title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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[Systemic lupus erythematosus and pregnancy]. | Systemic lupus erythematosus (SLE) is a complex autoimmune disease that predominantly affects women of childbearing age. Prognosis of SLE pregnancy has dramatically improved with the advent in therapeutic management of SLE and in the obstetric care. Consequently, pregnancy is possible in SLE patients when the disease is inactive for at least 6 months. Because of the risk of lupus flare and obstetrical complications (fetal loss, preterm birth, intrauterine growth retardation, preeclampsia), a multidisciplinary approach, associating medical and obstetrical teams, is required. Corticosteroids, hydroxychloroquine and azathioprine are safe in pregnancy and should be kept when necessary. | 18,848,416 |
Oversized acetabular socket causing groin pain after total hip arthroplasty. | The causes of groin pain after total hip arthroplasty are numerous, and the condition itself is disabling. Therefore, it is imperative that the cause of the pain is identified and managed appropriately. We report a case where the patient had groin pain after total hip arthroplasty as a result of an oversized cementless acetabular component, which caused a breach in the anterior wall of the acetabulum. The anterior wall of the acetabulum was reconstructed with femoral head allograft, and the patient has been symptom free since. | 18,848,418 |
Undernutrition in geriatric institutions in South-West France: policies and risk factors. | This study aimed to describe the nutritional status of geriatric home residents according to their place of dwelling and to identify institutional factors associated with higher rates of undernutrition. All institutions (514) in the Aquitaine region were interviewed for staff ratio, nutritional procedures, staff training, and other procedures in the area of nutrition. A stratified random sample of 601 residents in a subsample of 42 institutions underwent Mini-Nutritional Assessment. The estimated prevalence of undernutrition was 19.1 (95% confidence interval [CI] 14.0-24.2), with a higher rate in long-term care (48.0%, 95% CI 15.9-80.2) than in nursing homes (14.5%, 95% CI 10.6-18.4, P < 0.0001). In univariate analyses the risk of undernutrition was higher in long-term care (P < 0.0001), in settings with better weighing equipment (P < 0.0001), with a higher staff ratio (P = 0.0001), and a higher rate of subjects needing help for eating (P < 0.0001) and was lower in settings with a higher rate of training in nutritional screening (P = 0.0001) and management (P < 0.0001). In nursing homes, each item of the Mini-Nutritional Assessment Short Form was independently predictive of undernutrition. In multivariate analyses in nursing homes only, better weighing equipment (adjusted odds ratio 2.34, 95% CI 1.39-4.12, P = 0.0017) and higher staff ratio (adjusted odds ratio 1.03, 95% CI 1.00-1.05, P = 0.0230) were associated with higher rates of undernutrition. Undernutrition in institutions was linked to the resident health problems, with little evidence in favor of the influence of institutional policies. | 18,848,433 |
[Adenocarcinoma of the rectum in a 14-year-old]. | Colorectal cancer is rare in children and adolescents. It is usually associated with predisposing genetic factors, aggressive histology, and poor prognosis. Two familial syndromes are best characterized, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis. They are autosomal dominant inherited disorders. We report the case of a 14-year-old girl having a Dukes D adenocarcinoma of the rectum with peritoneal extension and bone metastases. | 18,848,439 |
The TSC-mTOR signaling pathway regulates the innate inflammatory response. | The innate inflammatory immune response must be tightly controlled to avoid damage to the host. Here, we showed that the tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) pathway regulated inflammatory responses after bacterial stimulation in monocytes, macrophages, and primary dendritic cells. Inhibition of mTOR by rapamycin promoted production of proinflammatory cytokines via the transcription factor NF-kappaB but blocked the release of interleukin-10 via the transcription factor STAT3. Conversely, deletion of TSC2, the key negative regulator of mTOR, diminished NF-kappaB but enhanced STAT3 activity and reversed this proinflammatory cytokine shift. Rapamycin-hyperactivated monocytes displayed a strong T helper 1 (Th1) cell- and Th17 cell-polarizing potency. Inhibition of mTOR in vivo regulated the inflammatory response and protected genetically susceptible mice against lethal Listeria monocytogenes infection. These data identify the TSC2-mTOR pathway as a key regulator of innate immune homeostasis with broad clinical implications for infectious and autoimmune diseases, vaccination, cancer, and transplantation. | 18,848,473 |
Pediatric eye injuries related to consumer products in the United States, 1997-2006. | This study examines which consumer products are most commonly associated with pediatric eye injuries that are treated in emergency departments in the United States. The results demonstrate that, overall, boys experienced proportionally more consumer product-related eye injuries than girls, but eye injuries from specific product categories are more likely to be associated with one sex than the other. Age-specific patterns also revealed that certain product categories are more likely to be associated with eye injuries among different age groups. These findings are salient because children experience a disproportionate amount of ocular trauma, possibly resulting in visual disability or blindness and concomitant developmental delays. Given the heretofore lack of detailed information on products that may contribute to the burden of pediatric eye injuries in the United States, the results of the current study provide valuable information for identifying priorities for prevention and intervention. | 18,848,479 |
Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. | Genomic imprinting regulates parental-specific expression of particular genes and is required for normal mammalian development. How imprinting is established during development is, however, largely unknown. To address this question, we studied the mouse Kcnq1 imprinted cluster at which paternal-specific silencing depends on expression of the noncoding RNA Kcnq1ot1. We show that Kcnq1ot1 is expressed from the zygote stage onward and rapidly associates with chromatin marked by Polycomb group (PcG) proteins and repressive histone modifications, forming a discrete repressive nuclear compartment devoid of RNA polymerase II, a configuration also observed at the Igf2r imprinted cluster. In this compartment, the paternal Kcnq1 cluster exists in a three-dimensionally contracted state. In vivo the PcG proteins Ezh2 and Rnf2 are independently required for genomic contraction and imprinted silencing. We propose that the formation of a parental-specific higher-order chromatin organization renders imprint clusters competent for monoallelic silencing and assign a central role to PcG proteins in this process. | 18,848,501 |
The interaction of biological and noxious transition metals with the zinc probes FluoZin-3 and Newport Green. | Zinc-sensitive fluorescent probes have become increasingly important in the investigation of the cellular roles of zinc. There is, however, little information on how the other transition metals in cells may influence the measurement of zinc. We have characterized in vitro the interaction of the nominal zinc indicators FluoZin-3 and Newport Green with all the cationic transition metals found within cells, Cr, Mn, Fe, Co, and Cu, as well as Ni and Cd, by measuring their dissociation constants. In addition, we have shown how FluoZin-3 can be used to quantify the concentration of copper in a cell-free assay and report that the fluorescence of Newport Green is boosted by both Cu(I) and Fe(II). Furthermore, we have introduced diagnostics for detecting the interference of metals other than zinc with its measurement within cells. | 18,848,515 |
Effects of ceramide and other simple sphingolipids on membrane lateral structure. | The available data concerning the ability of ceramide and other simple sphingolipids to segregate laterally into rigid, gel-like domains in a fluid bilayer has been reviewed. Ceramides give rise to rigid ceramide-enriched domains when their N-acyl chain is longer than C12. The high melting temperature of hydrated ceramides, revealing a tight intermolecular interaction, is probably responsible for their lateral segregation. Ceramides compete with cholesterol for the formation of domains with lipids such as sphingomyelin or saturated phosphatidylcholines; under these conditions displacement of cholesterol by ceramide involves a transition from a liquid-ordered to a gel-like phase in the domains involved. When ceramide is generated in situ by a sphingomyelinase, instead of being premixed with the other lipids, gel-like domain formation occurs as well, although the topology of the domains may not be the same, the enzyme causing clustering of domains that is not detected with premixed ceramide. Ceramide-1-phosphate is not likely to form domains in fluid bilayers, and the same is true of sphingosine and of sphingosine-1-phosphate. However, sphingosine does rigidify pre-existing gel domains in mixed bilayers. | 18,848,519 |
The extracellular domain of luteinizing hormone receptor dictates its efficiency of maturation. | The processing of luteinizing hormone receptor (LHR) shows marked differences in different species. While the human LHR is predominantly expressed as the mature, 90kDa species, rat LHR exists mostly in the 70kDa precursor form. Since the extracellular domain of the LHR is unusually large in comparison with other G protein-coupled receptors, the present studies examined the role of extracellular domain in its processing. FLAG-tagged chimeric LH receptors were constructed by substituting the extracellular domain of the human receptor in rat LHR (hrr) and the extracellular domain of the rat receptor in human LHR (rhh). The intracellular processing, ligand binding and recycling of the chimeric receptors were compared with that of the wild type receptors in 293T cells. The results showed that the human and rat LHR were expressed predominantly as 90 and 70kDa species, respectively, as expected. The introduction of the rat extracellular domain into the human LHR (rhh) decreased the abundance of the mature form with an increase in the precursor form. Conversely, substitution of the extracellular domain of the rat LHR by the extracellular domain of the human LHR (hrr) led to an increase in the mature form with a corresponding decrease in the precursor form. Changes were also observed in the ligand binding and recycling of the wild type and chimeric receptors. These results suggest that the extracellular domain of the LHR is one of the determinants that confer its ability for proper maturation and cell surface expression. | 18,848,524 |
Species and agonist dependent zinc modulation of endogenous and recombinant ATP-gated P2X7 receptors. | Zinc (Zn2+) and copper (Cu2+) are key signalling molecules in the immune system and regulate the activity of many ion channels. Both Zn2+ and Cu2+ potently inhibit rat P2X7 receptors via a binding site identified by mutagenesis. Here we show that extracellular Cu2+ also potently inhibits mouse P2X7 receptors. By contrast, the receptor expression system and agonist strongly influence the action of extracellular Zn2+ at mouse P2X7 receptors. Consistent with previous reports, Zn2+ inhibits recombinant rat P2X7 receptors. However, recombinant mouse P2X7 receptors are potentiated by Zn2+ when activated by ATP4- but inhibited when stimulated with the ATP analogue BzATP4-. Endogenous murine macrophage P2X7 receptors are not modulated by Zn2+ when stimulated by ATP4- however Zn2+ inhibits BzATP4- mediated responses. In summary, these findings provide a fundamental insight into the differential actions of Zn2+ and Cu2+ between different P2X7 receptor species. | 18,848,528 |
Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. | It has been investigated, based on a rat model of human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced alterations in lipid metabolism. For this purpose, the concentrations of free fatty acids (FFA), phospholipids (PL), triglycerides (TG), total cholesterol (TCh), and high and low density lipoprotein cholesterol (HDL and LDL, respectively) as well as the concentrations of chosen indices of lipid peroxidation such as lipid peroxides (LPO), F2-isoprostane (F2-IsoP) and oxidized LDL (oxLDL) were estimated in the serum of male Wistar rats administered Cd (5 or 50mg/l) or/and Zn (30 or 60mg/l) in drinking water for 6 months. The exposure to 5 and 50mg Cd/l resulted in marked alterations in the lipid status reflected in increased concentrations of FFA, TCh, LDL, LPO, F2-IsoP and oxLDL, and decreased concentrations of PL and HDL in the serum. The concentrations of LDL, LPO, F2-IsoP and oxLDL were more markedly enhanced at the higher Cd dosage. The supplementation with Zn during the exposure to 5 and 50mg Cd/l entirely prevented all the Cd-induced changes in the serum concentrations of the estimated lipid compounds and indices of lipid peroxidation, except for the F2-IsoP for which Zn provided only partial protection. Based on the results it can be concluded that Zn supplementation during exposure to Cd may have a protective effect on lipid metabolism consisting in its ability to prevent hyperlipidemia, including especially hypercholesterolemia, and to protect from lipid peroxidation. The findings seem to suggest that enhanced dietary Zn intake during Cd exposure, via preventing alterations in the body status of lipids may, at least partly, protect against some effects of Cd toxicity, including oxidative damage to the cellular membranes and atherogenic action. The paper is the first report suggesting protective impact of Zn against proatherogenic Cd action on experimental model of chronic moderate and relatively high human exposure to this toxic metal. | 18,848,534 |
Effects of alpha-tocopherol (vitamin E) on the stability and lipid dynamics of model membranes mimicking the lipid composition of plant chloroplast membranes. | Tocopherol (vitamin E) is widely recognized as a cellular antioxidant. It is essential for human and animal health, but only synthesized in photosynthetic organisms, where it is localized in chloroplast membranes. While many studies have investigated non-antioxidative effects of tocopherol on phospholipid membranes, nothing is known about its effects on membranes containing chloroplast glycolipids. Here, liposomes resembling plant chloroplast membranes were used to investigate the effects of alpha-tocopherol on vesicle stability during freezing and on lipid dynamics. alpha-Tocopherol had a pronounced influence on membrane dynamics and showed strong interactions in its effects on membrane stability during freezing with the cryoprotectant sucrose. alpha-Tocopherol showed maximal effects at low concentrations (around 2mol%), close to its contents in chloroplast membranes. | 18,848,546 |
