we describe GABA(B1j), a secreted GABA(B1) isoform comprising the two SDs. We show that the two SDs, when expressed as a soluble protein, bind to neuronal membranes with low nanomolar affinity. Soluble SD protein, when added at nanomolar concentrations to dissociated hippocampal neurons or to acute hippocampal slices, impairs the inhibitory effect of GABA(B) heteroreceptors on evoked and spontaneous glutamate release. In contrast, soluble SD protein neither impairs the activity of GABA(B) autoreceptors nor impairs the activity of postsynaptic GABA(B) receptors. We propose that soluble SD protein scavenges an extracellular binding partner that retains GABA(B1a)-containing heteroreceptors in proximity of the presynaptic release machinery. Soluble GABA(B1) isoforms like GABA(B1j) may therefore act as dominant-negative inhibitors of heteroreceptors and control the level of GABA(B)-mediated inhibition at glutamatergic terminals. Of importance for drug discovery, our data also demonstrate that it is possible to selectively impair GABA(B) heteroreceptors by targeting their SDs. | 18,765,663 |
Novel variants of Oct-3/4 gene expressed in mouse somatic cells. | It has been suggested that Oct-3/4 may regulate self-renewal in somatic stem cells, as it does in embryonic stem cells. However, recent reports raise the possibility that detection of human Oct-3/4 expression by RT-PCR is prone to artifacts generated by pseudogene transcripts and argue against a role for Oct-3/4 in somatic cells. In this study, we clarified Oct-3/4 expression in mouse somatic tissues using designed PCR primers, which can exclude amplification of its pseudogenes. We found that novel alternative transcripts are indeed expressed in somatic tissues, rather than the normal length transcripts in germline and ES cells. The alternative transcripts indicate the expression of two kinds of truncated proteins. Furthermore, we determined novel promoter regions that are sufficient for the expression of Oct-3/4 transcript variants in somatic cells. These findings provide new insights into the postnatal role of Oct-3/4 in somatic tissues. | 18,765,667 |
Tibial fixation of bone-patellar tendon-bone grafts in anterior cruciate ligament reconstruction: a cadaveric study of bovine bone screw and biodegradable interference screw. | The use of interference screw fixation for bone-patellar tendon-bone grafts in anterior cruciate ligament fixation is well established. No previous study has compared bovine bone screws and biodegradable interference screws or demonstrated their efficacy for requirements associated with early rehabilitation. There is no difference in tension loss and pull-out strength between bovine bone screws and biodegradable interference screws. Controlled laboratory study. Anterior cruciate ligament reconstructions with bone-patellar tendon-bone allografts were performed in 40 human tibiae from 20 donors. A bovine bone screw and a polylevolactide interference screw were used for tibial fixation in each pair. A cyclic testing protocol with varying magnitude and orientation of the graft loading was developed. Cyclic tests were performed at 1 Hz for 5000 cycles with a peak force of 200 N applied to the graft. Survival rate and postcyclic-test pull-out strength were compared. Fifteen of 20 reconstructions fixed with bovine bone screws and 17 of 20 fixed with biodegradable screws reached 5000 cycles. Graft tension drop after the 5000 cycles averaged 19.7 N ( +/- 12.9) for bovine bone screws and 18.9 N ( +/- 16.3) for biodegradable screws. There were no significant differences in tension loss and pull-out strength between the 2 types of screws. Bovine bone screws are comparable to biodegradable interference screws in providing stable tibial fixation in anterior cruciate ligament reconstruction using bone-patellar tendon-bone allografts. The use of bovine bone screws may be comparable to the popular biodegradable interference screws used for anterior cruciate ligament reconstruction in postsurgery rehabilitation. | 18,765,676 |
Use of labeled oral minimal model to measure hepatic insulin sensitivity. | The ability to accurately quantify indexes of the individual role of glucose (GE(L)) and insulin (S(I)(L)) in the suppression of endogenous glucose production (EGP) would improve the understanding of liver metabolism. Measuring these indexes during an IVGTT by minimal modeling of tracer labeled and unlabeled glucose data is often unreliable, possibly due to an inadequate description of EGP included in the Minimal Model. Moreover, a validation of the assumptions of the Minimal Model on EGP data has never been done. Recently, Krudys et al. (Krudys KM, Dodds MG, Nissen SM, Vicini P. Am J Physiol Endocrinol Metab 288: E1038-E1046, 2005) have proposed a PK/PD (pharmacokinetic/pharmacodynamic) model of the EGP profile that occurs during an intravenous glucose tolerance test (IVGTT); however, this model has also not been validated. The aim of this study was thus to test the Minimal Model, the PK/PD model, and six alternative EGP descriptions on recent model-independent EGP data of 20 subjects obtained with a triple-tracer meal protocol. Model performance was compared in terms of data fit, precision of the estimated parameters, and physiological plausibility. Neither the PK/PD nor the traditional Minimal Model were able to accurately describe EGP data or provide reliable estimates of the indexes. In contrast, one of the new models performed best by showing a good fit and providing accurate and precise estimates of hepatic sensitivity indexes: GE(L) = 0.013 +/- 0.001 dl x kg(-1) x min(-1); S(I)(L) = 5.34 +/- 0.47 10(-4) dl x kg(-1) x min(-1) per microU/ml (42 and 34%, respectively, of total sensitivity indexes GE(TOT) and S(I)(TOT)). Although this model requires further validation, it has the potential to improve our understanding of the role of the liver in pathophysiological states. | 18,765,681 |
Vaccination of mice with a Yop translocon complex elicits antibodies that are protective against infection with F1- Yersinia pestis. | Yersinia pestis, the bacterial agent of plague, secretes several proteins important for pathogenesis or host protection. The F1 protein forms a capsule on the bacterial cell surface and is a well-characterized protective antigen but is not essential for virulence. A type III secretion system that is essential for virulence exports Yop proteins, which function as antiphagocytic or anti-inflammatory factors. Yop effectors (e.g., YopE) are delivered across the host cell plasma membrane by a translocon, composed of YopB and YopD. Complexes of YopB, YopD, and YopE (BDE) secreted by Yersinia pseudotuberculosis were purified by affinity chromatography and used as immunogens to determine if antibodies to the translocon could provide protection against Y. pestis in mice. Mice vaccinated with BDE generated high-titer immunoglobulin G antibodies specific for BDE, as shown by enzyme-linked immunosorbent assay and immunoblotting, and were protected against lethal intravenous challenge with F1(-) but not F1(+) Y. pestis. Mice passively immunized with anti-BDE serum were protected from lethal challenge with F1(-) Y. pestis. The YopB protein or a complex of YopB and YopD (BD) was purified and determined by vaccination to be immunogenic in mice. Mice actively vaccinated with BD or passively vaccinated with anti-BD serum were protected against lethal challenge with F1(-) Y. pestis. These results indicate that anti-translocon antibodies can be used as immunotherapy to treat infections by F1(-) Y. pestis. | 18,765,742 |
Community-based inquiry improves critical thinking in general education biology. | National stakeholders are becoming increasingly concerned about the inability of college graduates to think critically. Research shows that, while both faculty and students deem critical thinking essential, only a small fraction of graduates can demonstrate the thinking skills necessary for academic and professional success. Many faculty are considering nontraditional teaching methods that incorporate undergraduate research because they more closely align with the process of doing investigative science. This study compared a research-focused teaching method called community-based inquiry (CBI) with traditional lecture/laboratory in general education biology to discover which method would elicit greater gains in critical thinking. Results showed significant critical-thinking gains in the CBI group but decreases in a traditional group and a mixed CBI/traditional group. Prior critical-thinking skill, instructor, and ethnicity also significantly influenced critical-thinking gains, with nearly all ethnicities in the CBI group outperforming peers in both the mixed and traditional groups. Females, who showed decreased critical thinking in traditional courses relative to males, outperformed their male counterparts in CBI courses. Through the results of this study, it is hoped that faculty who value both research and critical thinking will consider using the CBI method. | 18,765,755 |
Evaluation of intra-annual variation in U.S. Geological Survey National Water Quality Assessment ground water quality data. | Assessment of ground-water quality trends under the U.S. Geological Survey National Water-Quality Assessment Program (NAWQA) included the analysis of samples collected on a quarterly basis for 1 yr between 2001 and 2005. The purpose of this quarterly sampling was to test the hypothesis that variations in the concentration of water-quality parameters of selected individual wells could demonstrate that the intra-annual variation was greater or less than the decadal changes observed for a trend network. Evaluation of more than 100 wells over this period indicates that 1 yr of quarterly sampling is not adequate to address the issue of intra-annual variation because variations seem to be random and highly variable between different wells in the same networks and among networks located in different geographical areas of the USA. In addition, the data from only 1 yr makes it impossible to assess whether variations are due to univariate changes caused by land use changes, hydrologic variations due to variable recharge, or variations caused by ground-water pumping. These data indicate that funds allocated to this activity can be directed to the collection of more effective trend data, including age dating of all wells in the NAWQA network using multiple techniques. Continued evaluation of data and updating of monitoring plans of the NAWQA program is important for maintaining relevance to national goals and scientific objectives. | 18,765,766 |
Short-term sustainability of drainage water reuse: spatio-temporal impacts on soil chemical properties. | Greater urban demand for finite water resources, increased frequency of drought resulting from erratic weather, and increased pressure to reduce drainage water volumes have intensified the need to reuse drainage water. A study was initiated in 1999 on a 32.4-ha saline-sodic field (Lethent clay loam series; fine, montmorillonitic, thermic, Typic Natrargid) located on the west side of California's San Joaquin Valley (WSJV) with the objective of evaluating the sustainability of drainage water reuse with respect to impact on soil quality. An evaluation after 5 yr of irrigation with drainage water is presented. Geo-referenced measurements of apparent soil electrical conductivity (EC(a)) were used to direct soil sampling at 40 sites to characterize the spatial variability of soil properties (i.e., salinity, Se, Na, B, and Mo) crucial to the soil's intended use of growing Bermuda grass (Cynodon dactylon (l.) Pers.) for livestock consumption. Soil samples were taken at 0.3-m increments to a depth of 1.2 m at each site in August 1999, April 2002, and November 2004. Drainage water varying in salinity (0.8-16.2 dS m(-1)), SAR (5.4-52.4), Mo (80-400 microg L(-1)), and Se (<1-700 microg L(-1)) was applied to the field since July 2000. An analysis of the general temporal trend shows that overall soil quality has improved due to leaching of B from the top 0.6 m of soil; salinity and Na from the top 1.2 m, but primarily from 0 to 0.6 m; and Mo from the top 1.2 m. Short-term sustainability of drainage water reuse is supported by the results. | 18,765,781 |
The RNA-binding protein XSeb4R: a positive regulator of VegT mRNA stability and translation that is required for germ layer formation in Xenopus. | VegT represents a localized maternal determinant essentially required for endoderm formation in Xenopus. Here, we report on the identification of the RNA-binding protein XSeb4R as a positive regulator of VegT. XSeb4R interacts directly with the 3'-untranslated region of VegT mRNA, stabilizes it, and stimulates translation. Ablation of XSeb4R activity results in impairment of endoderm and mesoderm formation, while ectopic expression of XSeb4R in ectodermal cells induces endodermal and mesodermal gene expression. These observations unravel a novel mode of VegT regulation at the post-transcriptional level that is essential for germ layer formation in Xenopus. | 18,765,788 |
Rice jmjC domain-containing gene JMJ706 encodes H3K9 demethylase required for floral organ development. | Histone lysine methylation is an important epigenetic modification with both activating and repressive roles in gene expression. Jumonji C (jmjC) domain-containing proteins have been shown to reverse histone methylation in nonplant model systems. Here, we show that plant Jumonji C proteins have both conserved and specific features compared with mammalian homologues. In particular, the rice JMJD2 family jmjC gene JMJ706 is shown to encode a heterochromatin-enriched protein. The JMJ706 protein specifically reverses di- and trimethylations of lysine 9 of histone H3 (H3K9) in vitro. Loss-of-function mutations of the gene lead to increased di- and trimethylations of H3K9 and affect the spikelet development, including altered floral morphology and organ number. Gene expression and histone modification analysis indicates that JMJ706 regulates a subset of flower development regulatory genes. Taken together, our data suggest that rice JMJ706 encodes a heterochromatin-associated H3K9 demethylase involved in the regulation of flower development in rice. | 18,765,808 |
Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. | Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors. | 18,765,809 |
MEDME: an experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment. | DNA methylation is an important component of epigenetic modifications that influences the transcriptional machinery and is aberrant in many human diseases. Several methods have been developed to map DNA methylation for either limited regions or genome-wide. In particular, antibodies specific for methylated CpG have been successfully applied in genome-wide studies. However, despite the relevance of the obtained results, the interpretation of antibody enrichment is not trivial. Of greatest importance, the coupling of antibody-enriched methylated fragments with microarrays generates DNA methylation estimates that are not linearly related to the true methylation level. Here, we present an experimental and analytical methodology, MEDME (modeling experimental data with MeDIP enrichment), to obtain enhanced estimates that better describe the true values of DNA methylation level throughout the genome. We propose an experimental scenario for evaluating the true relationship in a high-throughput setting and a model-based analysis to predict the absolute and relative DNA methylation levels. We successfully applied this model to evaluate DNA methylation status of normal human melanocytes compared to a melanoma cell strain. Despite the low resolution typical of methods based on immunoprecipitation, we show that model-derived estimates of DNA methylation provide relatively high correlation with measured absolute and relative levels, as validated by bisulfite genomic DNA sequencing. Importantly, the model-derived DNA methylation estimates simplify the interpretation of the results both at single-loci and at chromosome-wide levels. | 18,765,822 |
Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. | We have studied the potential contribution of ABCG2 (breast cancer resistance protein) to resistance to nucleoside analogues. In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. With Transwell studies in MDCK cells and transport experiments with vesicles from Sf9 and HEK293 cells, we show that ABCG2 is able to transport not only the nucleotide CdAMP, like several other ATP-binding cassette transporters of the ABCC (multidrug resistance protein) family, but also the nucleoside cladribine itself. Expression of ABCG2 in cells results in a substantial decrease of intracellular CdATP, explaining the resistance against cladribine. The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors. | 18,765,824 |
Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans. | To gain a better understanding of the genetic variants associated with carboplatin-induced cytotoxicity in individuals of African descent, we present a step-wise approach integrating genotypes, gene expression, and sensitivity of HapMap cell lines to carboplatin. Cell lines derived from 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to carboplatin-induced cytotoxicity. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of carboplatin for 72 h. Gene expression of 89 HapMap YRI cell lines was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. Single nucleotide polymorphism genotype and the percent survival at different treatment concentrations along with carboplatin IC50 were linked through whole genome association. A second association test was done between single nucleotide polymorphism genotype and gene expression, and linear regression was then used to capture those genes whose expression correlated to drug sensitivity phenotypes. This approach allows us to identify genetic variants that significantly associate with sensitivity to the cytotoxic effects of carboplatin through their effect on gene expression. We found a gene (GPC5) whose expression is important in all carboplatin treatment concentrations as well as many genes unique to either low (e.g., MAPK1) or high (e.g., BRAF, MYC, and BCL2L1) concentrations of drug. Our whole genome approach enables us to evaluate the contribution of genetic and gene expression variation to a wide range of cellular phenotypes. The identification of concentration specific genetic signatures allows for potential integration of pharmacokinetics, pharmacodynamics, and pharmacogenetics in tailoring chemotherapy. | 18,765,826 |
Alternative wnt signaling is initiated by distinct receptors. | An unanswered question in the field of signal transduction research is how different signaling pathways are activated with strict specificity in a temporally and spatially controlled manner. Because extracellular ligands and membrane receptors constitute the first signaling modalities for most pathways, selectivity in ligand-receptor binding likely dictates the outcome of downstream signaling events. Unfortunately, possible complexities underlying ligand-receptor interactions are often overlooked. Here, we discuss basic principles of signal transduction initiated at the cell membrane, with the Wnt pathway, which harbors a multitude of ligands and receptors, as an example. | 18,765,832 |
Comparison of production traits between pigs with and without the Escherichia coli F4 receptors in a White Duroc x Erhualian intercross F2 population. | To evaluate the influence of enterotoxigenic Escherichia coli (ETEC) F4 receptors on production traits in pigs, ETEC F4ab, F4ac, and F4ad adhesion phenotypes and 27 traits related to growth, carcass, meat quality, and length of the small intestine in a White Duroc x Erhualian intercross population were measured. Performance data revealed that pigs with the F4ab or F4ac receptor (adhesive phenotypes) had greater (P < 0.01) ADG during the fattening period (from 46 to 240 d) and carcass weight and length at 240 d than pigs lacking the receptors (nonadhesive phenotype). Conversely, animals having the F4ad receptor had less (P < 0.01) ADG during the fattening period and carcass weight than those lacking the receptor. In total, 8 adhesion patterns (A to H) for the 3 F4 strains were observed in this experimental population. Pigs with both F4ab and F4ac receptors (phenotype B) had greater (P < 0.01) ADG, carcass weight, and length at 240 d compared with pigs without the F4 receptors. No difference was found (P > 0.05) in traits related to meat quality, fatness, and length of the small intestine between pigs with or without the receptors. On the basis of the antagonistic relationship between susceptibility to F4ab/ac and production traits, we speculate that the prevalence of the ETEC F4ab/ac adhesive phenotype in pig populations is attributable to balanced natural and artificial selection. | 18,765,849 |
Space requirements of weaned pigs during a sixty-minute transport in summer. | Currently, there are no trucking quality assurance recommendations for space allowance of weaned pigs during transport in the United States. The objective of this research was to establish a first estimate of the space requirements of weaned pigs during transport in summer based on measures of animal well-being. A commercial semi-trailer was fitted with compartments that provided 0.05, 0.06, and 0.07 m(2)/pig, which were replicated on the upper and lower deck, with a constant 100 pigs per compartment. Cameras were placed in each experimental compartment to record behaviors and postures of pigs during transport. The frequencies of standing, lying, sitting, standing/rearing on another pig, and lying/huddling on top of another pig were recorded using 1-min scan samples during the entire duration of transport. Blood samples were collected and BW and lesion scores recorded from 32 pigs per space allowance for physiological and immune measures before and after transport (n = 32 pigs/treatment). Pigs were transported for 60 +/- 5 min to the wean-to-finishing site using the same route for each replicate during summer (temperature: 28.4 +/- 1.2 degrees C and relative humidity: 59.8 +/- 4.4% within the trailer). Data were analyzed using the MIXED procedure (SAS Institute Inc., Cary, NC). Cortisol, hematocrit, blood urea nitrogen, total protein, albumin, aspartate aminotransferase, creatine kinase, and gamma-glutamyl transferase increased (P < 0.05) after transport regardless of space allowance. Plasma glucose and BW decreased (P < 0.05) after transport regardless of space allowance. Lesion scores increased (P < 0.001) after transport and were greater (P < 0.05) for barrows compared with gilts. The neutrophil to lymphocyte ratio was greater (P < 0.005) for pigs transported at 0.05 m(2)/pig compared with pigs transported at 0.06 and 0.07 m(2)/pig. Pigs transported at 0.05 m(2)/pig lay down less (P < 0.05) than pigs transported at 0.06 and 0.07 m(2)/pig between 30 and 60 min of transport. Greater neutrophil to lymphocyte ratio and less lying behavior performed by pigs transported at 0.05 m(2)/pig suggest that a minimum space allowance of 0.06 m(2)/pig was preferable when transporting weaned pigs for 60 min during summer in this study. | 18,765,850 |
Effect of Scutellaria flavonoids on KCN-induced damages in rat pheochromocytoma PC12 cells. | Cerebral hypoxia is known to be involved in many neurodegenerative diseases such as Alzheimer's and cerebrovascular dementia. The present study was designed to investigate the effects of flavonoids from aerial part of Scutellaria baicalensis Georgi (SSF) on potassium cyanide (KCN) -induced hypoxic cytotoxicity in rat pheochromocytoma cell line PC12, and to understand the probable mechanism. The rat pheochromocytoma cell line PC12 was subjected to hypoxia by 200 microM KCN for 30 min. The cytotoxicity of KCN was assessed by cell viability assay, morphological observation, lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production, and the activities of superoxide dismutase (SOD) and Na+-K+-ATPase measurements. The effects of SSF on the changes induced by KCN in PC12 cells were detected. Treatment of PC12 cells with 200 micriM KCN for 30 min increased cell death when compared with control, as assayed by MTT reduction, morphological observation and lactate dehydrogenase release measurement. These cell lesions were accompanied by disorders in SOD and Na+-K+-ATPase activities as well as MDA production. In contrast, the PC12 cells pre-treated with SSF for 24 h prior to 200 microM KCN exposure have shown protection against hypoxic toxicity. The KCN - induced decreased cell viability and activities of SOD and Na+-K+-ATPase, as well as increased MDA production were reversed by SSF pre-treatment. SSF exerted neuroprotections against KCN - induced hypoxic cytotoxicity in PC12 cells and the probable mechanisms involved free radicals and energy metabolism. Our findings may have implications in future in the treatment of neurodegenerative diseases. | 18,765,882 |
A method for 3D electron density imaging using single scattered x-rays with application to mammographic screening. | Screening mammography is the current standard in detecting breast cancer. However, its fundamental disadvantage is that it projects a 3D object into a 2D image. Small lesions are difficult to detect when superimposed over layers of normal, heterogeneous tissue. In this work, we examine the potential of single scattered photon electron density imaging in a mammographic environment. Simulating a low-energy (<20 keV) scanning pencil beam, we have developed an algorithm capable of producing 3D electron density images from a single projection. We have tested the algorithm by imaging parts of a simulated mammographic accreditation phantom containing lesions of various sizes. The results indicate that the group of imaged lesions differ significantly from background breast tissue (p<0.005), confirming that electron density imaging may be a useful diagnostic test for the presence of breast cancer. | 18,765,886 |
A preliminary study for non-invasive quantification of manganese in human hand bones. | Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12+/-0.68 microg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16-0.78 microg Mn/g Ca and mean value of 0.63+/-0.30 microg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population. | 18,765,892 |
The three-dimensional cultivation of the carcinoma cell line HepG2 in a perfused chip system leads to a more differentiated phenotype of the cells compared to monolayer culture. | We describe a polymer chip with a grid-like architecture that it is intended for the three-dimensional cultivation of cells with an active nutrient and gas supply. The chip is typically made from polymethyl methacrylate or polycarbonate but can also be manufactured from biodegradable polymers, such as poly(lactic-co-glycolic acid). Different designs of the chip can be realized. In this study, we evaluated a chip with 506 microcontainers of the size of 300 x 300 x 300 microm that are capable of housing up to 6 million cells, and its suitability as a tissue-specific culture system for the carcinoma cell line HepG2 instead of primary liver cells. Related to an earlier study, where we could show the principal suitability of the system for rat primary cells, we here investigated the system's suitability for the human carcinoma cell line HepG2. The carcinoma cells were used in two different types of chip-containing bioreactors. By confocal laser scanning microscopy, we could show that cellular integrity in the chip culture was maintained and that there were no signs of apoptosis as confirmed by the absence of K18 fragmentation. Gene expression analysis of some liver-specific genes revealed a significantly higher expression of the phase II metabolism genes uridine-diphosphate- glucosyl-transferase (UGT1A1) and glutathione-S-transferase (GSTpi1) as a marker. Therefore, we conclude that by using a three-dimensional instead of a conventional monolayer culture system, hepatocellular carcinoma cells display a phenotype that resembles more closely the tissue of origin. | 18,765,895 |
Nano-beta-tricalcium phosphates synthesis and biodegradation: 1. Effect of microwave and SO(4)(2-) ions on beta-TCP synthesis and its characterization. | Nano-sized calcium deficient hydroxyapatite (CDHA) powders with an average particle size less than 100 nm were prepared by a co-precipitation method at low temperature. The initial Ca/P molar ratio was chosen to be less than the stoichiometric ratio of beta-TCP (1.5). Additionally, lowering the temperature and pH values accelerated HPO(4)(2-) incorporation in the CDHA structure. HPO(4)(2-) is considered as an essential source for beta-TCP formation. Sulfate ion doping during the maturation period is proved to be an effective step to eliminate the pyrophosphate P(2)O(7)(2-) phase that results during the calcination of CDHA with Ca/P < 1.5. Furthermore, the heating effect of microwave irradiation resulted in an increase in Ca ion concentration and lowered the CDHA deficiency which affected beta-TCP purity despite its ability to reduce the particle size. A purity of 99.32% beta-TCP with respect to the P(2)O(7)(2-) phase was achieved by increasing the sulfate ion concentration from 2% to 3% and the calcination temperatures from 900 degrees C to 1100 degrees C. | 18,765,896 |