Behavioral phenotypes persist after gonadal steroid manipulation in white-throated sparrows. | White-throated sparrows (Zonotrichia albicollis) exhibit a behavioral polymorphism that segregates with a plumage marker. Individuals with a white stripe (WS) on the crown engage in an aggressive strategy that involves more singing, whereas individuals with a tan stripe (TS) sing less and engage in more parental care. Previous work has shown that plasma levels of gonadal steroids differ between the morphs in both sexes, suggesting a hormonal mechanism for the polymorphic behavior in this species. Here, we eliminated morph differences in plasma levels of testosterone (T) in males and estradiol (E2) in females in order to test whether morph differences in behavior would be similarly eliminated. Males and females in non-breeding condition were treated with T or E2, respectively, so that plasma levels in the treated groups were high and equal between the WS and TS morphs. We found that despite hormone treatment, WS and TS birds differed with respect to singing behavior. WS males sang more in response to song playback than did TS males, and WS females exhibited more spontaneous song than TS females. We also found that WS males gave more chip calls, which are often used in contexts of territorial aggression. Overall, these results suggest that WS birds engage in more territorial vocalization, particularly song, than do TS birds, even when T or E2 levels are experimentally equalized. This behavioral difference may therefore be driven by other factors, such as steroid metabolism, receptor expression or function, or steroid-independent neurotransmitter systems. | 18,848,562 |
Homodimeric chicken galectin CG-1B (C-14): Crystal structure and detection of unique redox-dependent shape changes involving inter- and intrasubunit disulfide bridges by gel filtration, ultracentrifugation, site-directed mutagenesis, and peptide mass fingerprinting. | Intrafamily gene diversification has led to three prototype galectins in chicken [i.e., chicken galectin (CG)-1A, CG-1B, and CG-2] that show distinct expression profiles and developmental regulation. In order to pinpoint structural disparities among them, we determined the crystal structure of CG-1B. Alteration of the position of the Trp ring in the lectin site and the presence of only two ordered water molecules therein, as well as changes in the interface region between the two subunits, set the structure of CG-1B clearly apart from that of CG-1A. Intriguingly, the unique presence of two Cys residues at positions 2 and 7 in the N-terminal region translated into formation of an intersubunit disulfide bridge between the Cys7 residues of the homodimer in the crystal. In solution, oxidation is associated with significant shape changes in the dimeric protein and the additional occurrence of a compacted form with an intrasubunit disulfide bridge between Cys2 and Cys7. The single-site mutant C7S/C7V was not subjected to such changes, supporting the crucial role of Cys7 in redox-dependent shape changes. These results point to the functional significance of the distinctive presence of the two Cys residues in the N-terminal region of CG-1B. | 18,848,566 |
The high-resolution NMR structure of the early folding intermediate of the Thermus thermophilus ribonuclease H. | Elucidation of the high-resolution structures of folding intermediates is a necessary but difficult step toward the ultimate understanding of the mechanism of protein folding. Here, using hydrogen-exchange-directed protein engineering, we populated the folding intermediate of the Thermus thermophilus ribonuclease H, which forms before the rate-limiting transition state, by removing the unfolded regions of the intermediate, including an alpha-helix and two beta-strands (51 folded residues). Using multidimensional NMR, we solved the structure of this intermediate mimic to an atomic resolution (backbone rmsd, 0.51 A). It has a native-like backbone topology and shows some local deviations from the native structure, revealing that the structure of the folded region of an early folding intermediate can be as well defined as the native structure. The topological parameters calculated from the structures of the intermediate mimic and the native state predict that the intermediate should fold on a millisecond time scale or less and form much faster than the native state. Other factors that may lead to the slow folding of the native state and the accumulation of the intermediate before the rate-limiting transition state are also discussed. | 18,848,567 |
Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner. | It has been recently proposed that pro-inflammatory genes such as cyclooxygenase-2 (COX-2) play a key role in the aging process. However, it remains unclear whether the pro-inflammatory activity of COX-2 is involved in the aging process and whether COX-2 inhibitors prevent aging. We therefore examined the effect of COX-2 inhibitors on aging in the cellular senescence model of human dermal fibroblasts (HDFs). While the catalytic activity of COX-2 was observed to increase in the senescence process, we found that among three selective COX-2 inhibitors studied, only NS-398 inhibited the senescence whereas celecoxib and nimesulide accelerated the senescence. Non-selective COX inhibitors including aspirin, ibuprofen and flurbiprofen accelerated the senescence. The senescence-regulating effect of selective COX-2 inhibitors had no correlation with cellular reactive oxygen species levels, NF-kappaB activities or protein levels of p53 and p21. We instead found that selective COX-2 inhibitors regulate caveolin-1 expression at transcriptional levels, which was closely associated with the inhibitors' effect on the senescence. Collectively, these results suggest that COX-2 catalytic activity does not mediate HDF senescence and that selective COX-2 inhibitors modulate HDF senescence by a catalytic activity-independent mechanism. | 18,848,576 |
Real-time RT-PCR (TaqMan) assays for the detection of viruses associated with Rugose wood complex of grapevine. | Real-time TaqMan RT-PCR (TaqMan RT-PCR) assays were developed to detect the viruses associated with Rugose wood complex of grapevines. The viruses detected were Rupestris stem pitting-associated virus in the genus Foveavirus, Grapevine virus A, Grapevine virus B and Grapevine virus D in the genus Vitivirus. The coat protein was found to be the most conserved gene within the viral species, therefore, the primers and probes for TaqMan RT-PCR assays were designed from the multiple alignment of the coat protein sequence of various isolates of each virus. Comparisons were also made between the conventional one step RT-PCR and TaqMan RT-PCR for the detection of these viruses using four-fold serial dilutions of both purified RNA and crude extract prepared from grapevine tissue. Results showed that TaqMan RT-PCR was more sensitive and could detect viruses at 32- and 256-fold higher dilutions for purified RNA and crude extract, respectively, compared to RT-PCR. The use of an internal control (18S rRNA) allowed comparison of sample preparation protocols and amplification efficiencies between samples. | 18,848,580 |
Identification of outer membrane proteins with emulsifying activity by prediction of beta-barrel regions. | Microbial bioemulsifiers are secreted by many bacteria and are important for bacterial interactions with hydrophobic substrates or nutrients and for a variety of biotechnological applications. We have recently shown that the OmpA protein in several members of the Acinetobacter family has emulsifying properties. These properties of OmpA depend on the amino acid composition of four putative extra-membrane loops, which in various strains of Acinetobacter, but not in E. coli, are highly hydrophobic. As many Acinetobacter strains can utilize hydrophobic carbon sources, such as oil, the emulsifying activity of their OmpA may be important for the utilization and uptake of hydrocarbons. We assumed that if outer membrane proteins with emulsifying activity are physiologically important, they may exist in additional oil degrading bacteria. In order to identify such proteins, it was necessary to obtain bioinformatics-based predictions for hydrophobic extra-membrane loops. Here we describe a method for using protein sequence data for predicting the hydrophobic properties of the extra-membrane loops of outer membrane proteins. The feasibility of this method is demonstrated by its use to identify a new microbial bioemulsifier - OprG - an outer membrane protein of the oil degrading Pseudomonas putida KT2440. | 18,848,588 |
Vaccination coverage and awareness of infectious risks in patients with an absent or dysfunctional spleen in the Netherlands. | To evaluate the current practice to prevent infections in patients with an absent or dysfunctional spleen in a part of the Netherlands. To measure serum antibody levels against Streptococcus pneumoniae and Haemophilus influenzae type b. Observational study of vaccination coverage by analysis of questionnaires and serum antibody levels. Primary care practices in the Utrecht area of the Netherlands, catchment area 750,000 inhabitants, period 2006-2007. One hundred and thirty adult patients with an absent or dysfunctional spleen. Percentage of patients informed about infectious risks and aware of the timely use of antimicrobial prophylaxis. Vaccine coverage against S. pneumoniae, H. influenzae type b and Neisseria meningitidis. Levels of serum antibodies against S. pneumoniae and H. influenzae type b. Fifty-six patients (43%) have not received up-to-date information about the infectious risks associated with their condition; 65 patients (50%) are not aware of the need to contact a physician immediately in case of high fever; 37 patients (28%) are keeping antimicrobial prophylaxis at home. Pneumococcal vaccination has been administered within the last 5 years to 103 of 130 patients, antibody levels above the threshold of > or =0.35microg/mL are found in 83 of the 101 patients (data lacking in 2 patients). Complete coverage against S. pneumoniae is only 64% (83/130). A minority of patients (respectively 32% and 27%) has been vaccinated against H. influenzae type b and N. meningitidis. Vaccination coverage and education about infectious risks in patients with an absent or dysfunctional spleen can be improved markedly in the Netherlands. | 18,848,594 |
Arsenic accumulation, elimination, and interaction with copper, zinc and manganese in liver and kidney of rats. | The arsenic accumulation, distribution and influences on metallothionein-1 (MT-1) expression and other trace elements in various organs were examined in rats orally exposed to sodium arsenate (iAs(V)). Rats received a dose of 0, 1, 10 and 100ppm of iAs(V) in drinking water daily for 4- and 16-weeks. Arsenic seems to be distributed in all of the tissues, and was accumulated relatively higher in the spleen, lung and kidney compared to the liver, and much lower in skin and cerebrum. High dose of iAs(V)-exposure significantly increased the concentration of copper in the kidney, but did not influence other trace elements such as zinc and manganese in the liver. The mRNA expression of MT-1 was dose-dependently increased by iAs(V)-exposure in the liver whereas it was decreased in the kidney. These data indicate that arsenic is widely distributed and significantly accumulated in various organs and influences on other trace elements, and also modulates MT-1 expression in the liver and kidney. | 18,848,598 |
Effects of velocity and motion-onset delay on detection and discrimination of sound motion. | The effect of velocity on auditory motion processing in combination with a motion-onset delay was investigated in two experiments. The detection of motion onset and discrimination of motion direction were studied, employing a psychophysical reaction time task. Listeners were presented with sounds moving along the frontal horizontal plane in a dark anechoic environment. Response times (RTs) were measured, while the velocity (20 degrees /s, 40 degrees /s, 80 degrees /s) and the motion-onset delay (the time between sound onset and start of motion: 0, 200, 500, 1000 ms) were varied. Listeners responded faster with higher velocity and longer motion-onset delay. In particular, with higher velocity, the function relating RT to motion-onset delay had a steeper initial decrease than with lower velocities. The results are in line with psychophysical studies of the minimum audible movement angle and recent electrophysiological data about the role of motion velocity in auditory motion processing. The effect of motion-onset delay is discussed with regard to a dynamic temporal window, in which auditory spatial information is integrated until enough information is accumulated to trigger motion detection. | 18,848,613 |
Effects of cisplatin and other Pt(II) complexes on spontaneous motility of isolated human oviduct. | The toxicity of platinum(II) ion could be significantly modified by coordination with some organic compounds. In our study, the cytotoxicity and the influence of platinum(II) complexes, such as cisplatin, cis-[PtCl(2)(NH(3))(2)], [PtCl(2)(SMC)] and [PtCl(2)(DMSO)(2)] (where SMC is S-methyl-l-cysteine and DMSO is dimethyl sulphoxide) on spontaneous motility of isolated human fallopian tubes were investigated. Cisplatin showed potent pro-apoptotic effects on peripheral blood mononuclear cells (PBMC). However, peripheral blood mononuclear cells were substantially less sensitive to [PtCl(2)(SMC)] and [PtCl(2)(DMSO)], and these compounds showed no toxic effect on PBMC in all concentrations examined. Cisplatin showed concentration-dependent inhibition of spontaneous contractions of the isolated ampulla. (EC(50)=1.14+/-0.03 x 10(-6)M/l, r=0.714, p<0.05) while [PtCl(2)(SMC)] and [PtCl(2)(DMSO)(2)] did not affect spontaneous contractions of isolated fallopian tube ampulla. | 18,848,615 |
Quality of regulatory elements in Drosophila retrogenes. | Retrogenes are processed copies of genes that are inserted into new genomic regions and that acquire new regulatory elements from the sequences in their surroundings. Here we use a comparative approach of phylogenetic footprinting and a non-comparative approach of measuring motif over-representation in retrogenes in order to describe putative elements present in cis-regulatory regions of 94 retrogenes recently described in Drosophila. The detailed examination of the motifs found in the core promoter regions of retrogenes reveals an abundance of the DNA replication-related element (DRE), the Initiator (Inr), and a new over-represented motif that we call the GCT motif. Parental genes also show an abundance of DRE and Inr motifs, but these do not seem to have been carried over with retrogenes. In particular, we also examined motifs upstream of retrogenes expressed in adult testis and were able to identify 6 additional over-represented motifs. Comparative analyses provide data on the conservation and origin of some of these motifs and reveal 15 additional conserved motifs in these retrogenes. Some of those conserved motifs are sequences bound by known transcription factors, while others are novel motifs. In this report we provide the first genome-wide data on which specific cis-regulatory regions can be recruited by retrogenes after they are inserted into new coding regions in the genome. Future experiments are needed to determine the function and role of the new elements presented here. | 18,848,618 |