Purification, crystallization and preliminary X-ray analysis of human mannose-binding lectin-associated serine protease-1 (MASP-1) catalytic region. | MASP-1, a multidomain serine protease, is a component of the lectin pathway of complement. Its precise function is unknown, although it seems to enhance the complement-activating capacity of MASP-2, a related enzyme. MASP-1 has also been implicated as playing a role in blood coagulation. It is mostly found associated with mannose-binding lectin (MBL) and ficolins. Early attempts to crystallize MASP-1 failed because of the inhomogeneity of the purified material. MASP-1 was shown by acidic nondenaturing PAGE to be composed of differently charged species, which are most likely to be the products of deamidation occurring during the refolding procedure. Sequential cation-exchange and anion-exchange chromatography resulted in a homogeneous material, which was successfully crystallized. The best crystal diffracted to 2.55 A resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 68.4, b = 70.4, c = 121.4 A. The crystal structure of MASP-1 may help in understanding the function of this mysterious serine protease. | 18,765,903 |
Preliminary X-ray diffraction analysis of YqjH from Escherichia coli: a putative cytoplasmic ferri-siderophore reductase. | YqjH is a cytoplasmic FAD-containing protein from Escherichia coli; based on homology to ViuB of Vibrio cholerae, it potentially acts as a ferri-siderophore reductase. This work describes its overexpression, purification, crystallization and structure solution at 3.0 A resolution. YqjH shares high sequence similarity with a number of known siderophore-interacting proteins and its structure was solved by molecular replacement using the siderophore-interacting protein from Shewanella putrefaciens as the search model. The YqjH structure resembles those of other members of the NAD(P)H:flavin oxidoreductase superfamily. | 18,765,906 |
Crystallization and preliminary X-ray diffraction analysis of the peptidylprolyl isomerase Par27 of Bordetella pertussis. | Proteins with both peptidylprolyl isomerase (PPIase) and chaperone activities play a crucial role in protein folding in the periplasm of Gram-negative bacteria. Few such proteins have been structurally characterized and to date only the crystal structure of SurA from Escherichia coli has been reported. Par27, the prototype of a new group of parvulins, has recently been identified. Par27 exhibits both chaperone and PPIase activities in vitro and is the first identified parvulin protein that forms dimers in solution. Par27 has been expressed in E. coli. The protein was purified using affinity and gel-filtration chromatographic techniques and crystallized in two different crystal forms. Form A, which belongs to space group P2 (unit-cell parameters a = 42.2, b = 142.8, c = 56.0 A, beta = 95.1 degrees ), diffracts to 2.8 A resolution, while form B, which belongs to space group C222 (unit-cell parameters a = 54.6, b = 214.1, c = 57.8 A), diffracts to 2.2 A resolution. Preliminary diffraction data analysis agreed with the presence of one monomer in the asymmetric unit of the orthorhombic crystal form and two in the monoclinic form. | 18,765,910 |
Crystallization and preliminary X-ray diffraction studies of the calcium-binding protein CalD from Streptomyces coelicolor. | Calcium ions play an important regulatory role in eukaryotes. However, the regulatory roles of Ca(2+) in prokaryotes are poorly understood. CalD, an 18 kDa calcium-binding protein from the model actinomycete Streptomyces coelicolor A3(2), was purified and crystallized for structure determination by X-ray crystallography. Crystals of CalD that were suitable for X-ray diffraction were obtained using the hanging-drop vapour-diffusion method and diffraction data were collected in-house to 1.56 A resolution. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 32.9, b = 51.0, c = 87.0 A, alpha = beta = gamma = 90.0 degrees . There is one protein molecule per asymmetric unit. | 18,765,912 |
1,25-Dihydroxy vitamin D3 is an autocrine regulator of extracellular matrix turnover and growth factor release via ERp60-activated matrix vesicle matrix metalloproteinases. | As growth plate chondrocytes mature and hypertrophy, they reorganize their proteoglycan-rich type II collagen extracellular matrix (ECM), involving 1,25(OH)(2)D(3)-dependent regulation of matrix metalloproteinases (MMPs). Stromelysin-1 (MMP-3) and 72-kD gelatinase (MMP-2) are found in extracellular matrix vesicles (MVs) and release and activate ECM-bound latent TGF-beta1 and TGF-beta2, respectively. 1,25(OH)(2)D(3) regulates incorporation of MMP-2 and MMP-3 into MVs and release of these enzymes in the ECM. Plasma membranes (PMs) and MVs contain the 1alpha,25(OH)(2)D(3) membrane receptor ERp60 (protein disulfide isomerase A3), phospholipase A(2) (PLA(2)), PLA(2)-activating protein, the nuclear vitamin D receptor and caveolin-1. 1,25(OH)(2)D(3) secreted by chondrocytes binds MV ERp60, activating PLA(2). Resulting lysophospholipids destabilize MV membranes, releasing active MMPs. We examined 1,25(OH)(2)D(3)-dependent activation of latent TGF-beta1 stored in cartilage ECM. Interestingly, TGF-beta1 regulates 1,25(OH)(2)D(3) production. 1alpha,25(OH)(2)D(3) activates PM protein kinase C (PKC)-alpha via ERp60-dependent PLA(2)-signaling, lysophospholipid production and phospholipase C-gamma. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching MVs in PKC-zeta. Direct activation of MV MMP-3 requires ERp60 based on blocking antibodies and PKC based on inhibitor studies. However, treatment of MVs with 1,25(OH)(2)D(3) decreases MV PKC-zeta activity, suggesting more complex feedback mechanisms, potentially involving MV lipid signaling. Our observations indicate that one role of MVs is to provide MMPs at sites distant from the cells. Chondrocytes secrete 1,25(OH)(2)D(3), which acts directly on MV-membranes via ERp60, releasing MMPs. MMP-specific ECM components are hydrolyzed, resulting in release and activation of growth factors that can act back on the cells. | 18,765,931 |
Magnetocardiography-guided management of an unusual case of isoimmune complete atrioventricular block complicated by ventricular tachycardia. | A fetus who was diagnosed at 25 weeks of gestation with isoimmune AV block presented at 34 weeks with a precipitous fall in ventricular rate and periods of tachycardia. Magnetocardiography revealed the tachycardia to be ventricular. After delivery, nonsustained ventricular tachycardia continued. The baby then successfully paced, and at higher ventricular rates the tachycardia resolved. Five years later the child has normal ventricular function and is doing well. | 18,765,944 |
Perceived stigmatization of children with speech-language impairment and their parents. | Developmental disorders in childhood are generally assumed to have stigmatizing effects. The goal of the present study was to assess whether parents of children with speech-language impairment perceive stigmatization of their child or themselves and which variables influence the degree of negative labeling. The study was based on 362 questionnaires completed by parents of children with speech-language impairment. The questionnaires concerned perceived stigmatization by other children, other adults and family members as a result of the child's developmental problems. In our sample, about 50% of the parents reported negative labeling of their child and about 30% felt they were involved in the stigmatizing process. Parents whose children also had behavioral problems more often reported negative labeling than parents whose children did not. The findings suggest that parents of children with speech-language disorders often perceive stigmatization of their children or themselves. In counseling such families, professionals should therefore address stigmatization and its consequences as a separate and important issue. | 18,765,946 |
Transforming growth factor-beta signaling in thoracic aortic aneurysm development: a paradox in pathogenesis. | Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behavior, pose a serious health risk characterized by the lack of medical treatment options and high rates of surgical morbidity and mortality. Independent of the inciting stimuli (biochemical/mechanical), TAA development proceeds by a multifactorial process influenced by both cellular and extracellular mechanisms, resulting in alterations of the structure and composition of the vascular extracellular matrix (ECM). While the role of enhanced ECM proteolysis in TAA formation remains undisputed, little attention has been focused on the upstream signaling events that drive the remodeling process. Recent evidence highlighting the dysregulation of transforming growth factor-beta (TGF-beta) signaling in ascending TAAs from Marfan syndrome patients has stimulated an interest in this intracellular signaling pathway. However, paradoxical discoveries have implicated both enhanced TGF-beta signaling and loss of function TGF-beta receptor mutations, in aneurysm formation; obfuscating a clear functional role for TGF-beta in aneurysm development. In an effort to elucidate this subject, TGF-beta signaling and its role in vascular remodeling and pathology will be reviewed, with the aim of identifying potential mechanisms of how TGF-beta signaling may contribute to the formation and progression of TAA. | 18,765,947 |
The phenomenology of the psychotic break and Huxley's trip: substance use and the onset of psychosis. | While considerable research attention has been devoted to the causal relationship between substance use and psychosis, the phenomenology of the association between the two has largely been ignored. This is a significant shortcoming, because it blinds researchers to the possibility that there may be elements of the subjective experience of substance use and psychosis that contribute to their apparent relationship in empirical studies. The current paper examines the phenomenology of the onset of psychosis and the phenomenology of substance intoxication through consideration of two texts: Sass's account of the phenomenology of psychosis onset and Huxley's account of the experience of hallucinogenic intoxication. Sass's account of psychosis onset includes four components: Unreality, Fragmentation, Mere Being, and Apophany. The analysis reveals significant parallels - and also some differences - between this account and the phenomenology of substance intoxication. We discuss the implications of this for the causal relationship between psychosis and substance use and suggest several ways of understanding the overlapping phenomenologies. This includes the suggestion of a shared factor, perhaps best described as psychotic-like experience, which seems to involve a breakdown of the sign-referent relationship and relationship with the common-sense, practical world. However, in the onset of psychosis, this breakdown is primarily experienced as a sense of alienation from self and world, whereas in the hallucinogenic state a sense of mystical union and revelation seems predominant. Further research may extend this analysis by looking at experiences with other drugs, particularly cannabis, and by examining the phenomenology of psychotic disorder beyond the first episode. | 18,765,960 |
DSM-IV personality disorders and their axis I correlates in the South African population. | The prevalence of personality disorders (PD) in the South African population is largely unknown. Thus, we undertook to estimate prevalence, demographic correlates, co-morbidity and treatment rates of DSM-IV PD among South Africans. A three-stage probability sample design was used. Of the 4,433 interviews obtained, based on quality control criteria, 4,315 interviews were retained for analysis. All participants were screened for PD and axis I disorders with the World Health Organisation Composite International Diagnostic Interview. The multiple imputation method was then used to estimate prevalence. The multiple imputation prevalence estimate in the total sample was 6.8%. All three PD clusters were significantly co-morbid with each other and with other axis I disorders. Male gender was the only significant predictor of PD. Of note was the finding that less than one fifth of participants with a possible PD diagnosis had received treatment for a mental health or substance abuse problem in the previous 12 months. The high co-morbidity of PD with axis I disorders in South Africa is consistent with previous reports elsewhere. However, more research is indicated to determine the reasons for the higher prevalence of cluster A disorders than of cluster B and C disorders in this population. | 18,765,961 |
Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. | Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) is an albumin-bound 130-nm particle form of paclitaxel that demonstrated higher efficacy and was well tolerated compared with solvent-based paclitaxel (Taxol) and docetaxel (Taxotere) in clinical trials for metastatic breast cancer. Nab-paclitaxel enhances tumor targeting through gp60 and caveolae-mediated endothelial transcytosis and the association with the albumin-binding protein SPARC (secreted protein, acidic and rich in cysteine) in the tumor microenvironment. The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer has been shown to correlate with resistance to paclitaxel. To evaluate the importance of HER2 and SPARC status in determining the relative efficacy of nab-paclitaxel compared with polysorbate-based docetaxel, nude mice bearing six different human tumor xenografts were treated with nab-paclitaxel (MX-1: 15 mg/kg, once a week for 3 weeks; LX-1, MDA-MB-231/HER2+, PC3, and HT29: 50 and 120 mg/kg, every 4 days three times ; MDA-MB-231: 120 and 180 mg/kg, every 4 days three times) and polysorbate-based docetaxel (15 mg/kg). HER2 and SPARC status were analyzed by RT-PCR and immunohistochemical staining. MDA-MB-231 and MX-1 breast and LX-1 lung cancers were HER2 negative and low in SPARC expression. Nab-paclitaxel at submaximum-tolerated dosage was significantly more effective than polysorbate-based docetaxel at its maximum-tolerated dosage in these three HER2-negative tumors. The HER2-positive tumors had variable SPARC expression, with MDA-MB-231/HER2+ <PC3 <HT29. In these HER2-positive tumors, nab-paclitaxel was equal to or better than polysorbate-based docetaxel in tumors with medium to high SPARC levels (PC3 and HT29), but not in MDA-MB-231/HER2+ tumors with low SPARC expression. These results demonstrated that the relative efficacy of nab-paclitaxel was significantly higher compared with polysorbate-based docetaxel in HER2-negative tumors (three of three) and in HER2-positive tumors with high levels of SPARC. HER2 and SPARC expression may be useful biomarkers in determining antitumor effectiveness for taxanes. | 18,766,004 |