Determinants of the NF-kappaB response to acute psychosocial stress in humans. | Previous research has shown that psychosocial stress is associated with an increased activity of the transcription factor nuclear factor-kappaB (NF-kappaB), a major inducer of inflammatory genes. While considerable individual variation has been noted, factors contributing to this variation have not been described so far. Therefore, 29 healthy participants (35.8+/-12 yrs) were exposed to the Trier Social Stress Test. Blood was collected before and repeatedly afterward for determination of NF-kappaB activity, leukocyte subset numbers, cortisol, norepinephrine, and in vitro-stimulated IL-6 production. Additionally, age, sex, and ratings of perceived chronic and acute stress were assessed. Regression analyses revealed that older participants showed a lower NF-kappaB stress response compared to younger adults (beta= -.42, p=.026). Higher NF-kappaB stress responses were associated with lower cortisol stress responses (beta= -.37, p=.05), higher pre-stress IL-6 production (beta=.38, p=.043), and high chronic in combination with low acute stress, or vice versa (beta= -.61, p=.06). Norepinephrine and sex were not associated with NF-kappaB stress responses (all p.13). In summary, the present study shows for the first time in human psychosocial stress the negative association of cortisol and NF-kappaB. This parallels results from in vitro studies. Our finding of lower NF-kappaB stress responses in older age and in people with high chronic and acute stress might be interpreted as an adaptive dampening of NF-kappaB activity. In the absence of longitudinal data, however, this interpretation remains speculative. | 18,848,620 |
Issues with threshold masking in voxel-based morphometry of atrophied brains. | There is great interest in using automatic computational neuroanatomy tools to study ageing and neurodegenerative disease. Voxel-based morphometry (VBM) is one of the most widely used of such techniques. VBM performs voxel-wise statistical analysis of smoothed spatially normalised segmented Magnetic Resonance Images. There are several reasons why the analysis should include only voxels within a certain mask. We show that one of the most commonly used strategies for defining this mask runs a major risk of excluding from the analysis precisely those voxels where the subjects' brains were most vulnerable to atrophy. We investigate the issues related to mask construction, and recommend the use of alternative strategies which greatly decrease this danger of false negatives. | 18,848,632 |
Mitochondrial DNA damage and its potential role in retinal degeneration. | Mitochondria are central to retinal cell function and survival. There is increasing evidence to support an association between mitochondrial dysfunction and a number of retinal pathologies including age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. The past decade has highlighted mitochondrial genomic instability as an important factor in mitochondrial impairment culminating in age-related changes and age-related pathology. This represents a combination of the susceptibility of mitochondrial DNA (mtDNA) to oxidative damage and a limited base excision repair pathway. This random cumulative mtDNA damage leads to cellular heteroplasmy and, if the damage affects a sufficient proportion of mitochondria within a given cell, results in loss of cell function and greater susceptibility to stress. mtDNA damage is increased in the neural retina and RPE with ageing and appears to be greatest in AMD. It thus appears that the mitochondrial genome is a weak link in the antioxidant defenses of retinal cells and that deficits in mitochondrial DNA (mtDNA) repair pathways are important contributors to the pathogenesis of retinal degeneration. Specifically targeting mitochondria with pharmacological agents able to protect against oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of retinal degenerations such as AMD. | 18,848,639 |
The targeted delivery of cancer drugs across the blood-brain barrier: chemical modifications of drugs or drug-nanoparticles? | One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood-brain barrier (BBB) using transvascular routes following intravenous administration. The development of BBB targeting technologies is a very active field of research and development. One goal is to develop chemically modified derivatives of drugs or chemically modified nanoparticulate vectors of drugs, capable of crossing biological barriers, in particular the BBB. This manuscript will review the approaches that have been explored to achieve these goals, using chemical functionalization of drugs or of drug vector systems and endogenous transporters at the BBB. | 18,848,640 |
Therapeutic potential of type A (I) lantibiotics, a group of cationic peptide antibiotics. | Type A (I) lantibiotics are cationic antimicrobial peptides that have a potential usefulness in treating infectious diseases. They are known to have a potent and broad spectrum of activity, an insignificant cytotoxicity, and demonstrated efficacy in animal infection models, suggesting therapeutic potential. In this review, topics pertaining to their basic structure, mode of bactericidal activity, pharmacology, and methods of manufacture are described. | 18,848,642 |
Variations in admission practices for adolescents with anorexia nervosa: a North American sample. | The purpose of this study was to assess the variability in admission practices and medical inpatient care for adolescent patients with anorexia nervosa (AN). Participants consisted of members of the 2001-2003 Eating Disorder Special Interest Group from the Society for Adolescent Medicine who completed a structured telephone interview about their admission practices and patterns of inpatient care for teens with AN. Questions focused on admission threshold for heart rate (HR), percentage of ideal body weight (% IBW), and refeeding protocols. Case vignettes were used. Of 95 eligible practitioners, 51 (53%) agreed to participate. Participants represented 25 American states, one Canadian province, and 45 different adolescent programs. The majority of physicians reported they would hospitalize an AN patient with HR <40 beats/min. The most common response for when to hospitalize based on % IBW was 75% IBW. There were no differences in admission practices based on number of years in practice, gender of physician, or practice setting. Regional differences in admission practices were noted, with physicians in the western United States less likely to admit patients with HR >or=40 beats per minute (p = .018). Physicians described 28 different methods of advancing a diet during an admission. Only 37% of physicians were aware of a standardized refeeding protocol in their institution. This study indicates variability in admission criteria and refeeding practices and shows evidence of geographic variations of admission standards. These data provide a baseline for outcome trials investigating medical admissions for adolescents with AN. | 18,848,669 |
Cardiovascular abnormalities in Turner's syndrome: what prevention? | Cardiovascular complications in Turner's syndrome are the most common cause of excess early mortality, with a life expectancy that may be reduced by more than 10 years. Congenital cardiac abnormalities are described in approximately one third of patients. These abnormalities are mostly left heart obstructions, the most common of which are bicuspid aortic valve (16%) and coarctation of the aorta (11%). Dilatations of the ascending aorta are often described and may occur in isolation from any heart disease, suggesting a vasculopathy specific to the syndrome, probably predisposed to by extracardiac risk factors such as oestrogen deficiency, diabetes, dysplidaemia and overweight. The most feared complication is aortic dissection with around a 100 cases, described at average age of approximately 35-years-old. This is believed to complicate 2% of induced pregnancies. Hypertension (HBP) usually essential, affects up to 50% of patients with Turner's syndrome. This is an important risk factor for cardiovascular complications and justifies aggressive treatment. On the other hand, retrospective studies have not demonstrated adverse cardiological effects due to growth hormone treatments. Patients with Turner's syndrome merit regular cardiology follow-up from childhood onwards, particularly if they have treated heart disease. The merits of preventative treatments for aortic dilatation have not been demonstrated in Turner's syndrome and justify prospective trials. | 18,848,691 |
Fluorescent isotope-coded affinity tag (FCAT). I: Design and synthesis. | A novel class of isotope-coded affinity tag is proposed possessing a fluorescent feature, referred to as fluorescent isotope-coded affinity tag (FCAT), to provide a new tool for quantitative proteomics. The label is designed to bind cysteine containing proteins or peptides. The FCAT reagent comprises four functional elements: a specific chemical reactivity group toward sulfhydryl groups; a linker that can incorporate the stable isotopes; a hydroxymethylbenzoic residue (base labile group) to cleave off a large part of the label before MS analysis; and a fluorescent tag for absolute quantification. The fluorescent part of the tag is also planned to be utilized to isolate the FCAT-labeled peptides via antibody based pull-down method. In this paper, we report on the solid phase organic synthesis of the light isotope containing FCAT molecule. The new labeling reagent showed good reactivity with model cysteine containing peptides. The fluorophore group was also effectively cleaved off from the labeled products to accommodate easier MS based analysis. | 18,848,712 |
The Asthma Control and Communication Instrument: a clinical tool developed for ethnically diverse populations. | Lower levels of quality asthma care among racially diverse populations might be due to inaccurate disease status assessments. The Asthma Control and Communication Instrument (ACCI) is a new tool that captures patient report of disease status during routine care. We sought to test the ACCI's psychometric properties in a racially diverse population. We performed a cross-sectional study. Subjects were recruited from specialist and generalist urban outpatient clinics. The ACCI and measures of asthma control, quality of life, lung function, and specialist rating of asthma status were collected. Four ACCI domains were separately validated: Acute Care, Bother, Control, and Direction. Principal component analysis, internal consistency, concurrent, discriminative, known-groups validity, and accuracy were evaluated. Two hundred seventy asthmatic patients (77% female subjects, 55% black) participated. ACCI Control domain internal consistency was 0.80. ACCI Bother, Control, and Direction domains showed strong concurrent validity with asthma control and quality-of-life measures (all P < .001). ACCI Acute Care and Direction domains showed strong concurrent validity with individual validation items (all P < .001). The ACCI Control domain discriminated clinically important levels of disease status measured by asthma control, quality of life (both P < .001), and percent predicted peak expiratory flow rate (P = .005) and was associated with specialist rating of disease status (P < .001), confirming known-groups validity. The accuracy of the ACCI Control domain in classifying patients with uncontrolled asthma was very good (area under the curve, 0.851; 95% CI, 0.742-0.95870). Results were similar for both black and white subjects. The ACCI is a promising clinical tool that measures asthma disease status during routine health care and is valid for use in both black and white populations. | 18,848,721 |
Multi-morphological biodegradable PLGE nanoparticles and their drug release behavior. | A series of amphiphilic tri-block copolymers based on poly(lactide-co-glycolide)-b-poly(ethylene oxide)-b-poly(lactide-co-glycolide) (PLGE) with various segment ratios of PEO/PLGA and segment lengths of PEO were synthesized. Multi-morphological biodegradable nanoparticles - PLGE-NPs were fabricated by an improved emulsion/solvent evaporation technique in the absence of surfactant. By adjusting segment ratio of PLGA/PEO (w/w) and molecular weight of PEO, various morphological and nanoscale sized spheres, elliptic spheres, short rods and threads could be formed. The auto-assembling mechanism of the PLGE-NPs and influencing effectors of composition of the PLGE on morphology of the PLGE-NPs were discussed. The PLGE-NPs were biodegradable, and the factors that affected the degradation rate of the PLGE-NPs were also discussed. By using the amphiphilic PLGE polymer, the biodegradable nanoscale immunosuppressive agent - multi-morphological Cyclosporine (CsA)-loaded PLGE-NPs was fabricated. CsA release behavior of the CsA-loaded PLGE-NPs in vitro was determined, and the effect factors on CsA release behavior of the CsA-loaded PLGE-NPs were discussed. | 18,848,724 |
The interaction of native calf thymus DNA with Fe(III)-dipyrido[3,2-a:2',3'-c]phenazine. | The mono and bis dipyrido[3,2-a:2',3'-c]phenazine (dppz) adducts of iron(III) chloride, i.e. [Fe(dppz)]Cl(3) and [Fe(dppz)(2)]Cl(3), have been synthesized and characterized. The interaction of the Fe(III)dppz hydrolyzed aquo complex with native calf thymus DNA has been monitored as a function of the metal complex-DNA molar ratio, by variable temperature UV absorption spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. The results obtained in solution at various ionic strength values give support for a tight intercalative binding of the Fe(III)dppz cation with DNA. In particular, the appearance of induced CD bands, caused by the addition of Fe(III)dppz, indicate the existence of a rigid metal complex-DNA-binding leading to dominating chiral organization of Fe(III)dppz species within the DNA double helix. The trend of selected CD bands with the molar concentration of Fe(III)dppz emphasizes that the presence of high amounts of metal complex induces also the formation of DNA-Fe(III)dppz supramolecular aggregates in solution. The analysis of fluorescence measurements allowed us to calculate a value of the intercalative binding constant comparable to that obtained by UV spectrophotometric titration. Finally, the temperature dependence of the absorbance at 258nm shows that the metal complex strongly increases the DNA melting temperature already at metal complex-DNA molar ratio equal to 0.25 suggesting that metal complex intercalation effectively hinders DNA denaturation. Overall, the results of the present study point out that the Fe(III)dppz aquo complex has DNA-binding properties analogous to those previously reported for the tris-chelate Fe(II)(phen)(2)dppz complex (phen=1,10-phenantroline). | 18,848,728 |
Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region. | Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from non-hospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa(-mecI). When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa(-mecI) were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments. | 18,848,735 |
Integrating co-morbid depression and chronic physical disease management: identifying and resolving failures in self-regulation. | Research suggests that treatments for depression among individuals with chronic physical disease do not improve disease outcomes significantly, and chronic disease management programs do not necessarily improve mood. For individuals experiencing co-morbid depression and chronic physical disease, demands on the self-regulation system are compounded, leading to a rapid depletion of self-regulatory resources. Because disease and depression management are not integrated, patients lack the understanding needed to prioritize self-regulatory goals in a way that makes disease and depression management synergistic. A framework in which the management of co-morbidity is considered alongside the management of either condition alone offers benefits to researchers and practitioners and may help improve clinical outcomes. | 18,848,740 |
Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus. | In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito-temporo-parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter. | 18,848,752 |
Selective medical treatment of infected aneurysms of the aorta in high risk patients. | Infected aneurysm of the aorta is almost always fatal without undergoing aortic resection. Medical treatment was attempted selectively in patients who were considered too high risk for surgery. We review our experience with 22 patients treated without undergoing aortic resection over 12 years. Retrospective chart review. Between 1995 and 2007, 22 cases of infected aortic aneurysms treated without undergoing aortic resection during the first admission were included. There were 17 men with a median age of 76 years (range, 35 to 88 years). Of 18 pathogens isolated, the most common responsible microorganism was nontyphoid Salmonella in 11 followed by Staphylococcus aureus in five. The site of infection was thoracic in eight and abdominal in 14. The hospital mortality rate was 50%, and the aneurysm-related mortality rate after long-term follow-up was 59%. The event-free survival rate at one year was 32%. Of 11 patients with Salmonella infection, eight patients have lived beyond 30 days and six were event-free after one year. Of 11 patients with non-Salmonella, four patients have lived beyond 30 days and only one was event-free after one year. The overall aneurysm-related mortality rate was 36% in Salmonella infected patients and 82% in non-Salmonella infected patients. Clinical results of medical treatment using current antibiotics in patients with infected aortic aneurysm were poor. Traditional surgical excision of infected aortic aneurysms with revascularization remains the gold standard and should be attempted except in high risk patients. | 18,848,757 |
Characterising vancomycin's immunotoxic profile using Swiss and CFW mice as an experimental model. | Immunotoxicology can lead to determining the adverse effects of different compounds on the immune system. Sometimes, many drugs (especially antibiotics) induce immune alterations, mainly auto-immunity. This study was aimed at determining vancomycin's immunotoxic effect by comparing the original molecule to two of the most used copies. Thirty-two mice from two murine strains (Swiss and CFW) were treated with three antibiotic formulations for studying its effect on splenic lymphoid and peripheral blood cell populations by using haemograms, flow cytometry and blastogenesis assays. The results indicated that vancomycin produces neutropenia and lymphocytosis in peripheral populations and that it induces a selective immunomodulatory effect on splenocyte sub-populations, depending on formulation and the strain so treated. | 18,848,766 |
Soluble TNFR II/IgG1 Fc fusion protein treatment in the LPS-mediated septic shock of rats. | Tumor necrosis factor-alpha (TNF-alpha) is thought to play a major role in systemic inflammation associated with sepsis. A potent TNF antagonist, a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (sTNFR II/IgG1 Fc fusion protein, sTNFR:Fc), has been shown to provide rapid and sustained improvement in local inflammation diseases by binding TNF-alpha and preventing its proinflammatory activities. To explore the potential therapeutic efficacy for septic shock of sTNFR:Fc, we investigate the effect of this molecule on the survival rate, blood pressure, serum TNF-alpha bioactivity as well as the expression of TNF-alpha at mRNA level in the liver in a LPS-induced rat septic shock model. Blood pressure of the rats was monitored by multi-channel creature signal analysis system. Serum TNF-alpha level and bioactivity was assessed using an enzyme-linked immunoassay and a L929 cytotoxicity assay, respectively. The expression of TNF-alpha mRNA in liver was examined by semi-quantitative RT-PCR. sTNFR:Fc administered to rats 24h before LPS challenge ablated the rise in serum TNF-alpha bioactivity that occurs in response to LPS and protected against hypotension and death. These results indicate that TNF-alpha is a mediator of fatal septic shock, and suggest that sTNFR:Fc offer a potential therapy of systemic infection. | 18,848,768 |
Composition and production rate of solid waste from dental laboratories in Xanthi, Greece. | The composition and production rate of solid waste produced by four dental laboratories were measured in the Prefecture of Xanthi (Greece) during 2002. The selected dental labs in Xanthi were expected to produce approximately 75% of the waste produced from of all seven dental laboratories in the Xanthi Prefecture. Sampling was performed during a 2-month period. Solid waste was categorized into three major categories: (a) infectious and potentially infectious waste, (b) non-infectious toxic waste and (c) household type solid waste. Dental laboratories solid waste (DLSW) was produced at a rate of 0.059 g/cap/day (or 22 g/cap/year) at the time of the study. Household type waste, infectious and potentially infectious waste and non-infectious toxic waste comprised approximately 74%, 26% and less than 0.5% of the total DLSW weight produced, respectively. DLSW was estimated to be approximately 0.007% of the amount of municipal solid waste produced in the Prefecture of Xanthi. | 18,848,772 |
Recycling of waste glass as a partial replacement for fine aggregate in concrete. | Waste glass creates serious environmental problems, mainly due to the inconsistency of waste glass streams. With increasing environmental pressure to reduce solid waste and to recycle as much as possible, the concrete industry has adopted a number of methods to achieve this goal. The properties of concretes containing waste glass as fine aggregate were investigated in this study. The strength properties and ASR expansion were analyzed in terms of waste glass content. An overall quantity of 80 kg of crushed waste glass was used as a partial replacement for sand at 10%, 15%, and 20% with 900 kg of concrete mixes. The results proved 80% pozzolanic strength activity given by waste glass after 28 days. The flexural strength and compressive strength of specimens with 20% waste glass content were 10.99% and 4.23%, respectively, higher than those of the control specimen at 28 days. The mortar bar tests demonstrated that the finely crushed waste glass helped reduce expansion by 66% as compared with the control mix. | 18,848,773 |
Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors. | Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors. | 18,848,780 |
A genetic contribution to circulating cytokines and obesity in children. | Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children. | 18,848,781 |
Management of Stage II testicular seminoma over a period of 40 years. | To review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy. A retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed. A total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19-71). Median follow-up was 21 years (range: 1.2-42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up. In Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma. | 18,848,787 |
Ultrasound-promoted synthesis of novel dispirocyclic frameworks from aza-Claisen rearrangements of Baylis-Hillman amines. | A novel tetracyclic frameworks of dispiropyrrolizidines can be obtained in moderate to good yields via the 1,3-dipolar cycloaddition of azomethine ylides with dipolarophiles derived from aza-Claisen rearrangement of Baylis-Hillman amines. The transformations are highly regioselective and stereoselective, affording the desired compounds in reduced time and increased yields under ultrasound irradiation at room temperature. All the products are confirmed by 1H, 13C NMR, IR and MS spectra, while their molecular structures are elucidated by X-ray crystallography of a selected sample. | 18,848,799 |
Management of post-partum hemorrhage in low-income countries. | The provision of safe and effective delivery care for all women in poor countries remains elusive, resulting in a continuing burden of mortality in general and mortality from post-partum haemorrhage in particular. Deployment of a functional health system and effective linkage of the health system to communities are the necessary prerequisites for the provision of the life-saving technical interventions that will make a difference in individual cases. Sadly, two factors militate against progress: the mantra that 'we know what works' (resulting in some serious gaps in evidence for best practice in resource-poor settings) and a lack of large-scale investment in maternity services to counteract the degradation of infrastructure and depletion of human resources evident in many countries. | 18,848,808 |
Digital image referral for suspected skin malignancy--a pilot study of 300 patients. | Referral of suspect skin cancers as well as non malignant symptomatic skin lesions using high quality digital images transferred via a secure electronic referral system (ERS) potentially offers significant advantages regarding speed of referral, diagnosis and subsequent treatment over conventional pathways. However concerns over safety of the diagnostic process have been raised. This prospective study looks at 300 patients referred by ERS. A comparison of the diagnoses made from digital images with the diagnoses confirmed on pathology reports for lesions excised is described using a random selection of patients' images and referrals. Intra observer analysis of was also assessed. A sample group of patients with lesions deemed as benign, not requiring surgery or other treatment and therefore not seen in secondary care were revisited at a special clinic to determine the safety of the referral system. In this series of 300 patients the study concludes that digital image referral for skin malignancy and other cutaneous lesions reduced the interval between referral and diagnosis by 81% and referral to commencement of treatment in suspect lesions by 30%. Diagnostic accuracy in a random sample of 30 patients was comparable to that reported for patients seen in face to face consultations. High levels of GP and patient satisfaction were recorded. In conclusion digital image referral for skin malignancy and other cutaneous lesions is a safe and cost effective referral pathway, significantly reducing the interval between referral diagnosis and onset of treatment for skin malignancy. | 18,848,815 |
Bovine serum amine oxidase and spm potentiate docetaxel and interferon-alpha effects in inducing apoptosis on human cancer cells through the generation of oxidative stress. | It was previously demonstrated that bovine serum amine-oxidase (BSAO) and SPM (SPM) addition to cancer cells induces cell growth inhibition and over-run the multi-drug resistance (MDR) phenotype through the oxidative stress caused by polyamine metabolites. In this study, it is reported that BSAO/SPM enzymatic system antagonizes the survival pathway induced by either docetaxel (DTX) or interferon alpha (IFNalpha) in human epidermoid cancer KB cells. The combination of BSAO/SPM with either DTX or IFNalpha had a synergistic effect on cell growth inhibition through apoptosis in both human epidermoid KB and breast cancer MCF-7 cell lines. The effects of the BSAO/SPM-DTX combination on apoptosis were caspase 3 and 9-dependent and were paralleled by the enhancement of intracellular O(2-), nitric oxide levels and of lipo-oxidation. The scavenger moiety N-acetyl-cysteine antagonized the effects on apoptosis and cell growth inhibition induced by the combination suggesting a role of the oxidative products of SPM. These effects occurred together with a decrease of the physiological scavenger MnSOD and an increase of both p38 kinase activity and DNA damage. The results suggest that DTX and IFNalpha could sensitize tumour cells to the oxidative stress and apoptosis induced by BSAO/SPM through the induction of a survival ras-dependent pathway and the consequent elevation of the intracellular polyamine pool. These data allow the design of new therapeutic strategy based on the use of this combination in human neoplasms. | 18,848,847 |
Post-apoptotic tumors are more palatable to dendritic cells and enhance their antigen cross-presentation activity. | Critical issues for cytotoxic lymphocyte (CTL) cross-priming are (a) the maturation state of dendritic cells (DC), (b) the source of the tumor-associated antigens (TAA) and (c) the context in which they are delivered to DCs. Drug-induced apoptosis has recently been implicated in CTL cross-priming. However, since drug-treatment produces in vivo more tumor cells than the DC default apoptotic clearance program can cope with, they are expected to proceed to secondary necrosis and change their molecular pattern. Here we have addressed this issue on renal carcinoma cells (RCC) by using different apoptotic stimuli. UVC, but not gamma-irradiation or anthracyclins, induced after 4h treatment of the RCC cell line K1 a combination of apoptotic (phosphatydilserine and calreticulin plasma membrane mobilization) and necrotic (membrane incompetence) features. Heat shock protein (Hsp)-70 and chromatin-bound high mobility box 1 HMGB1 protein, typical of necrosis, were released during the further 20h and thus made accessible to co-cultured monocyte-derived immature (i) DC. UVC-treated, secondary necrotic RCC cell lines were cross-presented with higher efficiency by cytokine-matured (m) DC than their early apoptotic (i.e. gamma-irradiated) counterpart. Upstream events such as increased tumor uptake, activation of genes involved in the antigen-processing machinery, and increased expression of costimulatory and maturation molecules were also observed after loading iDC with secondary necrotic, but not apoptotic, tumor cells. These data offer a description of the molecular and immunogenic characteristics of post-apoptotic tumors which can be exploited to increase the efficiency of in vivo and ex vivo TAA delivery to the DC cross-presentation pathway. | 18,848,858 |