Auditory frequency-following responses in rat ipsilateral inferior colliculus. | Auditory frequency-following responses (FFRs) are sustained potentials based on phase-locked neural activity preserving low-frequency information. Some neurons in rat inferior colliculus are excited by stimuli at either ear. This study shows that FFRs in inferior colliculus can be elicited by presenting pure tone bursts with frequencies from 225 to 4025 Hz at the ipsilateral ear in anesthetized rats. Moreover, chemical block of glutamate transmissions in the contralateral inferior colliculus markedly reduced the ipsilaterally driven FFRs, which, however, were significantly enhanced by blocking the contralateral dorsal nucleus of the lateral lemniscus. Thus, FFRs in inferior colliculus to ipsilateral stimulation were facilitated by excitatory projections from the contralateral inferior colliculus but suppressed by inhibitory projections from the contralateral dorsal nucleus of the lateral lemniscus. | 18,766,015 |
FMRI/ERP of musical syntax: comparison of melodies and unstructured note sequences. | To date, the neural correlates of musical syntax processing have been investigated mainly by means of paradigms in which isolated chords are made incongruent with the harmonic context. Here, we present results obtained contrasting unfamiliar one-part piano melodies with unstructured note sequences, comparable in pitch and rhythm but devoid of any syntactic structure. This paradigm indexes a superset of the cognitive functions involved in processing of harmonic rules. Using functional magnetic resonance imaging, differential activation of a bilateral cortical network comprising the inferior frontal gyrus, superior temporal gyrus and premotor cortex was found. Using event-related potentials, the N2 evoked by each note in melodies was found to have longer latency and a more frontal distribution than that evoked in unstructured sequences. | 18,766,016 |
Breast reduction: does the tumescent technique affect reimbursement? | Breast reduction is a very common procedure within the field of plastic surgery, with many techniques. These techniques include differences in the location of the pedicles and of the scars. Another variation on the technique for breast reduction relates to preoperative infiltration of an epinephrine solution to reduce blood loss and operative time. The authors' technique for breast reduction and its effect on insurance reimbursement has not previously been discussed in a large prospective study. The authors performed a prospective study to compare a cohort of 50 patients undergoing a traditional breast reduction without infiltration of epinephrine followed by electrocautery for resection versus 50 patients receiving tumescent infiltration of epinephrine followed by sharp resection. The patients who underwent the tumescent technique for breast reduction had shorter operative times and similar blood loss and pain compared with the traditional technique. The use of tumescence did not cause a significant difference in the weight of the amount resected when compared with the dry, pathologic weight. In the first large prospective cohort study involving this technique, the authors can demonstrate the many advantages of the tumescent technique and refute their concern that tumescence can cause inaccurate weight measurements that might interfere with insurance reimbursement based on resected weight. | 18,766,030 |
Value of blood adipose tissue hormones concentration--adiponectin, resistin and leptin in the prediction of major adverse cardiac events (MACE) in 1-year follow-up after primary percutaneous coronary intervention in ST-segment elevation acute myocardial infarction. | The objective of the study was to assess the impact of adipokines on the future major adverse cardiac events (MACE) in patients with acute myocardial infarction. Subjects were 77 men with first, ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention in whom data were available after one year follow-up. Baseline clinical and angiographic data were collected, blood level of C-reactive protein, uric acid, fasting glucose, lipid profile, adiponectin, resistin and leptin and left ventricular ejection fraction on echocardiography were assessed. MACE was defined as cardiac death, nonfatal myocardial infarction, hospitalization for angina or heart failure. 12% of patients experienced MACE. As revealed by univariate logistic regression analysis predictors of MACE were diabetes, multivessel disease, ejection fraction, blood C-reactive protein and adiponectin level. In multivariable analysis diabetes (OR=22.19, 95%CI 1.22-402.19; p=0.0360), lower left ventricular ejection fraction (OR=0.78, 95%CI 0.63-0.98; p=0.0298) and lower adiponectin level (OR=0.19, 95%CI 0.04-0.90; p=0.0362) were independent negative predictors of MACE. The optimal value of adiponectin for predicting MACE was 4.23 microg/ml. CONCLUSION. In male patients with myocardial infarction undergoing primary percutaneous coronary intervention, a baseline blood adiponectin but not resistin or leptin is independently predictive of MACE. The other prognostic factors are diabetes mellitus and left ventricular ejection fraction. | 18,766,137 |
Adjunctive aripiprazole decreased metabolic side effects of clozapine treatment. | Clozapine is an atypical antipsychotic indicated for the treatment of refractory schizophrenia. Clozapine treatment is associated with the metabolic side effects. Weight gain, hyperlipidemia and hyperglycemia are the risk factors for onset of diabetes and cardiovascular disorders. We report a case vignette of a patient in whom the decrease in negative and general psychopathology after adjunctive aripiprazole appeared simultaneously with a reduction of clozapine-induced increase in weight and metabolic measures. Combined application of clozapine and aripiprazole is in accordance with a neurobiological rationale and appears to be a safe and well tolerated. | 18,766,167 |
Additional metabolic effects of adding GH receptor antagonist to long-acting somatostatin analog in patients with active acromegaly. | Somatostatin analogs, dopamine agonists and GH-receptor antagonist--pegvisomant are used in medical therapy of acromegaly. Since pegvisomant has not antitumor effect, the combination of pegvisomant and somatostatin analog could be an attractive option. Aim of study was to assess the effects of pegvisomant and octreotide LAR treatment on GH and IGF-1 levels, and glucose tolerance in acromegaly, and to assess efficacy and tolerability of rapid (after 7 days) pegvisomant dose titration. Six patients (4 men, 2 women) aged 47.5 years (median) with active acromegaly, after neurosurgery failed, resistant to maximal doses of octreotide, received daily 10-20 mg pegvisomant throughout 2 weeks. They were given octreotide LAR 30 mg monthly for at least 6 months before pegvisomant therapy. Clinical symptoms, GH, IGF-1, fasting glucose and insulin levels were measured on the 0, 8th and 15th day of pegvisomant therapy. On the 8th day pegvisomant dose was titrated based on serum IGF-1 level. IGF-1 levels reduced from 739 at the beginning to 418 ng/ml (medians) on the 15th day of treatment and normalized in one patient. These changes were associated with improvement of glucose metabolism. One diabetic patient could even stop insulin therapy. Pegvisomant is an attractive adjuvant therapy for controlling acromegaly. Pegvisomant improves insulin sensitivity as well as glucose tolerance. The GH receptor antagonist is good option for patients with active acromegaly coexistent with disturbances of glucose metabolism, especially with diabetes mellitus. Rapid pegvisomant dose increasing to efficient or maximal is well tolerated and effective. | 18,766,168 |
Recombinant oncolytic poliovirus eliminates glioma in vivo without genetic adaptation to a pathogenic phenotype. | Many viruses, either naturally occurring or as a result of genetic manipulation, exhibit conditional replication in transformed cells. This principle is the basis for experimental therapeutic approaches exploiting the oncolytic potential of such agents without the danger of collateral damage to resistant normal tissues. One of the potential obstacles to these approaches is the possibility of genetic adaptation of oncolytic viruses upon replication in susceptible tumor tissues. Genetic variation can reverse genetic manipulations of parental viral genomes that determine attenuation of virulence, selective tumor cell tropism or other desirable traits. Alternatively, it may convey new properties not originally associated with parental strains, e.g., adaptation to a human host range. We examined genetic stability of an oncolytic nonpathogenic poliovirus recombinant considered for therapy of recurrent glioblastoma multiforme (GBM). This was done by serial passage experiments in glioma xenografts in vivo and investigation of phenotypic and genotypic markers of attenuation. Intratumoral inoculation of oncolytic poliovirus produced efficient tumor regress and elimination without altering temperature-sensitive growth, selective cytotoxicity, or genetic markers of attenuation of virus recovered from inoculated animals. Our studies demonstrate that active viral oncolysis of malignant glioma does not alter the conditional replication properties of oncolytic nonpathogenic poliovirus recombinants. | 18,766,173 |
Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group. | Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse. | 18,766,186 |
Green tea consumption and lung cancer risk: the Ohsaki study. | We examined the risk of lung cancer in relation to green tea consumption in a population-based cohort study in Japan among 41,440 men and women, aged 40-79 years, who completed a questionnaire in 1994 regarding green tea consumption and other health-related lifestyle factors. During the follow-up period of 7 years (from 1995 to 2001), 302 cases of lung cancer were identified, and the Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The multivariable-adjusted HRs of lung cancer incidence for green tea consumption of 1 or 2, 3 or 4, and 5 or more cups/day as compared to less than 1 cup/day were 1.14 (95% CI: 0.80-1.62), 1.18 (95% CI: 0.83-1.66), and 1.17 (95% CI: 0.85-1.61), respectively (P for trend=0.48). This cohort study has found no evidence that green tea consumption is associated with lung cancer. | 18,766,189 |
Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer. | Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age- and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml(-1) has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin-antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group. | 18,766,191 |
Quantitative evaluation of microvascular density after stroke in rats using MRI. | We investigated vascular changes after stroke using magnetic resonance imaging (MRI) microvascular density (MVD) measurement. T(2) and T(2)(*) were measured in eight rats before and after injecting an intravascular superparamagnetic iron oxide contrast agent to derive the corresponding transverse relaxation shift. Reliability of MRI for measurement of MVD was compared with corresponding sections immunostained with von Willebrand factor (vWF) 2 weeks after stroke. The intracorrelation coefficient (ICC) and its 95% lower bound (LB) was high in the ischemic recovery region (ICC=0.753), moderate in the contralateral area of normal brain tissue (ICC=0.70), and low in the ischemic core (ICC=0.24). A very good agreement (ICC=0.85) and correlation (r=0.90) were observed using only the recovery region and normal contralateral hemisphere (ICC=0.85; 95% LB=0.78; P<0.05). The mean MRI MVD in the center of the core lesion (26+/-9 per mm(2)) was lower than in the recovery region (209+/-60 per mm(2)) or contralateral normal hemisphere (313+/-32 per mm(2)). However, large errors in MRI MVD were encountered in the ischemic core. Our data demonstrate that MRI MVD measurements can quantitatively evaluate microvascular changes in the brain tissue after stroke, if the MVD is not extremely low as in the ischemic core. | 18,766,197 |
A mechanistic investigation into the elimination of phosphonium salts from rhodium-TRIPHOS complexes under methanol carbonylation conditions. | Phosphine modified rhodium complexes are currently the topic of considerable research as methanol carbonylation catalysts, but often suffer from poor stability. This paper reports on an investigation into how coordination mode affects the elimination of phosphonium salts from rhodium complexes, namely [trans-RhCl(CO)(PPh3)2] 1, [RhCl(CO)(dppe)] 2, [RhCl(CO)(dppb)]2 3, [Rh(TRIPHOS)(CO)2]Cl 4. These complexes are all potential pre-catalysts for methanol carbonylation. The reaction of these complexes with methyl iodide at 140 degrees C under both N2 and CO atmospheres has been studied and has revealed clear differences in the stability of the corresponding Rh(III) complexes. In contrast to both monomeric 2 and dimeric 3 that react cleanly with CH3I to give stable Rh(III) acetyl complexes, 4 forms a novel bidentate complex after the elimination of the one arm of the ligand as a quaternised phosphonium salt. The structure of this complex has been determined spectroscopically and using X-ray crystallography. The mechanism of formation of this novel complex has been investigated using 13CH3I and strong evidence that supports a dissociative mechanism as the means of phosphine loss from the rhodium centre is provided. | 18,766,227 |