Fin-mutant female zebrafish (Danio rerio) exhibit differences in association preferences for male fin length. | Females often choose to associate with males that have exaggerated traits. In fishes, this may reflect an overall preference for larger size in a potential mate. Female zebrafish (Danio rerio) prefer males with larger bodies but not longer fins. The availability of mutant and transgenic strains of zebrafish make this a unique model system in which to study the role of phenotypic variation in social and sexual behavior. We used mutant strains of zebrafish with truncated (short fin) and exaggerated (long fin) fins to further examine female preferences for fin length in dichotomous association tests. Wild type females showed no preferences between wild type males and short fin mutant males or between wild type males and long fin mutant males. short fin females also showed no preference for short fin males or wild type males while long fin females preferred to associate with long fin males over wild type males. These results suggest that the single gene long fin mutation that results in altered fin morphological may also be involved in a related female association preference. | 18,848,866 |
The toxic effects of microcystin-LR on the reproductive system of male rats in vivo and in vitro. | The aim of this study was to investigate whether microcystin-LR, one of the most common cyanobacterial toxins has toxic effects on reproductive system in vivo or Leydig cells in vitro. Male rats were treated with MC-LR (i.p.) at a dose of 0, 5, 10 or15 microg/(kgday) for 28 days. Leydig cells were cultured with a culture medium including 0, 0.5, 5, 50 or 500 nM MC-LR. In vivo study, we observed exposure to 5 microg/(kgday) of MC-LR decreased the sperm motility, increasing the sperm abnormality rate, 15 microg/(kgday) of MC-LR led to the decrease of testis weight and sperm concentration, decreased the levels of serum testosterone, FSH and LH. The histological findings showed that the seminiferous tubules atrophied and obstructed. In vitro study evaluated MC-LR-induced toxicity and oxidative stress in Leydig cells. It was observed 50 and 500 nM MC-LR significantly decreased the cell viability, increasing the apoptotic DNA fragmentation, and increasing the ratio of necrotic cells. The Leydig cells exposed to MC-LR decreased testosterone production. 500 nM MC-LR increased ROS production, 50 or 500 nM MC-LR enhanced the lipid peroxidation. All Leydig cells exposed to MC-LR showed decreased SOD activity. The results of this study showed that the oxidative stress of MC-LR might lead to cytotoxicity, which may play an important role in cell apoptosis. Then could reduce the production of testosterone in Leydig cells and result in reproductive toxicity. | 18,848,877 |
Molecular evolution of the cadherin superfamily. | This review deals with the large and pleiotropic superfamily of cadherins and its molecular evolution. We compiled literature data and an in-depth phylogenetic analysis of more than 350 members of this superfamily from about 30 species, covering several but not all representative branches within metazoan evolution. We analyzed the sequence homology between either ectodomains or cytoplasmic domains, and we reviewed protein structural data and genomic architecture. Cadherins and cadherin-related molecules are defined by having an ectodomain in which at least two consecutive calcium-binding cadherin repeats are present. There are usually 5 or 6 domains, but in some cases as many as 34. Additional protein modules in the ectodomains point at adaptive evolution. Despite the occurrence of several conserved motifs in subsets of cytoplasmic domains, these domains are even more diverse than ectodomains and most likely have evolved separately from the ectodomains. By fine tuning molecular classifications, we reduced the number of solitary superfamily members. We propose a cadherin major branch, subdivided in two families and 8 subfamilies, and a cadherin-related major branch, subdivided in four families and 11 subfamilies. Accordingly, we propose a more appropriate nomenclature. Although still fragmentary, our insight into the molecular evolution of these remarkable proteins is steadily growing. Consequently, we can start to propose testable hypotheses for structure-function relationships with impact on our models of molecular evolution. An emerging concept is that the ever evolving diversity of cadherin structures is serving dual and important functions: specific cell adhesion and intricate cell signaling. | 18,848,899 |
Inflammatory bowel disease in African American children compared with other racial/ethnic groups in a multicenter registry. | Few epidemiologic investigations characterize inflammatory bowel disease (IBD) in non-Caucasian children. Our study compared IBD characteristics between African Americans and non-African Americans enrolled in a multicenter pediatric IBD registry with endoscopic- and pathology-based diagnosis. The study retrieved data entered from January 2000 to October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community US pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African Americans and non-African Americans in the following categories: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6 y, 6-12 y, or >12 y) at diagnosis or symptom onset; presence of extraintestinal manifestations, Z-scores for height and weight, immunomodulatory therapy, anatomic disease location, and abnormal hemoglobin, albumin, or sedimentation rate at diagnosis. A total of 1406 patients had complete data, 138 (10%) of whom were African American. African Americans more often were older than 12 years of age at diagnosis (52% vs 37%; odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.28-2.59) and symptom onset (46% vs 30%; OR, 1.99; 95% CI, 1.40-2.84); had Crohn's disease (78% vs 59%; OR, 2.36; 95% CI, 1.56-3.58); and had a low hemoglobin level at diagnosis (39% vs 17%; OR, 3.15; 95% CI, 1.92-5.17). IBD in African American children and adolescents presents more commonly with Crohn's disease and at older ages compared with non-African Americans. Racial/ethnic differences in the epidemiology of IBD, particularly Crohn's disease, among American youths require further investigation. | 18,848,910 |
Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells. | Conditioned medium (CM) from clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with differing invasive abilities, were examined for their effect on in vitro invasion. Conditioned medium from Clone #3 (CM#3) strongly promoted invasion, while CM from Clone #8 (CM#8) inhibited invasion in vitro. 2D DIGE followed by MALDI-TOF MS analysis of CM#3 and CM#8 identified 41 proteins which were differentially regulated; 27 proteins were down-regulated and 14 proteins up-regulated in the invasion-promoting CM#3 when compared to CM#8. Western blotting analysis confirmed the down-regulated expression of gelsolin and the up-regulation of aldehyde dehydrogenase 1A1 in CM#3. Down-regulation of aldehyde dehydrogenase 1A1 in Clone #3 CM and gelsolin levels in Clone #8 CM by siRNA transfection revealed an important involvement of these proteins in promoting and inhibiting invasion in these pancreatic cancer cell lines. | 18,848,913 |
Pretreatment with near-infrared light via light-emitting diode provides added benefit against rotenone- and MPP+-induced neurotoxicity. | Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to nigrostriatal degeneration. The inhibition of mitochondrial respiratory chain complex I and oxidative stress-induced damage have been implicated in the pathogenesis of PD. The present study used these specific mitochondrial complex I inhibitors (rotenone and 1-methyl-4-phenylpyridinium or MPP(+)) on striatal and cortical neurons in culture. The goal was to test our hypothesis that pretreatment with near-infrared light (NIR) via light-emitting diode (LED) had a greater beneficial effect on primary neurons grown in media with rotenone or MPP(+) than those with or without LED treatment during exposure to poisons. Striatal and visual cortical neurons from newborn rats were cultured in a media with or without 200 nM of rotenone or 250 microM of MPP(+) for 48 h. They were treated with NIR-LED twice a day before, during, and both before and during the exposure to the poison. Results indicate that pretreatment with NIR-LED significantly suppressed rotenone- or MPP(+)-induced apoptosis in both striatal and cortical neurons (P<0.001), and that pretreatment plus LED treatment during neurotoxin exposure was significantly better than LED treatment alone during exposure to neurotoxins. In addition, MPP(+) induced a decrease in neuronal ATP levels (to 48% of control level) that was reversed significantly to 70% of control by NIR-LED pretreatment. These data suggest that LED pretreatment is an effective adjunct preventative therapy in rescuing neurons from neurotoxins linked to PD. | 18,848,925 |
3-Methoxytyramine, an extraneuronal dopamine metabolite plays a physiological role in the brain as an inhibitory regulator of catecholaminergic activity. | 3-Methoxytyramine (3-MT), an extraneuronal metabolite of dopamine, present in the synaptic cleft at a very low amount (low nanomolar range), comparable to dopamine concentration, is generally regarded as a biologically inactive compound. We have shown in this study that 3-MT binds to the rat noradrenergic cortical alpha(1) and striatal dopamine D(1) and D(2) receptors in nanomolar concentration range, and to cortical alpha(2) adrenoceptor at low micromolar concentration. Bilateral intrastriatal injections of 3-MT (0.25 micromol in 0.5 microl) did not affect significantly locomotor activity in naive rats but strongly antagonized amphetamine-induced (1 mg/kg s.c.) hypermotility. Biochemical studies in rat brain structures showed that 3-MT behaved as an antagonist of the noradrenergic system, i.e. accelerated noradrenaline metabolism and counteracted the inhibitory effect of amphetamine on the rate of noradrenaline metabolism. In contrast to a general view about the lack of physiological role of monoamine metabolites, these results for the first time strongly suggest that an extraneuronal metabolite of dopamine, 3-MT plays an important physiological role as an inhibitory regulator counteracting excessive stimulation of catecholaminergic neurons in the striatum. | 18,848,930 |
A mouse model of Clostridium difficile-associated disease. | Infection with Clostridium difficile causes nosocomial antibiotic-associated diarrhea and colitis. Hamsters historically have been used to investigate disease pathogenesis and treatment, but are not ideal models because of the lack of hamster-specific reagents and genetically modified animals, and because they develop fulminant disease. The aim of this study was to establish a mouse model of antibiotic-induced C. difficile-associated disease (CDAD) that more closely resembles human disease. C57BL/6 mice were exposed to a mixture of antibiotics (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 3 days. Two days later, they were given injections of clindamycin and then challenged 1 day later with different doses of C. difficile. Mice that were exposed to antibiotics and then challenged with C. difficile developed diarrhea and lost weight. Disease severity varied from fulminant to minimal in accordance with the challenge dose. Typical histologic features of CDAD were evident. Oral vancomycin prevented CDAD in all mice, but 68% died from colitis after treatment was discontinued. All animals that survived an initial episode of CDAD showed no evidence of diarrhea or colitis after subsequent rechallenge with C. difficile. Different strains of C. difficile tested in the model showed different levels of virulence in mice. We have developed a mouse model of CDAD that closely represents the human disease. In light of the recent substantial increases in CDAD incidence and severity, this model will be valuable in testing new treatments, examining disease pathogenesis, and elucidating mechanisms of protective immunity. | 18,848,941 |
Transient expression of a polydnaviral gene, CpBV15beta, induces immune and developmental alterations of the diamondback moth, Plutella xylostella. | The diamondback moth, Plutella xylostella, parasitized by its endoparasitoid wasp, Cotesia plutellae, undergoes various physiological alterations which include immunosuppression and an extended larval development. Its symbiotic virus, C. plutellae bracovirus (CpBV), is essential for their successful parasitization with more than 136 putative genes encoded in the viral genome. CpBV15beta, a CpBV gene, has been known to play significant role in altering host physiological processes including hemocyte-spreading behavior through inhibition of protein synthesis under in vitro conditions. In the current study, we investigated its specific involvement in physiological processes of the host by transient expression and RNA interference techniques. The open reading frame of CpBV15beta was cloned into a eukaryotic expression vector and this recombinant CpBV15beta was transfected into nonparasitized 3rd instar P. xylostella by microinjection. CpBV15beta was expressed as early as 24h and was consistent up to 72h. Due to the expression of this gene, plasma protein levels were significantly reduced and the ability of the hemocytes to adhere and spread on extracellular matrix was inhibited, wherein CpBV15beta was detectable in the cytoplasm of hemocytes based on an indirect immunofluorescence assay. To confirm the role of CpBV15beta, its double stranded RNA could efficiently recover the hemocyte-spreading behavior and synthesis of plasma proteins suppressed by the transient expression of CpBV15beta. In addition, the larvae transfected with CpBV15beta significantly suffered poor adult development probably due to lack of storage proteins. Thus these results demonstrate the role of CpBV15beta in altering the host physiological processes involving cellular immune response and metamorphic development, which are usually induced by wasp parasitization. | 18,848,950 |