Quantum algorithm for obtaining the energy spectrum of molecular systems. | Simulating a quantum system is more efficient on a quantum computer than on a classical computer. The time required for solving the Schrödinger equation to obtain molecular energies has been demonstrated to scale polynomially with system size on a quantum computer, in contrast to the well-known result of exponential scaling on a classical computer. In this paper, we present a quantum algorithm to obtain the energy spectrum of molecular systems based on the multiconfigurational self-consistent field (MCSCF) wave function. By using a MCSCF wave function as the initial guess, the excited states are accessible. Entire potential energy surfaces of molecules can be studied more efficiently than if the simpler Hartree-Fock guess was employed. We show that a small increase of the MCSCF space can dramatically increase the success probability of the quantum algorithm, even in regions of the potential energy surface that are far from the equilibrium geometry. For the treatment of larger systems, a multi-reference configuration interaction approach is suggested. We demonstrate that such an algorithm can be used to obtain the energy spectrum of the water molecule. | 18,766,235 |
A kinetic model for photoswitching of magnetism in the high spin molecule [Mo(IV)(CN)2(CN-Cu(II)(tren))6](ClO4)8. | The heptanuclear complex [Mo(IV)(CN)2(CN-CuL)6]8+ switches from a paramagnetic dark state corresponding to six spin-1/2 Cu(II) ions to a predominantly high spin S = 3 state, on prolonged irradiation with 406 nm laser radiation at low temperature. The system returns to a paramagnetic state on warming to room temperature. The temperature dependence of the chiMT vs. T curve depends upon duration of irradiation. An earlier microscopic model showed that the excitation cross sections in different spin manifolds are similar in magnitude and that photomagnetism is not due to preferential excitation to the S = 3 state. In this paper, we attribute photomagnetism to a long lived S = 3 charge transfer excited state for which there appears to be sufficient experimental evidence. Based on this postulate, we model the photomagnetism by employing a kinetic model which includes internal conversions and intersystem crossings. The key feature of the model is the assumption of the existence of two kinds of S = 3 states: one of which has no direct pathway for internal conversion and the other characterized by slow kinetics for internal conversion to the low-energy states. The trapped S = 3 state can decay via a thermally activated barrier to the other S = 3 state. The experimental chiMT vs. T for two different irradiation times are fitted using Arrhenius dependence of the rate constants in the model. | 18,766,245 |
Clinical implications of aspirin resistance. | Aspirin reduces major atherothrombotic events across a wide spectrum of patients with atherosclerotic disease. The occurrence of ischemic events despite of aspirin treatment is a failure of therapy, often denoted 'clinical aspirin resistance'. This is distinguished from laboratory assays showing an insufficient inhibition of platelet function, which indicate 'laboratory aspirin resistance'. Laboratory aspirin resistance has been reported in up to 60% of patients after stroke or peripheral arterial disease, up to 70% in stable coronary heart disease and even up to 80% in acute myocardial infarction. However, this data must be interpreted carefully because of small sample sizes and potential confounding factors such as compliance, co-morbidities and large differences between the laboratory methods used for detection. During the past years, evidence has accumulated that laboratory aspirin resistance is associated with an increased incidence of major atherothrombotic events, with an up to 13-fold increased risk of events in patients with cardiovascular disease. Thus, an individualized antiplatelet therapy will have to consider the possibility of aspirin resistance, and the identification of aspirin non-responders may improve antiplatelet therapy in future. Whether an increased dose of aspirin or another antiplatelet drug (e.g. clopidogrel) instead or in addition to aspirin should be given is unclear. Prospective trials are underway which address this issue. This review gives an overview on the various clinical studies that have investigated the prevalence and clinical importance of laboratory aspirin resistance. Moreover, therapeutic options, as well as future perspectives are discussed. | 18,766,252 |
Should female relatives of factor V Leiden carriers be screened prior to oral contraceptive use? A cost-effectiveness analysis. | Venous thromboembolism (VTE) is three-fold higher among FV Leiden (FVL) carriers receiving oral contraceptives (OCPs) than in the general population. FVL screening, however, is not routinely performed before prescribing OCP, and the cost-effectiveness of this strategy is unknown. A decision tree model was constructed to evaluate FVL screening and prophylactic anticoagulation (AC) strategies in female relatives of FVL carriers. In the model, AC was low molecular weight heparin, given warfarin embryopathy risks. VTE morbidity, mortality, and other clinical parameters were obtained from published studies. Drug costs were based on average wholesale price, and counseling included VTE risk with OCP use and FVL status. Outcomes included medical costs, effectiveness measured as quality-adjusted-life-years (QALY), and the incremental cost-effectiveness ratio (ICER) over 30 years, with cost and effectiveness discounted at 3%/year. FVL screening and counselling without prophylactic AC cost less and was more effective than no screening in this population, but was less effective than screening, counselling, and prophylaxis during high-risk periods, which gained 0.083 QALY, for an ICER of $147/QALY gained. Screening with counselling and long-term AC cost $3,536 with minimal QALY gain and an ICER >$600,000/QALY. Screening, OCP counseling, and prophylactic AC during high-risk periods was favoured and cost <$20,000/QALY, unless: (a) high-risk prophylaxis cost >$4,231 (base $932), (b) long-term prophylaxis cost <$1199 (base $6,546), or (c) VTE relative risk reduction with prophylaxis was <21% (base 90%). In conclusion, screening, counselling and prophylactic AC during high-risk periods in female relatives of FVL carriers is an economically favourable strategy. | 18,766,261 |
Heparin-induced antibodies and cardiovascular risk in patients on dialysis. | The clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thrombocytopenia or any of the four clinical outcomes over a mean follow-up of 3.6 years, with hazard ratios for arterial cardiovascular events of 0.98 (95% confidence interval 0.70-1.37), venous thromboembolism 1.39 (0.17-11.5), vascular access occlusion 0.82 (0.40-1.71), and mortality 1.18 (0.85-1.64). Chronic intermittent heparin exposure was associated with a high seroprevalence of HIA. In dialysis patients these antibodies were not an independent risk factor for cardiovascular events and mortality. Our data do not suggest that dialysis patients should be monitored for HIA antibodies in the absence of thrombocytopenia. | 18,766,268 |
[Prevalence of low visual acuity and ophthalmological disorders in six-year-old children from Santa Fe city]. | Changes in children visual acuity that are not treated carry a high risk of irreversible consequences. To determine the prevalence of low visual acuity and to diagnose the ophthalmologic diseases that cause it in six-year-old children from Santa Fe City, Argentina. Observational, descriptive and transversal design. Visual acuity is defined as the eye's capacity to distinguish separate points and to recognize shapes. It was determined using the Snellen table for farsighted vision on 177 six-year-old children who attended four elementary schools in Santa Fe City. An ophthalmologic examination was performed on those who had low visual acuity and their mothers were interviewed to ascertain the pathological background of their children. The prevalence of low visual acuity was 10.7% (n= 19). The prevalence of amblyopia was 3.9%. Refraction errors were the only cause of low visual acuity. Astigmatism was predominantly frequent. The most frequent pathological backgrounds were: ocular infections, premature birth, history of malnutrition and maternal use of tobacco. The prevalence of low visual acuity found in this study is lower than the one informed in most other studies. This data require confirmation by further studies. | 18,766,279 |
Depression, abuse and its relationship to interstitial cystitis. | This study evaluated the prevalence of depression, sexual abuse, and physical abuse among women diagnosed with interstitial cystitis (IC). One hundred forty-one subjects completed the validated Beck's Depression Inventory II Questionnaire (BDI-II) and the validated Drossman Abuse Questionnaire. Ninety-seven (69%) subjects scored 14 or higher on the BDI-II, corresponding to depression. When compared to the US prevalence of 9%, this was significantly higher. Fifty-one subjects (36%) reported sexual abuse which is higher than the US average. The prevalence of childhood sexual abuse in the sample was not significantly different than the US average. The prevalence of physical abuse in the sample was not statistically different than the US average. Women with IC appear to have a higher prevalence of depression and sexual abuse than the general population. Women with IC should be screened for depression and abuse and referred to a mental health expert as necessary for treatment. | 18,766,291 |
Nightshift work and fracture risk: the Nurses' Health Study. | Nightshift work suppresses melatonin production and has been associated with an increased risk of major diseases including hormonally related tumors. Experimental evidence suggests that light at night acts through endocrine disruption likely mediated by melatonin. To date, no observational study has addressed the effect of night work on osteoporotic fractures, another condition highly sensitive to sex steroid exposure. Our study, to our knowledge, the first to address this question, supports the hypothesis that nightshift work may negatively affect bone health, adding to the growing list of ailments that have been associated with shift work. We evaluated the association between nightshift work and fractures at the hip and wrist in postmenopausal nurses. The study population was drawn from Nurses' Health Study participants who were working full or part time in nursing in 1988 and had reported their total number of years of rotating nightshift work. Through 2000, 1,223 incident wrist and hip fractures involving low or moderate trauma were identified among 38,062 postmenopausal women. We calculated multivariate relative risks (RR) of fracture over varying lengths of follow-up in relation to years of nightshift work. Compared with women who never worked night shifts, 20+ years of nightshift work was associated with a significantly increased risk of wrist and hip fractures over 8 years of follow-up [RR = 1.37, 95% confidence interval (CI), 1.04-1.80]. This risk was strongest among women with a lower body mass index (<24) who never used hormone replacement therapy (RR = 2.36; 95% CI, 1.33-4.20). The elevated risk was no longer apparent with 12 years of follow-up after the baseline single assessment of nightshift work. Long durations of rotating nightshift work may contribute to risk of hip and wrist fractures, although the potential for unexplained confounding cannot be ruled out. | 18,766,292 |
[Worsening in patients treated in acute stroke units--results of the Austrian Stroke Unit Registry]. | Up to one-third of patients admitted to a hospital due to an ischemic stroke or a transient ischemic attack show clinical worsening of symptoms in the first hours to days after admission. We analyzed on the basis of a large patient group the frequency of minor or major worsening and the possible predictors for worsening. In the nationwide Austrian Stroke Unit Registry, 11616 patients with ischemic stroke or transient ischemic attack and a known NIHSS on admission and discharge from the stroke unit were recorded between March 2003 and February 2007. 363 (3.13%) of these patients showed a minor deterioration (NIHSS difference between admission and discharge 2 or 3 points) and 559 (4.81%) a major deterioration (NIHSS difference 4 or more points). In a logistic regression model, diabetes mellitus [OR (95%CI) 1.8 (1.3-2.4)], arterial hypertension [1.8 (1.2-2.8)], a cardiogen embolic event [1.6 (1.1-2.4)], and a large vessel disease [1.7 (1.2-2.6)] were independent predictors for a minor deterioration. Predictors for a major deterioration were a higher age [1.0 (1.0-1.1)], hypertension [1.4 (1.1-2.0)], diabetes mellitus [1.5 (1.2-1.9)], a higher NIHSS at admission [1.1 (1.0-1.1)], and a large vessel disease [1.8 (1.3-2.4)]. This underlines the importance of early diagnostic workup and risk evaluation in order to prevent also early deterioration by immediate initiation of dedicated therapeutic approaches. | 18,766,311 |
Molecular mechanisms underlying the onset of degenerative aortic valve disease. | Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. | 18,766,323 |
Activation of somatostatin receptors in the globus pallidus increases rat locomotor activity and dopamine release in the striatum. | Somatostatin and its receptors have been localized in brain nuclei implicated in motor control, such as the striatum, nucleus accumbens, ventral pallidum, and globus pallidus (GP). The objective of this study was to investigate the role of somatostatin receptors (sst(1,2,4)) in the GP on dopamine (DA)-mediated behaviors, such as locomotor activity, and to examine the GP-striatum circuitry by correlating the effect of somatostatin in the GP with the release of DA in the striatum. Animals received saline, somatostatin (60, 120, 240 ng/0.5 microl per side) or the following selective ligands: L-797,591 (sst(1) analog, 60, 120, 240 ng/0.5 microl per side), L-779,976 (sst(2) analog, 120, 240, 480 ng/0.5 microl per side), L-803,087 (sst(4) analog; 120, 240, 480 ng/0.5 microl per side), L-796,778 (sst(3) analog, 240 ng/0.5 microl per side), SRA-880 (sst(1) selective antagonist + somatostatin, 120 ng/0.5 microl per side), CYN154806 (sst(2) selective antagonist + somatostatin, 120 ng/0.5 microl per side) bilaterally in the GP of the rat. Locomotor activity was measured for 60 min. The effect of somatostatin, administered intrapallidally, on the extracellular concentrations of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the striatum was also studied in the behaving rat using in vivo microdialysis methodology. Somatostatin increased the locomotor activity of the rat in a dose-dependent manner. This effect was mediated by activation of the sst(1), sst(2), and sst(4) receptors. Selective sst agonists increased locomotor activity in a statistical significant manner, while selective sst(1) and sst(2) antagonists reversed the somatostatin-mediated locomotor activity to control levels. DA levels increased in the striatum after intrapallidal infusion of somatostatin (240 ng/side). These data provide behavioral and neurochemical evidence of the functional role of somatostatin receptors in the GP-striatum circuitry. | 18,766,330 |