Neuromuscular electrical stimulation of the hindlimb muscles for movement therapy in a rodent model. | Neuromuscular electrical stimulation (NMES) can provide functional movements in people after central nervous system injury. The neuroplastic effects of long-term NMES-induced repetitive limb movement are not well understood. A rodent model of neurotrauma in which NMES can be implemented may be effective for such investigations. We present a rodent model for NMES of the flexor and extensor muscles of the hip, knee, and ankle hindlimb muscles. Custom fabricated intramuscular stimulating electrodes for rodents were implanted near identified motor points of targeted muscles in ten adult, female Long Evans rats. The effects of altering NMES pulse stimulation parameters were characterized using strength duration curves, isometric joint torque recruitment curves and joint angle measures. The data indicate that short pulse widths have the advantage of producing graded torque recruitment curves when current is used as the control parameter. A stimulus frequency of 75 Hz or more produces fused contractions. The data demonstrate ability to accurately implant the electrodes and obtain selective, graded, repeatable, strong muscle contractions. Knee and ankle angular excursions comparable to those obtained in normal treadmill walking in the same rodent species can be obtained by stimulating the target muscles. Joint torques (normalized to body weight) obtained were larger than those reported in the literature for small tailed therian mammals and for peak isometric ankle plantarflexion in a different rodent species. This model system could be used for investigations of NMES assisted hindlimb movement therapy. | 18,848,960 |
The chicken as a natural model for extraintestinal infections caused by avian pathogenic Escherichia coli (APEC). | E. coli infections in avian species have become an economic threat to the poultry industry worldwide. Several factors have been associated with the virulence of E. coli in avian hosts, but no specific virulence gene has been identified as being entirely responsible for the pathogenicity of avian pathogenic E. coli (APEC). Needless to say, the chicken would serve as the best model organism for unravelling the pathogenic mechanisms of APEC, an extraintestinal pathogen. Five-week-old white leghorn SPF chickens were infected intra-tracheally with a well characterized APEC field strain IMT5155 (O2:K1:H5) using different doses corresponding to the respective models of infection established, that is, the lung colonization model allowing re-isolation of bacteria only from the lung but not from other internal organs, and the systemic infection model. These two models represent the crucial steps in the pathogenesis of APEC infections, including the colonization of the lung epithelium and the spread of bacteria throughout the bloodstream. The read-out system includes a clinical score, pathomorphological changes and bacterial load determination. The lung colonization model has been established and described for the first time in this study, in addition to a comprehensive account of a systemic infection model which enables the study of severe extraintestinal pathogenic E. coli (ExPEC) infections. These in vivo models enable the application of various molecular approaches to study host-pathogen interactions more closely. The most important application of such genetic manipulation techniques is the identification of genes required for extraintestinal virulence, as well as host genes involved in immunity in vivo. The knowledge obtained from these studies serves the dual purpose of shedding light on the nature of virulence itself, as well as providing a route for rational attenuation of the pathogen for vaccine construction, a measure by which extraintestinal infections, including those caused by APEC, could eventually be controlled and prevented in the field. | 18,848,980 |
Sociodemographic and behavioral predictors of bed time and wake time among US adolescents aged 15 to 17 years. | To examine bed times and wake times in US adolescents aged 15 to 17 years using time diaries to determine whether adolescent sleep has changed in recent years and what factors determine bed times and wake times. Time diary analysis using 2 national probability samples: 1981 Time Use Longitudinal Panel Study (n = 130) and 2003-2006 American Time Use Survey (n = 2978). Average time in bed on school days was about 8 hours and was 1 to 2 hours longer on non-school days. Bed times and wake times were similar in 1981 and 2003-2006. Sociodemographic factors and daytime activities, specifically computer use and social activities, predicted bed time. On school days, school start time was the strongest predictor of wake time. Every hour earlier that school started, wake time was about 25 minutes earlier. Adolescents spent less than the recommended 9 hours in bed on school days. There is no evidence that this is a recent change in bed times and wake times, however. Although many factors influence bed time, school start time is the strongest determinant of wake time on school days. Increased computer use and earlier school days may be contributing to insufficient sleep in adolescents. | 18,849,051 |
Effects of temporary calf removal and eCG on pregnancy rates to timed-insemination in progesterone-treated postpartum Nellore cows. | The objective was to evaluate the effects of temporary calf removal (TCR), eCG administration, or both, in a progesterone-based protocol. Suckled Nellore cows (40-80 d postpartum, n=443) with body condition scores from 2.0 to 3.5 (5-point scale) on three farms were all given a synchronizing protocol (PEPE). At the start (designated Day 0), cows were given an intravaginal device (1.0 g of progesterone) and 2.5mg of estradiol benzoate (EB) im. On Day 8, the device was removed and cows were given PGF(2 alpha) (150 microg of D-cloprostenol im), followed in 24h by 1.0mg EB im, and 30-36 h thereafter, fixed-time AI. The design was a 2 x 2 factorial; main effects were TCR (54-60 h; from device removal to FTAI) and eCG treatment (300 IU im, concurrent with PGF(2 alpha)). Transrectal ultrasonography was done on Days -10 and 0 to detect anestrus (absence of a CL at both examinations) and approximately 30 d after FTAI (pregnancy diagnosis). Data were analyzed by logistic regression. The following variables did not significantly affect pregnancy rates: farm, postpartum interval, cyclicity, inseminators, and semen (sire). Overall, 77% of the cows were deemed anestrus. Pregnancy rates were similar (P>0.05) among treatment groups: Control (54/108=50.0%), TCR (44/106=41.5%), eCG (63/116=54.3%), and TCR+eCG (49/113=43.4%). Pregnancy rate was higher in multiparous than primiparous cows (186/360, 51.7% vs. 24/83, 28.9%, P<0.01), but was not significantly affected by cyclicity status or body condition score. In conclusion, temporary calf removal, eCG, or both, did not significantly increase pregnancy rate to timed-insemination in a progesterone-based synchronization protocol in postpartum Nellore cows with acceptable body condition. | 18,849,065 |
Planktonic and benthic microalgal community composition as indicators of terrestrial influence on a fringing reef in Ishigaki Island, Southwest Japan. | Microalgal-based indicators were used to assess terrestrial influence on Shiraho coral reef of Ishigaki Island (Okinawa, Japan). A typhoon occurred on 4-5 August 2005 and sampling were made on three occasions thereafter (6, 8, and 11 August). Pre-typhoon sampling was conducted on 26 July. The typhoon-enhanced terrestrial discharges increased reef nutrient levels (e.g. average NO(3)(-)-N: 0.088mg/L pre-typhoon to 0.817mg/L post-typhoon). This elevated chlorophyll-a concentrations by four times and shifted phytoplankton composition (spectral class-based) from an initial dominance of diatoms and green microalgae to the dominance of bluegreen microalgae (cyanobacteria) and cryptophytes. Cyanobacteria later increased by more than 200% and accounted for as much as 80% of total chl-a ( approximately 0.29microg/L), possibly assisted by favorable nutrient availability. In outer reef waters, diatoms and green microalgae predominated whereas cyanobacteria and cryptophytes were nearly undetectable. Due to detrital decomposition and river discharge, the CDOM was much higher in the inner reef than in the outer reef. Benthic bluegreen microalgae were relatively more abundant in areas close to the river mouth and coastal agricultural fields. At these locations, nutrient concentrations were much higher due to river discharge and potentially significant groundwater discharge. Thus, phytoplankton and benthic microalgae can serve as indicators of terrestrial influence on coral reefs. | 18,849,068 |
Evaluation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) conduits for peripheral nerve regeneration. | Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was investigated for possible application in repairing damaged nerves. Porous nerve conduits with both uniform wall porosity and non-uniform wall porosity were prepared using a particle leaching method. Adult Sprague-Dawley (SD) rats weighing 200-250 g were used as the animal model. The conduits were employed to bridge the 10mm defects in the sciatic nerve of the Sprague-Dawley (SD) rats. Mechanical tests showed that the PHBHHx nerve conduits had proper mechanical properties including maximal loads of 3.1N and 1.3N for the conduits with non-uniform wall porosity and with uniform wall porosity, respectively, and maximal stresses of 2.3 MPa and 0.94 MPa for the conduits with non-uniform wall porosity and with uniform wall porosity, respectively. At the same time, both types of conduits were permeable to three compounds tested including glucose, lysozyme and bovine serum albumin, indicating the suitability of the conduits for free exchanges of nutrients. Compound Muscle Action Potentials (CMAPs) were clearly observed in both types of the PHBHHx nerve conduits after 1 month of implantation, indicating a rapid functional recovery for the disrupted nerves. The results of histological sections demonstrated that the internal sides of the conduits with non-uniform wall porosity were compact enough to prevent the connective tissues from ingrowth penetration. After implantation for 3 months in the rats, the conduits with uniform wall porosity and those with non-uniform wall porosity lost 24% and 20% of their original weight average molecular weights, respectively. Combined with the strong mechanical properties, good nerve regeneration ability and non-toxicity of its degradation products, PHBHHx nerve conduits can be developed into a useful material to repair nerve damage. | 18,849,069 |
Zap-70 positive chronic lymphocytic leukemia co-existing with Jak 2 V671F positive essential thrombocythemia: a common defective stem cell? | Essential thrombocythemia (ET) co-existing with chronic lymphocytic leukemia (CLL) is extremely rare. We report two cases of ET with Jak 2 V617F in Zap-70+ CLL. ET is a myeloproliferative stem cell disease. Zap-70 expression in CLL correlates with non-mutated immunoglobulin genes. The occurrence of a less mature CLL in patients with a pluripotential stem cell disease raises the possibility that an initial "trigger hit" occurred in a pre-Jak 2 common early progenitor in these patients. Subsequent additional molecular events accumulated independently following myeloid and lymphoid differentiation, leading to the development of two diseases of likely identical origin but different lineages. | 18,849,073 |
Schizotypal traits and cognitive function in healthy adults. | Growing evidence has shown that psychometrically identified schizotypes among student populations have subtle cognitive impairments in several domains such as attention, working memory and executive function, but the possible association between psychometric schizotypy in adult populations and cognitive function has not been well documented. Here we examined the association between schizotypal traits as assessed by the Schizotypal Personality Questionnaire (SPQ) and cognitive function including memory, attention, executive function, and general intelligence in 124 healthy adults. Cognitive functioning was assessed with the Wechsler Memory Scale-Revised (WMS-R), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Wisconsin Card Sorting Test (WCST). SPQ scores showed a significant inverse correlation with verbal IQ and the information, comprehension and similarities subtests. No correlation was found between SPQ scores and memory, attention, performance IQ, or executive functioning. These results indicate that schizotypal traits in healthy adults are associated with verbal IQ decrements, suggesting that schizotypal traits themselves, even at a non-clinical level, may play unfavorable roles in cognitive functioning, which is in line with the viewpoint that schizotypy is on a continuum with normality, with its extreme form being clinically expressed as schizophrenia. | 18,849,081 |
Myelination progression in language-correlated regions in brain of normal children determined by quantitative MRI assessment. | To investigate the myelination progression course in language-correlated regions of children with normal brain development by quantitative magnetic resonance imaging (MRI) analysis compared with histological studies. The subjects were 241 neurologically intact neonates, infants and young children (128 boys and 113 girls) who underwent MRI between 2001 and 2007 at the University of Tokyo Hospital, ranging in age from 0 to 429 weeks corrected by postnatal age. To compare their data with adult values, 25 adolescents and adults (14 men and 11 women, aged from 14 to 83 years) were examined as controls. Axial T2-weighted images were obtained using spin-echo sequences at 1.5 T. Subjects with a history of prematurity, birth asphyxia, low Apgar score, seizures, active systemic disease, congenital anomaly, delayed development, infarcts, hemorrhages, brain lesions, or central nervous system malformation were excluded from the analysis. Seven regions of interest in language-correlated areas, namely Broca's area, Wernicke's area, the arcuate fasciculus, and the angular gyrus, as well as their right hemisphere homologous regions, and the auditory cortex, the motor cortex, and the visual cortex were examined. Signal intensity obtained by a region-of-interest methodology progresses from hyper- to hypointensity during myelination. We chose the inferior cerebellar peduncle as the internal standard of maturation. Myelination in all these seven language-correlated regions examined in this study shared the same curve pattern: no myelination was observed at birth, it reached maturation at about 1.5 years of age, and it continued to progress slowly thereafter into adult life. On the basis of scatter plot results, we put these areas into three groups: Group A, which included the motor cortex, the auditory cortex, and the visual cortex, myelinated faster than Group B, which included Broca's area, Wernicke's area, and the angular gyrus before 1.5 years old; Group C, consisting of the arcuate fasciculus, has similar degree of myelination as Group B before 1.5 years but then myelinated more slowly after 3 years of age. No gender or left-right differences between homologous regions were found. In this study, we determined the sequence of myelination of language-correlated regions in infants and children by quantitative MRI assessment. The higher cortical areas matured later than the primary cortical areas, and the arcuate fasciculus matured last. The observation that myelination reaches maturity after 18 months suggests that myelination may be a reason for the acceleration in vocabulary acquisition observed in children from that age. The slow pace of myelination also suggested the possibility of language development's continuation into early adult life. Myelination assessed by MRI was at least 1 month behind that assessed by histological staining. No gender or left-right hemisphere differences in myelination were noted. | 18,849,083 |