Dose-response effect of serum butyrylcholinesterase activity after clinical doses of pancuronium. | Low-dose pancuronium is known to affect serum cholinesterase activity (BChE); however, the dose-response effect of clinical doses of pancuronium on BChE has not been investigated. Thirteen ASA I-II patients scheduled for elective surgery requiring muscle relaxation were enrolled in this study. All patients had normal BChE before surgery. Incremental doses of pancuronium (10, 20, 50, and 100 microg/kg) were injected in accordance with surgical needs every 45 min. BChE was measured 3 min after injection by an automatic colorimetric method. BChE decreased significantly in all except one patient in comparison to the baseline (P < 0.05). However all values remained within normal clinical range. A dose of 100 microg/kg yielded significant decrease in comparison to 10 microg/kg but not to other dosages. Linear regression was not significant for the dose-response relationship (P = 0.05). After clinical incremental doses of pancuronium, BChE remained within clinical range. | 18,766,333 |
Interethnic differences of PEPT2 (SLC15A2) polymorphism distribution and associations with cephalexin pharmacokinetics in healthy Asian subjects. | The aims of this study were to characterize the population frequency of PEPT2 (SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects. PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally) pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were subsequently genotyped for their PEPT2 polymorphisms. In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and 0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C (max) of cephalexin was significantly lower in the Chinese (29.80 +/- 4.09 microg ml(-1)) population than in the Asian Indian one (33.29 +/- 4.97 microg ml(-1); P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups. PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are needed. | 18,766,334 |
X-ray diffraction analysis of urinary calculi: need for heat treatment. | Although X-ray diffraction (XRD) is the most reliable method for analysis of urinary stones, it has its specific limitations. It fails to detect amorphous phases, cannot distinguish between chemically different phases having identical lattice geometry (e.g., brushite CaHPO4.2H2O and gypsum CaSO4.2H2O) and may miss some phases (e.g., apatite and calcium urates) due to peak overlaps. XRD of urinary stones was performed using a DRON 2.0 diffractometer with CuKalpha radiation and repeated after calcining the sample, preferably with weighing. XRD of the calcined samples enabled detection of amorphous magnesium phosphates, poor crystallized apatite mixed with struvite, weddellite and/or organic matter, hidden organic calcium salts mixed with uric acid; unambiguously discriminated between brushite and gypsum, struvite and its potassium analogue; confirmed presence of quartz in one stone. Statistical study of 341 samples from Rostov region has shown that three-phase mixtures are most frequent (32.3%). Redoing XRD phase analysis after heat treatment, preferably at 500 and/or 900 degrees C, considerably enhances capabilities of the method due to (i) avoiding peak overlaps; (ii) crystallization of amorphous phases; (iii) concentrating minority inorganic components in organic stones; (iv) different decomposition products from indistinguishable phases; (v) semi-quantitative information from the weight loss data. | 18,766,336 |
Weakly nonlinear analysis of a hyperbolic model for animal group formation. | We consider an one-dimensional nonlocal hyperbolic model for group formation with application to self-organizing collectives of animals in homogeneous environments. Previous studies have shown that this model displays at least four complex spatial and spatiotemporal group patterns. Here, we use weakly nonlinear analysis to better understand the mechanisms involved in the formation of two of these patterns, namely stationary pulses and traveling trains. We show that both patterns arise through subcritical bifurcations from spatially homogeneous steady states. We then use these results to investigate the effect of two social interactions (attraction and alignment) on the structure of stationary and moving animal groups. While attraction makes the groups more compact, alignment has a dual effect, depending on whether the groups are stationary or moving. More precisely, increasing alignment makes the stationary groups compact, and the moving groups more elongated. Also, the results show the existence of a threshold for the total group density, above which, coordinated behaviors described by stationary and moving groups persist for a long time. | 18,766,343 |
Evolution of lamellar macular hole studied by optical coherence tomography. | To study the natural course of lamellar macular hole (LMH) as examined by optical coherence tomography (OCT) in a noncomparative observational case series. Forty-one eyes of 41 patients with LMH were included in this analysis. Baseline and final OCT findings related to LMH diameter, foveal thickness and visual acuity (VA) were collected and compared. Mean follow-up was 37.1 months. Main outcome measures were best-corrected visual acuity (BCVA), diameter of the LMH opening, foveal thickness, epiretinal membrane (ERM), posterior vitreous detachment (PVD) and vitreoretinal traction. The diameter of the LMH increased by an average of 13.7%. A statistically significant association was found between the LMH diameter increase and the presence of ERM. The mean foveal thickness depicted a statistically significant decrease between the initial and the final examination. The decrease of the foveal thickness showed to correlate with visual acuity deterioration. BCVA was stable in 30 (78%) and deteriorated in 11 (22%) cases. In eight of the 11 cases, the visual acuity deterioration ranged from 2 to 15 letters. We identified an increase of LMH diameter related to the presence of ERM and a decrease of the foveal thickness within a period of observation which ranged from 24 to 54 months (mean 37.1 months). | 18,766,367 |
[Posttraumatic gusher phenomenon following fracture of the petrous bone]. | The gusher phenomenon is a very rare complication that may occur during stapedectomy or cochleostomy. A sudden perilymphatic flow of cerebrospinal fluid can be seen following platinotomy. The cause is an abnormal connection between subarachnoid and perilymphatic spaces due to congenital malformation, leading to an abnormally wide cochlear aqueduct or due to an internal auditory canal fistula. We describe a case of posttraumatic gusher phenomenon after a fracture of the petrous bone. | 18,766,399 |
"When strangers meet": John Bowlby and Harry Harlow on attachment behavior. | From 1957 through the mid-1970s, John Bowlby, one of the founders of attachment theory, was in close personal and scientific contact with Harry Harlow. In constructing his new theory on the nature of the bond between children and their caregivers, Bowlby profited highly from Harlow's experimental work with rhesus monkeys. Harlow in his turn was influenced and inspired by Bowlby's new thinking. On the basis of the correspondence between Harlow and Bowlby, their mutual participation in scientific meetings, archival materials, and an analysis of their scholarly writings, both the personal relationship between John Bowlby and Harry Harlow and the cross-fertilization of their work are described. | 18,766,423 |
Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. | This study assessed the safety and preliminary efficacy of the interleukin-1 receptor antagonist anakinra in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). Eighty-six patients entered a 12-week open-label run-in phase (1 mg/kg anakinra daily, < or =100 mg/day). Fifty responders were randomized to anakinra or placebo in a 16-week blinded phase, followed by a 12-month open-label extension (N = 44). Due to low enrollment, the primary endpoint was changed from efficacy to safety. The incidence and nature of adverse events were similar across all study phases, with the exception of injection site reactions, which were mild to moderate and decreased with time. Anakinra produced a nonsignificant (P = 0.11) reduction in disease flares compared with placebo. When normalized to 1 mg/kg dose, anakinra plasma concentrations were similar to values in adult patients with rheumatoid arthritis. These results indicate that anakinra 1 mg/kg once daily (< or =100 mg/day) is safe and well tolerated in patients with JRA. | 18,766,426 |
Major influences on nutrient intake in pregnant New Zealand women. | To investigate factors associated with maternal diet during pregnancy and rank these in order of influence using data from a prospective cohort of 196 pregnant women, aged between 18 and 35 years of mostly European origin. Anthropometric measurements were taken, questionnaires administered and 16 days of weighed diet intakes recorded, eight in the fourth and eight in the seventh month of pregnancy. Twenty four hours activity records were kept for 3 days at these times. Factors investigated were education, age, occupational status, welfare dependence, smoking, number of children, morning sickness, activity level, height, weight, body mass index, and sum of skinfolds. Univariate analyses showed median weight of food and nutrient intakes were significantly lower in the less educated, the young, welfare dependants, smokers, and those who vomited during pregnancy. Almost all subjects had intakes of Vitamin D, folate, iron, and selenium below the estimated average requirement. Multivariate analyses of each nutrient against all predictors showed that in decreasing order of importance, education, maternal height, welfare dependence, smoking, and morning sickness had the greatest overall effect on the women's diets, mostly through their influence on energy intake. Age and number of children had less association with nutrient intake but along with education had a strong association with energy adjusted quality of diet. Weight and activity had weak associations with the quantity and quality of intake. After adjusting for energy intake, morning sickness ceased to be relevant. To maximize effectiveness, education, welfare dependence, smoking, morning sickness, age, and parity are important factors to consider when attempting to change maternal diet during pregnancy. | 18,766,432 |
Bioaccumulation and physiological effects of mercury in Pteris vittata and Nephrolepis exaltata. | Anatomical, histochemical and biochemical approaches were used to study mercury uptake and phytotoxicity as well as anti-oxidative responses in two species of ferns [Chinese brake fern (Pteris vittata) and Boston fern (Nephrolepis exaltata)], grown in a hydroponic system. The roots of both cultivars accumulated large amounts of mercury, but exhibited limited mercury translocation to shoots. Mercury exposure led to more pronounced phytotoxicity accompanied by stronger oxidative stress in the shoots of P. vittata than in N. exaltata. N. exaltata established a more effective anti-oxidative system against mercury-induced oxidative stress than did P. vittata. The activity of anti-oxidative enzymes (superoxide dismutase, catalase and glutathione reductase) increased. The reduced ascorbate (ASA) and oxidized ascorbate (DHA) are regulated. Mercury exposure led to an increase in the concentration of glutathione (GSH) in both fern species. The present study suggests that N. exaltata is more tolerant to mercury exposure than P. vittata, which has been also reported to be more tolerant to arsenic exposure. N. exaltata may thus have potential for phytostabilization of soils or phytofiltration of waste water contaminated with mercury. | 18,766,440 |
Oxidative stress by Helicobacter pylori causes apoptosis through mitochondrial pathway in gastric epithelial cells. | Helicobacter pylori is a gram negative bacterium that infects the human stomach of approximately half of the world's population. It produces oxidative stress, and mitochondria are one of the possible targets and the major intracellular source of free radicals. The present study was aimed at determining mitochondrial alterations in H. pylori-infected gastric epithelial cells and its relationship with oxidative stress, one of the recognized causes of apoptotic processes. Cells were treated with a strain of H. pylori for 24 h. Cellular oxidative burst, antioxidant defense analysis, mitochondrial alterations and apoptosis-related processes were measured. Our data provide evidence on how superoxide acts on mitochondria to initiate apoptotic pathways, with these changes occurring in the presence of mitochondrial depolarization and other morphological and functional changes. Treatment of infected cells with Vitamin E prevented increases in intracellular ROS and mitochondrial damage consistent with H. pylori inducing a mitochondrial ROS mediated programmed cell death pathway. | 18,766,443 |
Infectious exposure in the first year of life and risk of central nervous system tumors in children: analysis of day care, social contact, and overcrowding. | Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case-control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08-1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12-2.83). Those who had attended informal (OR 0.86, 95% CI 0.68-1.09) or formal day care (OR 0.93, 95% CI 0.68-1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation. | 18,766,446 |