The extraordinary healing properties of the pediatric tympanic membrane: a study of atelectasis in the pediatric ear. | Traumatic perforations of the eardrum are generally treated conservatively as they tend to heal spontaneously. Retraction pockets of the eardrum, leading to atelectasis of the middle ear and often ultimately though unpredictably, to cholesteatoma formation, are treated in a variety of ways including complex grafting procedures. On the premise that a surgically resected retraction pocket is in essence a traumatic perforation, we examined the results of spontaneous healing of the resected retraction pocket. Retrospective case note study. A group of 86 ears in 62 patients who had undergone simple excision of the atrophic segment of the eardrum and who had no grafting procedure of the resultant defect, were followed at 6 days, 6-7 weeks and then every 6 months to determine the incidence of spontaneous healing of the eardrum. Audiograms were taken preoperatively, at 7 weeks and between 7 and 15 months postoperative. 94.2% of the eardrums (81 out of 86 ears) healed spontaneously without any form of grafting within 7 weeks. Air bone gap showed improvement in 53 patients. Only one of the four ears that failed to achieve closure had postoperative ear discharge. There were no other complications. In 17 ears (19.8%) there was a recurrence of the atelectasis. Excision of retraction pockets in pediatric ear atelectasis, in principle does not require grafting, as the great majority will heal spontaneously. The spontaneous healing in this study is comparable to reported studies of spontaneous healing of traumatic perforations. Irrespective of the size of the atrophic part of the membrane, recurrence rates for the atelectasis after simple excision is similar to that described in other studies. Retraction pockets may be excised and allowed to heal without risk to the hearing. | 18,849,084 |
Fine vs. coarse complete all-in-one admixture infusions over 96 hours in rats: fat globule size and hepatic function. | The United States Pharmacopeia (USP) has adopted Chapter <729> that set two globule size limits for all lipid emulsions with the mean droplet size at no >500 nm, while large-diameter fat globules as the percent fat>5 microm or PFAT(5) must be <0.05%. A quantitative risk assessment of toxicity from the intravenous infusion of all-in-one (AIO) admixtures made from a lipid emulsion that meets USP standards (fine) vs. one that does not (coarse), was conducted. Two separate 96-h infusion studies in rats receiving nutritionally complete AIOs made from a fine (F) vs. a coarse (C) 20% starting lipid emulsion (SLE) with either 18 or 36% as fat calories were performed. The animals were equally divided in each (18% fat, n=18; 36% fat, n=22) to receive AIOs made from F or C lipids. PFAT(5) levels were measured at the outset and every 24h at the change of infusions and blood levels of liver enzymes AST and GST, and serum triglycerides (TG) were measured at the end of study. On average, the starting PFAT(5) values for infusions of F-AIOs were 0.018+/-0.007 (n=48) vs. C-AIOs at 0.183+/-0.026% (n=48), whereas the 24-h average was 0.234+/-0.211% (n=168) vs. 1.033+/-0.224% (n=180), respectively. No significant differences in the blood-based parameters were noted in rats between F-AIOs and C-AIOs in the studies comparing 18 or 36% of fat calories, respectively. When the data were combined into all F- vs. all C-AIOs, AST was significantly higher in C-AIOs (157+/-41) vs. F-AIOs (130+/-37), p=0.036. TG was lower in C (69+/-37) vs. F (106+/-70), nearly reaching statistical significance (p=0.056) with no differences in GST levels for C (21+/-9) vs. F (17+/-9), p=0.199. When stratified according to a PFAT(5) of <or>0.4%, C-AIOs were significantly higher than F-AIOs for AST (157+/-41 vs. 130+/-37, p=0.004), and TG was significantly lower in C- vs. F-AIOs (67+/-36 vs. 117+/-71, p=0.022), respectively. Coarse lipid emulsions that fail pharmacopeial limits produce less stable AIOs and are associated with evidence of worsened hepatic injury. | 18,849,096 |
High-performance liquid chromatographic and pharmacokinetic analyses of an intravenous submicron emulsion of perillyl alcohol in rats. | Perillyl alcohol (POH) is currently in phase II clinical trials both as a chemopreventative and chemotherapeutic agent. The present report describes a simple, rapid and sensitive HPLC-UV method to quantify POH in rat plasma. After protein precipitation with acetonitrile, POH was separated using an Agilent Zorbax XDB C(18) column (150 mm x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile-water (40:60, v/v) at a flow rate of 1.0 ml min(-1), and detected at 210 nm. The method has been used successfully to determine trace levels of POH in plasma down to 0.015 microg ml(-1). The pharmacokinetics of POH after intravenous administrations in three formulations, i.e. POH solution (POH-SOL), negatively charged submicron emulsions (POH-SE) and positively charged submicron emulsions (POH-CSSE) were investigated. AUC(0-infinity), MRT, t(1/2alpha) and t(1/2beta) of POH-SE and POH-CSSE were significantly higher, while their total body clearance was lower than those of POH-SOL. In addition, AUC(0-infinity), MRT and t(1/2beta) of POH-CSSE were significantly higher than those of POH-SE. The results indicate that the submicron emulsion formulation significantly increases POH blood concentrations and retention within the systemic circulation. | 18,849,133 |
Structure-activity relationship of (-) mammea A/BB derivatives against Leishmania amazonensis. | To study the structure-activity relationship of coumarin (-) mammea A/BB isolated from the CH(2)Cl(2) extract of Calophyllum brasiliense leaves, we evaluated the antileishmanial activity of natural, synthetic and derivatives of this coumarin, against promastigote and intracellular amastigote forms of Leishmania amazonensis, and their cytotoxicity to J774G8 murine macrophages. The derivatives were obtained by hydrogenation and methoxylation reactions. The compound structures were elucidated on the basis of spectroscopic data. The compounds 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), 7-hydroxy-5-methoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin (4) and 5,7-dimethoxy-8-(1-methoxy-2-methylbutyl)-6-(3-methylbut-2-en-1-yl)-4 phenylcoumarin (6) were more biologically active than the compound (-) mammea A/BB (1) (7.4 microM), with IC(50) values from 0.9, 2.4 and 1.9 microM respectively; compound (3) displayed the highest activity. The compounds mammea B/BB (2), 5,7-dimethoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin (5) and 5,7-dihydroxy-4-phenylcoumarin (7) were less active than (-) mammea A/BB (1), with IC(50) of 30.1, 15.1 and 60.2 microM respectively; compound (7) showed the lowest antileishmanial activity of all. Compounds (1), (3), (4) and (6) were active not only against promastigote forms of L. amazonensis, but also against intracellular amastigote forms with IC(50) of 14.3, 0.6, 34.0 and 22.2 microM, respectively. Interestingly, compound (3) showed the most antileishmanial activity of all. This study demonstrated that several aspects of the structure were important for antileishmanial activity. | 18,849,135 |
[Outcome for adults with acute respiratory distress syndrome]. | Acute respiratory distress syndrome in adults (ARDS) is a relatively frequent disease, the mortality of which has diminished considerably in recent years. The long-term outcome of patients who have survived ARDS has been studied extensively and should in the future be taken into account in assessing new treatment modalities. The long-term respiratory sequelae are generally minimal and moderately disabling. Secondary deterioration of respiratory function is not part of the natural history of ARDS and should suggest other diagnoses. The various studies find a clear diminution in quality of life after ARDS (compared with the general population), essentially related to neuromuscular deficiencies associated with the neuromyopathies of resuscitation or to neuropsychological damage combining cognitive disorders and symptoms of posttraumatic stress. These symptoms are not at all specific to ARDS. They are found in varying degrees in patients who have survived intensive care or resuscitation. Appropriate management for these symptoms remains to be determined. Critical care units must now work at preventing the onset of these disorders, by limiting the treatments at risk when possible and by identifying these disorders before discharge to prepare for optimal subsequent management. Patients with ARDS are only a subgroup of more severe illness among all patients in critical care departments. | 18,849,139 |
Assessment of nutritional status in free-living elderly individuals by bioelectrical impedance vector analysis. | The aim of the present research was to examine bioelectrical vector changes in relation to nutritional status in a sample of healthy free-living elderly people. The study group consisted of 170 men and women 70 to 99 y of age. Anthropometric and bioelectrical (resistance and reactance, 50 kHz, 800 muA) measurements were taken. Bioelectrical impedance vector analysis was applied. Nutritional status was determined by the Mini-Nutritional Assessment. Bioelectrical characteristics of normal and undernourished individuals were compared statistically with Hotelling's T(2) test and graphically with 95% probability confidence ellipses. The impedance and multidimensional approaches showed a clear association. Undernourished subjects had a smaller phase angle (men 5.2 +/- 1.3 versus 5.7 +/- 1.0 degrees, P = 0.027; women 5.0 +/- 1.0 versus 5.4 +/- 0.9 degrees, P = 0.065) than normally nourished subjects. Bioelectrical impedance vector analysis represents a promising indicator of nutritional status, suitable in screening programs and clinical practice. | 18,849,147 |
Effect of dietary levels of corn oil on maternal arachidonic acid synthesis and fatty acid composition in lactating rats. | We examined the effect of different amounts of dietary corn oil rich in linoleic acid (LA) on the endogenous synthesis of arachidonic acid (AA), uptake of its precursor LA, and fatty acid composition of tissues involved in the supply of long-chain polyunsaturated fatty acids for milk synthesis. Female Sprague Dawley rats received one of the following diets during pregnancy and lactation: a low-lipid diet (LLD; 2%), an adequate-lipid diet (ALD; 5%), or a high-lipid diet (HLD; 10%). Lipids were provided by corn oil. On day 12 of lactation we measured the endogenous synthesis of AA and quantified the conversion of (13)C-LA to (13)C-AA and the metabolic fate of (13)C-LA from all dietary groups. The LLD rats demonstrated larger amounts of endogenous synthesis of (13)C-AA and more dietary (13)C-LA transferred to the mammary gland (MG) than HLD rats during lactation. The proportion of medium-chain fatty acids was higher in the MG, milk clot, and liver of LLD than of HLD rats. Daily volume and 24-h yield of lipids and energy were lower in LLD rats than in HLD rats. Measurements of milk composition demonstrated that fat concentration significantly increased as lipid concentration increased in the diet. These results suggest that maternal adaptations used to compensate for diets deficient in long-chain polyunsaturated fatty acids include increased endogenous synthesis of AA and elevated uptake of LA in the MG and increased synthesis of medium-chain polyunsaturated fatty acids. It appears that the MG and liver participate together for AA synthesis for milk when this fatty acid is not provided in the diet. | 18,849,148 |
Solidification/stabilisation of air pollution control residues using Portland cement: Physical properties and chloride leaching. | Portland cement (CEMI) was used to solidify air pollution control (APC) residues from an energy-from-waste plant burning municipal solid waste. APC residue/CEMI mixes were prepared with CEMI additions ranging from 0 to 50 weight% (wt%) of total dry mass and water/solids ratios between 0.40 and 0.80. Isothermal conduction calorimetry was used to assess the effect of APC residues on the hydration of CEMI. Although up to 30wt% additions of APC residues accelerated CEMI hydration, the total heat of hydration during the initial 98h was significantly reduced. Higher levels of APC residues severely inhibited CEMI hydration. The consistence, setting time, compressive strength, porosity and chloride leaching characteristics of the solidified products were determined. As might be expected, increasing the CEMI addition and reducing the water content resulted in increased compressive strengths. All mixes achieved compressive strengths greater than 1MPa at 7 and 28days but only 50wt% samples did not show significant strength reduction when tested after immersion in water. Monolithic leaching tests indicated low physical immobilisation of chloride in the CEMI solidified APC residues, with chloride leaching in excess of relevant UK landfill waste acceptance criteria (WAC). The results of this study show that greater than 50% CEMI additions would be required to effectively treat APC residues to meet current WAC limits. | 18,849,156 |
Characteristics and biogas production potential of municipal solid wastes pretreated with a rotary drum reactor. | This study was conducted to determine the characteristics and biogas production potential of organic materials separated from municipal solid wastes using a rotary drum reactor (RDR) process. Four different types of wastes were first pretreated with a commercial RDR system at different retention times (1, 2 and 3 d) and the organic fractions were tested with batch anaerobic digesters with 2.6 g VS L(-1) initial loading. The four types of waste were: municipal solid waste (MSW), a mixture of MSW and paper waste, a mixture of MSW and biosolids, and a mixture of paper and biosolids. After 20 d of thermophilic digestion (50+/-1 degrees C), it was found that the biogas yields of the above materials were in the range of 457-557 mL g VS(-1) and the biogas contained 57.3-60.6% methane. The total solid and volatile solid reductions ranged from 50.2% to 65.0% and 51.8% to 66.8%, respectively. For each material, the change of retention time in the RDR from 1 to 3d did not show significant (alpha=0.05) influence on the biogas yields of the recovered organic materials. Further studies are needed to determine the minimum retention time requirements in the RDR system to achieve effective separation of organic from inorganic materials and produce suitable feedstock for anaerobic digesters. | 18,849,162 |