Accuracy of retinal changes in predicting microalbuminuria among elderly hypertensive patients: a cross-sectional study from a teaching hospital in South India. | Microalbuminuria is an important marker of end organ damage in hypertensive patients, but is often not tested for, especially in a resource-poor setting. We studied the accuracy of retinal changes in predicting microalbuminuria among a cohort of geriatric hypertensive patients. One hundred and eighty elderly hypertensive patients aged more than 65 years were assessed for their demographic characteristics, smoking status, duration of hypertension, current severity of hypertension, body mass index, left ventricular hypertrophy by electrocardiogram (ECG), and high sensitivity C-reactive protein (HsCRP). Optic fundi were assessed for retinopathy after pupillary dilatation, and were photographed. Microalbuminuria (albumin-creatinine ratio) was measured as an average of two nonconsecutive overnight spot urine samples. Patients with pre-diabetes, diabetes, metabolic syndrome, treatment with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, overt nephropathy or proteinuria, and active infection were excluded. Mean age was 74 +/- 6.56 years. One-third were obese and 18.9% had left ventricular hypertrophy. Prevalence of microalbuminuria was 39.4% and prevalence of retinopathy was 40%. Microalbuminuria showed a strong association with retinopathy (P < 0.0001). Logistic regression identified association of microalbuminuria with duration of hypertension (P = 0.001) and elevated high sensitivity C-reactive protein (P = 0.021). Retinopathy was associated with duration of hypertension (P = 0.001) and smoking (P < 0.0001). Tests of accuracy for retinopathy as a predictor of microalbuminuria showed a sensitivity of 72% and specificity of 81%. Prevalence of microalbuminuria and retinopathy were quite high in our cohort of elderly hypertensive patients. Retinal changes of any grade probably have moderate accuracy in predicting microalbuminuria and hence we can initiate work-up for target organ damage, especially in a resource-poor setting. | 18,766,459 |
CCN2 YAPs at cancer. | The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Previously, it has been shown that CCN2 (connective tissue growth factor, CTGF) is a target of the tumor promoting YAP and its transcription factor target TEAD. A recent report in Genes and Development by Zhao and colleagues (Genes Dev 22:1962-1971 2008) has extended these initial observations to show that CCN2 plays an important role in the growth-promoting function of YAP. These data confirm the role of CCN2 as a key oncogenic mediator. This report briefly summarizes these findings. | 18,766,468 |
Efficacy of avian influenza neuraminidase-specific vaccines in chickens. | This paper investigates the protection induced in chickens by live neuraminidase (N)-specific vaccines against highly pathogenic avian influenza. Vaccination with viruses belonging to N1 and N8 subtypes protected against challenge with virulent viruses of the same N subtype and irrelevant haemagglutinin (H) subtypes. The main advantage of N-specific vaccines is that they do not confuse serological diagnosis by haemagglutination inhibition tests. The anomalous cross-protection between influenza viruses of H1 and H5 subtypes could be exploited to control outbreaks caused by highly pathogenic H5 viruses by using vaccines based on H1 and the appropriate N. | 18,766,509 |
Infectious typhlitis in chickens caused by spirochetes. | A weakly haemolytic spirochete was detected with an unabsorbed fluorescent antiserum to Treponema hyodysenteriae in smears and cultures of scrapings of caecal mucosa of laying hens with diarrhoea. Two groups of experimental chickens were fed a pure culture of this spirochete or homogenated intestinal contents of affected birds. Both groups showed clinical signs of disease such as increased water content of faecal material and slight retardation of growth. A non-specific typhlitis which histologically resembled milder forms of swine dysentery was seen in the birds from which spirochetes were isolated. The isolate obtained differed in cultural, biochemical, anti-genic and morphological characteristics from T. hyodysenteriae. The pathological significance of intestinal spirochetes and their possible epidemiological relation to swine dysentery are discussed. | 18,766,524 |
Pathogenicity of an isolate of Aspergillus flavus in chickens. | Cockerels aged 8 days were each given intraperitoneally a 1 ml suspension of Aspergillus flavus grown on Sabouraud's dextrose agar containing 10(6) colony forming units per ml. No clinical signs were observed but mortality was 37.5%. Liver and kidney were enlarged at necropsy. Granulomatous nodules were found in the serosa and lung parenchyma up to day 16 post-infection but by day 30 post-infection tiny nodules persisted only at the site of inoculation. Periodic acid-Schiff stained sections of the serosa, lung, kidney, liver, spleen and bursa of Fabricius showed the fungus in only the serosa and lungs. There was fibrosis of the hepatic portal canal, congestion and hyperplasia of the bile ducts. In the kidney there was degeneration of mainly the epithelium of proximal convoluted tubules followed by generalised pyknosis. Bursa and spleen showed lymphocytic depletion. The fungus was reisolated from the nodules up to day 16 post-infection. The above observations appear to describe a condition of concurrent mycotoxicosis and aspergillosis due to Aspergillus flavus. | 18,766,525 |
Clinical and pathological changes caused by the interaction of lasalocid and chloramphenicol in broiler chickens. | Uncommon and abnormal gait, characterised by toe walking and progressive leg weakness, was observed in a large broiler flock in Israel. Identical clinical signs were reproduced when young chicks received feed supplemented with lasalocid (Abatec-Roche), and chloramphenicol at normal recommended levels, for 12 days or more. The clinical and pathological findings suggest a neuromuscular toxic effect of lasalocid-chloramphenicol interaction in broiler chicks. To our best knowledge this is the first report on the toxic effect caused by the combination of lasalocid and chloramphenicol. | 18,766,527 |
Pathogenesis of rotavirus infection in turkey poults. | The pathogenesis of rotavirus infection was examined after experimental infection of conventional and specific-pathogen-free (SPF) turkey poults. In six experiments birds were exposed to turkey rotavirus isolates Tu-1 or TU-2 or the chicken isolate Ch-1 at 7, 10 or 42 days of age. Poults were examined between 1 and 24 days post-infection (dpi) for diarrhoea, gross and histopathologic lesions, virus excretion in the intestinal tract, viral antigen in intestinal epithelial cells, and the development of serum antibodies. Between 2 and 5 dpi watery droppings were observed in conjunction with remarkable paleness of the intestinal tract which was grossly observable. Maximum viral replication occurred between 2 and 5 dpi, during which period viral antigen could be demonstrated in the epithelial cells of the duodenum, jejunum, ileum and colon. Sporadically, virus antigen-positive cells were seen in the cecum. As early as 4 to 5 dpi rotavirus antibodies could be detected by indirect immunofluorescence assays. Remarkable leukocyte infiltration of the lamina propria, vacuolation of the epithelial cells and scalloping of the villous surface at the tips were observed in the intestine of infected birds. Infection with rotavirus caused a significant impairment at 2 and 4 dpi of absorption of D-xylose from the intestinal tract. | 18,766,543 |
Demonstration of a Marek's disease virus-specific antigen in tumour lesions of chickens with Marek's disease using monoclonal antibody against a virus phosphorylated protein. | By use of monoclonal antibody against a Marek's disease virus (MDV) serotype 1-specific phosphorylated protein, MDV antigen-positive cells were demonstrated in tumour lesions of various visceral organs of chickens with Marek's disease. However, these tumour lesions did not appear to have the MDV glycoproteins gA and gB, which are considered to be late gene products of the virus genome gA and gB as well as the phosphorylated protein were detected in the feather follicle epithelium, which is a permissive site for MDV replication. | 18,766,550 |
The differential contribution of B and T lymphocytes to susceptibility to Marek's disease in RPL line-7 chickens. | The nature of genetically determined resistance or susceptibility to Marek's disease (MD) has been investigated further in the two histocompatible chicken strains RPL line-6 (resistant) and line-7 (susceptible). Experiments involving the chemical ablation of host bursa cells and reconstitution with bursa cells from the opposing line failed to transfer susceptibility to the acute cytolytic stage of the disease or to lymphoma formation. In contrast, transfer of line-7 thymi into neonatally thymectomised line-6 chickens rendered the recipients susceptible to lymphoma formation, as previously reported. However, a detailed study of the pathogenesis of the disease in these thymus transplant recipients suggested that their enhanced susceptibility was due not to the increased sensitivity of donor lymphocytes to infection with MD virus, but rather to their greater susceptibility to malignant transformation by the virus. | 18,766,557 |
An outbreak of pox among pheasants in Iraq. | Clinical manifestations of pox are described in caged pheasants in Iraq, which killed 28 out of 400 adult pheasants. | 18,766,581 |
Enhancement of natural killer cell activity by Marek's disease vaccines. | Vaccination against Marek's disease with herpesvirus of turkeys (HVT) has been reported to cause increased natural killer (NK) cell activity as detected in vitro against LSCC-RP9 target cells. The effect of vaccination with SB-1 (a nononcogenic chicken herpesvirus), HVT and the HVT/SB-1 combination on NK cell activation was compared in Marek's disease susceptible (P-2) and resistant (N-2) chickens. Birds were vaccinated at 7 days of age and NK cell activity was measured between 3 and 42 days after vaccination. Both SB-1 and HVT caused a significant increase in NK cell-induced specific release. The increase was similar in N-2 and P-2 chickens for either HVT or SB-1, while the combined vaccine induced a significantly higher increase in N-2 compared to P-2 birds. The maximal effect of vaccination on NK cells was detected at 7 days after vaccination. In contrast with the results in young birds, vaccination of birds between 31 and 45 days of age caused either no effect or a suppression rather than an enhancement in NK cell activity. | 18,766,591 |
The effect of increased sodium in the drinking water on right ventricular hypertrophy, right ventricular failure and ascites in broiler chickens. | One hundred commercial male broiler chickens were grown to 27 days in four floor pens on a commercial diet containing 0.14% sodium (Na+). From day 6 each pen received different levels of sodium chloride (NaCl) in the drinking water; 0.0%, 0.15% (0.06% Na+), 0.3% (0.12% Na+) and 0.6% (0.24% Na+). Eight chicks from each group were killed at 13, 20 and 27 days and examined for right ventricular hypertrophy (RVH) and right ventricular failure (RVF). By day 27 as little as 0.06% added Na+ caused two cases of RVH and one case of RVF with ascites, typical of the ascites caused by RVF in commercial broilers. RVH, RVF and ascites developed earlier in broilers on higher levels of Na+. | 18,766,592 |
Development of an enzyme-linked immunosorbent assay for the detection of humoral antibody to Pasteurella anatipestifer. | An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Pasteurella anatipestifer in duck sera is described. As part of the initial assay development, micro-titration plates from different manufacturers were assayed for their suitability to bind P. anatipestifer antigen. The Nunc Immunopiate II was chosen, on account of its overall reproducibility (5.5% coefficient of variation) and the absence of an edge effect. Optimum concentrations of reagents were determined and the inclusion of 1.0M NaCl in the wash buffer was found to reduce non-specific binding and increase assay sensitivity. The assay is specific in that antibodies were detected only in those ducks either exposed to or following vaccination with P. anatipestifer; sera from ducks immunised with other heterologous bacterial antigens, and having agglutinating antibodies to them, gave no detectable response in the ELISA. Between-assay coefficients of variation for the quality control serum pools representing high, medium and low levels of antibodies to P. anatipestifer were 6.8%, 8.3% and 8.6% respectively. A precision-dose profile was derived. A graph of absorbance versus log(2) serum end point titre showed a linear relationship (r = 0.99) over the range investigated. The derived regression line (P<0.001) was used to transform the absorbance measurement obtained for a single 1:100 dilution of serum into a log(2) titre value. It was demonstrated that the ELISA is a much superior method to rapid slide agglutination and agar gel precipitin tests in measuring antibody responses to exposure against P. anatipestifer type 2. | 18,766,597 |
Outbreak of atypical fowlpox in chickens with persistent reticuloendotheliosis viraemia. | During the Autumn in S/Eastern Australia, eight chickens of 7 months of age with an experimentally-induced reticuloendotheliosis virus (REV) viraemia developed cutaneous manifestations similar to fowlpox. Ten hatchmates housed in a separate pen nearby, and known to be free of REV infection, remained clinically normal. Fowlpox virus was isolated from the affected birds and histologically the lesions were characteristic of fowlpox. Unsuccessful application of fowlpox vaccine by wing web 'stab', 2 days after the primary lesions were seen, showed both groups of chickens to have been infected previously by a natural strain of fowlpox virus. The fowlpox virus isolate was found to be virulent for 1-week-old chickens. | 18,766,601 |
Effect of cyclophosphamide on infections produced by Escherichia coli of high and low virulence in chickens. | The effect of cyclophosphamide (Cy) on infections caused by Escherichia coli strains of high (Expt 1) and low (Expt 2) virulence was examined in 4-week-old specified-pathogen-free chickens. In Expt 1 the mortalities of Cy-treated and non-treated chickens given 5 x 10(7) cfu of a strain of E. coli of high virulence were both 100%. In the groups given 5 x 10(5) cfu, the mortality of Cy-treated chickens was 90% and that of non-treated chickens was 10%. In Expt 2 the groups given 1 x 10(9) cfu of an E. coli strain of low virulence showed a mortality of 30% when treated with Cy and 0% when non-treated. The chickens given 5 x 10(7) or 5 x 10(5) cfu showed no mortality, clinical signs or histological lesions. Cy-treated chickens showed severe hypoplasia of granulopoiesis in the bone marrow. Haematological examination of Cy-treated chickens revealed leukopenia, especially lymphopenia, and thrombocytopenia. This study suggests that Cy treatment may enhance infection caused by E. coli strain of high virulence and manifest signs of infection caused by E. coli strain of low virulence in the chickens. | 18,766,611 |
Experimental reproduction of psittacine beak and feather disease/French Moult. | Nestling budgerigars and galahs and one-day-old SPF chickens were inoculated with an homogenate prepared from the feathers of a variety of birds with psittacine beak and feather disease (PBFD), and known to contain virus-like particles 20 nm in diameter. Uninoculated birds were included as in-contact controls and groups of birds were also inoculated with homogenate treated with beta-propriolactone to inactivate any virus present. Typical PBFD developed in many of the inoculated birds and in some in-contact controls but in none of the birds inoculated with inactivated homogenate nor in SPF chickens. It is concluded from these findings that PBFD is an infectious disease of viral aetiology and is identical to the disease in budgerigars commonly referred to as 'French Moult'. | 18,766,613 |
'Cage clutch' in a flock of commercial White Leghorns. | Five commercial White Leghorn chickens were presented to the laboratory from a flock which was experiencing a mortality problem after transfer to the laying house. About 4 or 5% of the birds were 'squatting' in their cages and appeared nervous. Localized, ulcerative lesions were noted on the toes and shanks of the layers. The flock was placed on antibiotics and electrolytes, and the affected birds were removed from their cages and placed on the floor. The problem subsided, and the flock came into production on schedule. Aetiology of the disorder remains unknown. | 18,766,621 |
Production of virus-specific antisera to lymphoproliferative disease virus of turkeys. | Lymphoproliferative disease virus, a recently isolated C-type retro-virus, cannot yet be cultured in cells in vitro and rarely induces a high titre virus-specific antiserum. However, after digestion of purified virus with bromelain and rebanding the treated virus in sucrose gradients bald virions devoid of the viral spike glycoprotein and up to 20 host proteins were found to induce a high level virus-specific antibody response in rabbits and chickens. | 18,766,656 |
Parsley-induced photosensitivity in ostriches and ducks. | Clinical and pathological changes suggesting an acute case of photo-sensitivity were observed in a flock of ostriches. A preliminary diagnosis of parsley (Petroselinum sativum)-induced photosensitisation was confirmed by experimental reproduction of the typical lesions in ducks. This seems to be the first report on natural and experimental induction of photosensitivity in ostriches and ducks caused by the ingestion of parsley. | 18,766,676 |
Efficacy of piperazine dihydrochloride against ascaridia galli in the domestic fowl. | The efficacy of piperazine dihydrochloride (Ascarex D, Rexolin Chemicals AB, Helsingborg, Sweden) was evaluated against natural infections of Ascaridia galli in broiler breeders. The compound was administered in the drinking water at a concentration of 1 or 2%. Efficacy against mature A. galli in controlled anthelmintic tests was 83%, 94% and 100% in birds given 64, 100 and 200 mg/kg body weight of drug respectively. Efficacy against immature worms was 86%, 60% and 100%. In a trial conducted in the field the frequency of fowls which were positive for nematode eggs was reduced from about 50% to 3% following treatment. Egg production in the field trial did not fall and there were no other side-effects associated with use of the drug. | 18,766,706 |
Hatchability and mortality following infection of chick embryos with subgroup a Rous sarcoma virus. | An investigation, using Rhode Island Red, New Hampshire, Columbian and Australorp, was conducted to study the correlation between chorioallantoic membrane (CAM)-infection phenotype to challenge with Bryan strain of Rous sarcoma virus (BS-RSV) of subgroup A and subsequent mortality, following hatching. A total of 806 CAMs and 438 chicks over nine hatch-replicates in three experiments provided evidence that infection via an inoculation of the CAM induced rapid and high mortality, about 72%, averaged over the four breeds, from a fibrosarcomatous liver tumour (LT) in CAM-susceptible chicks. In contrast, only 14% of chicks inoculated via the yolk sac died from liver tumours. Infection via the CAM reduced hatchability by about 28% (P<0.01) as compared to the hatchability of embryos infected via the yolk sac. About 21% of chicks which developed no pocks on the CAM after RSV inoculation developed liver tumours and died. | 18,766,714 |
Natural haemagglutinins and immune responsiveness in young chicks. | Titres of natural haemagglutinins to sheep erythrocytes and of experimentally induced antibodies to Newcastle disease virus (NDV), bovine serum albumin (BSA) and human gammaglobulin (HgG) were determined in White Rock broiler chicks immunised at 28 days of age. There was no relationship between levels of natural haemagglutinins and induced antibody levels or between titres of antibody to NDV and titres of antibody to BSA or HgG. A highly significant correlation (r=0.37) was found between titres of antibody to BSA and to HgG. | 18,766,759 |
Normal and clinical haematology of captive cranes (Gruiformes). | Fall blood counts on 56 clinically normal cranes of nine different species have provided reference values for the interpretation of haematological changes in 13 cranes presenting with abnormal clinical signs. Hypochromic anaemia, heterophilia and lymphocytosis were found in birds with probable Mycobacterium avium infection and heterophilia and lymphocytosis in birds with bumblefoot, arthritis, nephrosis and cardiac myopathy. In several of the cases with heterophilia and lymphocytosis the fibrinogen level was also raised. A senile bird with thickened heart valves showed macrocytosis. The potential diagnostic value of clinical haematology in cranes is discussed. | 18,766,764 |
Acute toxicity of citrinin in turkeys and ducklings. | Citrinin, a naturally occurring mycotoxin, was dissolved in dimethyl-sulphoxide - 70% ethanol (3:1, v/v) and administered orally in two trials to 7-day-old male turkey poults and male white Pekin ducklings. The single dose LD50 value in 7-day-old male turkey poults was 56 mg/kg and in 7-day-old male white Pekin ducklings it was 57 mg/kg. The mycotoxin was nephrotoxic in both species, but the renal lesions were more severe in turkeys and were characterised by degeneration and necrosis of renal tubular epithelium. In turkeys, lesions were found in the liver and included hepatic cell necrosis and biliary hyperplasia. Lymphoid necrosis with depletion involved the thymus and cloacal bursa of turkeys and ducklings. These latter lesions were the most prominent histopathological alterations in citrinin-treated ducklings. | 18,766,779 |
The role of histocompatibility antigens in cell-mediated cytotoxicity against Marek's disease tumour-derived lymphoblastoid cell lines. | The cytotoxic activity of spleen cells from Marek's disease (MD) virus-infected chickens against syngeneic and allogeneic tumour cell lines was compared, using MD lymphoma-derived lymphoblastoid cell lines obtained from two inbred and two outbred chicken strains. Activity was significantly greater against allogeneic than against syngeneic target cells, although some activity against syngeneic cells was detected. Cold target cell inhibition tests confirmed that unlabelled normal spleen cells could block the cytolysis of tumour cell targets bearing the same histocompatibility antigens as the spleen cells. It was concluded that the tumour-specific antigens against which the effector cells were reacting may be modified histocompatibility antigens and that the enhanced cytotoxicity seen with allogeneic target and effector cells may be an artefact analogous to an adjuvant effect. | 18,766,805 |
Mycotoxicoses produced in ducklings and turkeys by dietary and multiple doses of citrinin. | Citrinin was mixed in the diet (100, 250, 500 parts/10(6)) and fed to 1-day-old male White Pekin ducklings (Trial I), or it was dissolved in dimethyl-sulphoxide-70% ethanol (3:1, v/v) and administered by crop gavage to 14-day-old male White Pekin ducklings (Trial II) or 7-day-old male turkey poults (Trial III). Ducklings given 250 or 500 parts/10(6) citrinin diet for 15 days had clinical signs of citrinin toxicity. Body weight gain was significantly decreased by the 500 parts/10(6) diet (P < 0.05). Ducklings fed 250 and 500 parts/10(6) developed nephropathy that was more severe in the 500 parts/10(6) group. The nephropathy was characterised by degeneration, necrosis, mineralisation and regeneration of tubular epithelial cells of both the cortical and medullary regions. Interstitial fibrosis was found in the medullary regions of the 500 parts/10(6) group only and focally was accompanied by interstitial nephritis. Seven daily doses of citrinin equal to a half or three-quarters of the single-dose LD(50) produced no additive toxic effects in either ducklings or turkeys, but body weight gain was significantly decreased in duckling given three-quarters of the single-dose LD(50). | 18,766,819 |
The pathogenicity of some avian reoviruses with particular reference to tenosynovitis. | In two experiments, 13 avian reoviruses from different sources were tested in specific pathogen-free (SPF) light hybrid chicks at 1-day-old for their pathogenicity with particular respect to tenosynovitis. All strains including two from commercial ducks and another from a wedge-tail eagle caused tenosynovitis. In most cases the lesions were macroscopic but in a few only microscopic abnormalities were observed after footpad or oral inoculation. In the first experiment with six British strains, infection by contact also resulted in tenosynovitis, and in most cases virus persisted longer in the hock joint/tendons than in the gut. Among the 13 viruses, two strains, R14 and Lasswade 126/75 were the mildest, producing only slight microscopic lesions of the disease, while strain WVU 2937 was the most virulent for joints/tendons. Five strains caused mortalities when inoculated at high concentration, deaths being due to hepatic necrosis. However, infection at a 1:10 dilution of this dose resulted in tenosynovitis lesions only. None of the strains tested caused signs of stunting or malabsorption syndromes. | 18,766,835 |
Lymphoproliferative disease of turkeys: effect of chemical and surgical bursectomy on viraemia, pathogenesis and on the humoral immune response. | Turkey poults which were surgically or chemically bursectomised after hatching, and inoculated with the lymphoproliferative disease (LPD) virus at 3(1/2) weeks of age, developed typical tumourous lesions in various organs (pancreas, spleen, thymus, liver, gonads and kidneys) to the same extent as intact but inoculated controls. Plasma virus-associated reverse transcriptase activity (as an estimation of viraemia) developed at a higher rate in poults neonatally treated with 16 mg of cyclophosphamide. The chemically bursectomised birds were found to have markedly reduced serum gamma-globulins levels, and low levels or absence of agglutinins to sheep red blood cells and to killed Brucella abortus following immunisation with these antigens. Inoculation of turkey poults with LPD virus did not cause inhibition of the humoral immune response in intact birds but reduced significantly antibody production in surgically bursectomised poults. Since infection with LPD virus was previously shown to cause hypergammaglobulinaemia, and more specifically, a marked increase in serum IgG (7S) levels, it was suggested that the LPD tumour cells might be antibody-producing B-lymphoid cells. However, results presented here indicate that LPD lesions and viraemia can develop even in turkeys lacking any appreciable B-cell activity. | 18,766,844 |
Avian cellular immune effector mechanisms--a review. | Considerable new knowledge has accumulated within the last few years on the immune functions of birds, and data show that the avian cellular immune effector mechanisms are quite similar to those of mammals. Cellular immunity in the chicken, the most widely studied avian species, is primarily mediated by T cells, macrophages and NK cells. The avian T lymphocytes express unique surface antigens that distinguish these cells from other cells. The T cells respond vigorously in vitro to T cell-specific mitogens and can perform cytotoxic and mixed lymphocyte reactions against allogeneic or tumour cell targets. The in vivo responses mediated by T cells include allograft and tumour cell rejection, graft-versus-host reaction and delayed type hypersensitivity reactions. T cells also serve as helper cells in enabling B Cells to produce antibody against thymus-dependent antigens. Avian T cells also perform immune regulatory functions and sub-populations of T suppressor cells can cause profound blockage of antibody production by B cells. Certain T cell functions require cooperation from other immune cells, particularly major histo-compatibility complex-compatible macrophages. Avian macrophages resemble their mammalian counterparts in being adherent and phagocytic, and they serve as accessory cells in a multitude of immune reactions as well as effector cells in their own right. Macrophages when co-cultivated in vitro with tumour target cells may non-specifically arrest proliferation of tumour cells or lyse tumour cells. They may also engage in specific anti-alloantigen cytotoxicity following hyperimmunisation. Under certain circumstances, macrophages can also be potent suppressors of immune reactivity. Birds appear to have a well developed NK cell system. NK cells of chickens share general characteristics with mammalian NK cells and lack the surface markers of T cells, B cells, or macrophages. Recent evidence indicates that the NK cell system plays a role in defence against Marek's disease. NK-like cells have also been shown to mediate ADCC in chickens and ducks. The immunoregulatory factors that may mediate avian immune effector cell functions are currently being actively studied. | 18,766,854 |
Eimeria necatrix: selection and characteristics of a precocious (and attenuated) line. | A line of Eimeria necatrix with an abbreviated life cycle (i.e. a "precocious" line) was derived from the Houghton laboratory strain by repeated passage of the oocysts which were the first to be recovered from infections in chickens. The precocious line had a reproductive potential much lower than that of its parent strain and it was significantly less pathogenic. Its immunogenicity was, however, substantially retained. Selection for precocious development was accompanied by changes in the endogenous development of the parasite with an attendant reduction in its prepatent time. | 18,766,877 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.