Discovery of (naphthalen-4-yl)(phenyl)methanones and N-methyl-N-phenylnaphthalen-1-amines as new apoptosis inducers using a cell- and caspase-based HTS assay. | We report the discovery of a series of (naphthalen-4-yl)(phenyl)methanones as potent inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, a group of N-methyl-N-phenylnaphthalen-1-amines also were identified as potent inducers of apoptosis. (1-(Dimethylamino)naphthalen-4-yl)(4-(dimethylamino)phenyl)methanone (2a), one of the most potent analogs, had EC(50) values of 37, 49 and 44nM in T47D, HCT116 and SNU398 cells, respectively. Compound 2a also was highly active in a growth inhibition assay with an GI(50) value of 34nM in T47D cells. Functionally, compound 2a arrested HCT116 cells in G(2)/M followed by induction of apoptosis and inhibited tubulin polymerization. | 18,849,165 |
Chalcogenopyrylium dyes as inhibitors/modulators of P-glycoprotein in multidrug-resistant cells. | A series of chalcogenopyrylium dyes were evaluated as modulators/inhibitors of P-glycoprotein (Pgp). Their ability to inhibit verapamil (VER)-dependent ATPase activity (IC(50) values) in lipid-activated, mouse Cys-less mdr3 Pgp was determined. Their ability to promote calcein-AM (CAM) uptake in MDCKII-MDR1 cells and their capacity to be transported by Pgp in monolayers of MDCKII-MDR1 cells were also evaluated. The chalcogenopyrylium dyes promoted CAM uptake with values of EC(50) between 5 x 10(-6) and 3.5 x 10(-5)M and 7 of the 9 dyes examined in transport studies were substrates for Pgp with efflux ratios (P(BA/AB)) between 14 and 390. Binding of three compounds (1-S, 3-S, and 4-S) to Pgp was also assessed by fluorescence. These three thiopyrylium dyes showed increased fluorescence upon binding to Pgp, giving apparent binding constants, K(app), on the order of 10(-7) to 10(-6)M. Compound 8-Te was particularly intriguing since it appeared to influence Pgp at low micromolar concentrations as evidenced by its influence on VER-stimulated ATPase activity (IC(50) of 1.2 x 10(-6)M), CAM uptake (EC(50) of 5.4 x 10(-6)M), as well as [(3)H]-vinblastine transport by Pgp in cells (IC(50) of 4.3 x 10(-6)M) and within inside-out membrane vesicles (IC(50) of 9.6 x 10(-6)M). Yet, Pgp did not influence the distribution of 8-Te in MDCKII-MDR1 monolayers suggesting that 8-Te may bind to an allosteric site. | 18,849,167 |
The Val allele of HER-2 codon 655 predicts the progression of oral squamous cell carcinoma. | HER-2 proto-oncogene is important for oral carcinogenesis. HER-2 codon 655 polymorphism, either isoleucine (Ile: ATC) or valine (Val: GTC), was associated with the risk of breast carcinoma. This study investigated the clinicopathological implications of this polymorphism in oral carcinoma. We found that 79% of oral carcinoma patients had A/A (Ile/Ile) genotype and 21% had A/G (Ile/Val) genotype, with a G (Val) allelic frequency of 0.10. Univariate analysis indicated a significantly higher Val allelic frequency in cases having nodal metastasis or tumor recurrence; and Val allele was associated with poorer recurrence-free survival of patients. Multivariate analysis after adjusting confounding factors by logistic regression analysis indicated that patients carrying Val allele had a 8.79- and 4.25-fold higher risk for nodal metastasis and recurrence, respectively. Using Cox proportional hazard model, the risk of tumor recurrence was 3.35-fold higher in patients carrying Val allele. This is the first report demonstrating that the Val allele of HER-2 codon 655 could be an independent predictor for oral carcinoma progression. | 18,849,186 |
99mTc(V)-dimercaptosuccinic acid scintigraphy in detecting neck metastases in oral squamous cell carcinoma with clinically negative necks. | This study compares the accuracy of 99mTc(V)-dimercaptosuccinic acid (99mTc(V)-DMSA) Single Photon Emission Computer Tomography (SPECT) by intravenous or local injection in the detection of occult cervical lymph node metastases in clinically N0 squamous cell carcinoma of the oral cavity. Fifty-eight previously untreated patients without clinically detectable cervical metastases were included in the study and were divided into two groups. Twenty-eight patients were in the intravenous injection group and 30 patients were in the local injection (around primary tumors) group. Both groups received 99mTc(V)-DMSA, and 99mTc(V)-DMSA SPECT was performed on all patients. All isolated lymph nodes in neck dissection specimens were stained using H & E. The sensitivity, specificity, and accuracy for intravenous injection of 99mTc(V)-DMSA was 62.5%, 95.0%, and 85.7%, respective, and 84.6%, 82.4%, and 83.3%, respectively, for local injection. SPECT scan of 99mTc(V)-DMSA injected around the tumor is a simple and efficient approach to detecting metastatic lymph nodes in clinically N0 patients with oral cancer. | 18,849,187 |
The effect of preoperative circadian blood pressure pattern on early postoperative outcomes in patients with coronary artery bypass graft surgery. | The aim of this prospective study was to evaluate the relationship between preoperative circadian blood pressure pattern and early postoperative course in patients undergoing coronary artery bypass graft (CABG) surgery. One hundred and thirty patients planning to undergo isolated CABG operation were included to the study (80 men; 50 women). All patients were studied with ambulatory blood pressure monitoring performed 24 hours before surgery and were divided into 2 groups according with presence (79 patients) or absence (51 patients) of dipper phenomenon. Non-dippers were defined as those with a nocturnal reduction of systolic and diastolic blood pressures of less than 10% of daytime pressures. Both groups were compared with each other from the aspect of postoperative need for intraaortic balloon counterpulsation (IABP), inotropic drug support, extubation time, length of intensive care unit and hospitalization stays, renal failure, stroke, malignant ventricular arrhythmia, atrial fibrillation, postoperative myocardial infarction and cardiac mortality. Statistical analyses were performed using Chi-square, unpaired t and Mann-Whitney U tests. Logistic regression analysis was performed to establish associations of non-dipper phenomenon with the risk of postoperative complications. When compared with the dipper patients, need for inotropic medications (37.5% vs. 62.5%), low cardiac output syndrome (30.4% vs. 69.6%), postoperative myocardial infarction (28.6% vs. 71.4%) and malignant ventricular arrhythmias (27.8% vs. 72.2%) were higher in the non-dipper patients (p<0.05 for all). Logistic regression analysis demonstrated that non-dipper phenomenon after CABG was associated with longer cardiopulmonary bypass time (OR=1.038, 95%CI 1.016-1,060, p=0.001), more need for postoperative inotropic agent (OR=4.014, 95%CI 1.235-13,047, p=0.021) and postoperative IABP (OR=6.625, 95%CI 1.564-28.069, p=0.01) support, higher risk of low cardiac output syndrome (OR=4.159, 95%CI 0.921-18.775, p=0.064), malignant ventricular arrhythmia (OR=4.653, 95%CI 0.964-22,456, p=0.056) and postoperative myocardial infarction (OR=7.629, 95%CI 1.448-40.177, p=0.017). Dipper and non-dipper phenomenon can be used as a simple analysis tool for assessing early postoperative mortality and morbidity. | 18,849,227 |
Genetic susceptibility, evolution and the kuru epidemic. | The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the mid-twentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 of the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy-Weinberg disequilibrium. The deviation from Hardy-Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy-Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history. | 18,849,290 |
Trajectories and antecedents of treatment response over time in early-episode psychosis. | Little is known about the extent of heterogeneity of symptomatology in treated early-onset psychosis. The current study aims to quantify the extent of heterogeneity in trajectories of treated symptom severity in early-episode psychosis and their antecedents. Data were from 491 persons with early-episode psychosis from a clinical trial of haloperidol and risperidone. Positive and Negative Syndrome Scale (PANSS) administrations were used to measure symptom severity trajectories for (a) rapid treatment response scores over 4 weeks and (b) medium-term course over 24 weeks. Baseline antecedents included sex, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis, age of onset, the Premorbid Adjustment Scale, and a cognitive test battery. Symptom severity trajectories were calculated with mixed mode latent class regression modeling from which groups were derived. Five groups based on PANSS scores over time were identified. Over 4 weeks, 3 groups with varied baseline PANSS scores (54-105) did not surpass 30% PANSS improvement. Another group improved and then was stable (n = 76,15.3%), and another showed marked improvement (n = 94,18.9%). Logistic regression showed that membership in the best response trajectory was associated with not having a diagnosis of schizophrenia, good premorbid functioning, and higher cognitive functioning, whereas membership in the poor response trajectory was associated with earlier age of onset and poorer cognitive functioning. Amelioration generally characterizes treated symptom severity. Age of onset, diagnosis, cognitive functioning, and premorbid functioning have prognostic value in predicting treatment response trajectories. | 18,849,294 |
Comparative phylogenetic analysis of small GTP-binding genes of model legume plants and assessment of their roles in root nodules. | Small GTP-binding genes play an essential regulatory role in a multitude of cellular processes such as vesicle-mediated intracellular trafficking, signal transduction, cytoskeletal organization, and cell division in plants and animals. Medicago truncatula and Lotus japonicus are important model plants for studying legume-specific biological processes such as nodulation. The publicly available online resources for these plants from websites such as http://www.ncbi.nih.gov, http://www.medicago.org, http://www.tigr.org, and related sites were searched to collect nucleotide sequences that encode GTP-binding protein homologues. A total of 460 small GTPase sequences from several legume species including Medicago and Lotus, Arabidopsis, human, and yeast were phyletically analysed to shed light on the evolution and functional characteristics of legume-specific homologues. One of the main emphases of this study was the elucidation of the possible involvement of some members of small GTPase homologues in the establishment and maintenance of symbiotic associations in root nodules of legumes. A high frequency of vesicle-mediated trafficking in nodules led to the idea of a probable subfunctionalization of some members of this family in legumes. As a result of the analyses, a group of 10 small GTPases that are likely to be mainly expressed in nodules was determined. The sequences determined as a result of this study could be used in more detailed molecular genetic analyses such as creation of RNA interference silencing mutants for further clarification of the role of GTPases in nodulation. This study will also assist in furthering our understanding of the evolutionary history of small GTPases in legume species. | 18,849,296 |
Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds. | Bone marrow-derived mesenchymal stem cells (MSCs) are precursors of bone, cartilage and fat tissue. MSC can also regulate the immune response. For these properties, they are tested in clinical trials for tissue repair in combination with bioscaffolds or injected as cell suspension for immunosuppressant therapy. Experimental data, however, indicate that MSC can undergo or induce a tumorigenic process in determined circumstances. We used a modified model of ectopic bone formation in mice by subcutaneously implanting porous ceramic seeded with murine MSC. In this new model, host-derived sarcomas developed when we implanted MSC/bioscaffold constructs into syngeneic and immunodeficient recipients, but not in allogeneic hosts or when MSCs were injected as cell suspensions. The bioscaffold provided a tridimensional support for MSC to aggregate, thus producing the stimulus for triggering the process eventually leading to the transformation of surrounding cells and creating a surrogate tumor stroma. The chemical and physical characteristics of the bioscaffold did not affect tumor formation; sarcomas developed either when a stiff porous ceramic was used or when the scaffold was a smooth collagen sponge. The immunoregulatory function of MSC contributed to tumor development. Implanted MSC expanded clones of CD4+CD25+ T regulatory lymphocytes that suppressed host's antitumor immune response. | 18,849,298 |
Estimating co-occurring behavioral trajectories within a neighborhood context: a case study of multivariate transition models for clustered data. | Comorbidity is well-documented in psychiatric and risk behavior epidemiology. The authors present a novel application of clustered multivariate transition models to study comorbidity within a clustered context. The authors used data from the Project on Human Development in Chicago Neighborhoods (1995-2002) to assess trajectories in substance use, problems with police, and antisocial behavior among 1,517 participants in 80 neighborhoods followed from ages 12-15 years through ages 18-21 years. The authors used pairwise odds ratios to quantify behavior comorbidity at the individual and neighborhood levels. Risk behaviors co-occurred within individuals at specific points in time: antisocial behavior and substance use were 3.37 times more likely to co-occur within an individual at wave 1, as compared with the co-occurrence of any 2 behaviors from different individuals, while substance use and police problems were 2.94 times more likely to co-occur than substance use and antisocial behavior at wave 2. The authors also evaluated sequential comorbidity. Antisocial behavior was sequentially comorbid with substance use and police problems: 31% of youths who had reported antisocial behavior at baseline reported police problems or drug use at wave 2. These models can prove instrumental in answering the persistent questions about possible sequential relations among problem behaviors. | 18,849,302 |
Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils. | Galectin-3, a beta-galactoside binding, endogenous lectin, takes part in various inflammatory events and is produced in substantial amounts at inflammatory foci. We investigated whether extracellular galectin-3 could participate in the phagocytic clearance of apoptotic neutrophils by macrophages, a process of crucial importance for termination of acute inflammation. Using human leukocytes, we show that exogenously added galectin-3 increased the uptake of apoptotic neutrophils by monocyte-derived macrophages (MDM). Both the proportion of MDM that engulfed apoptotic prey and the number of apoptotic neutrophils that each MDM engulfed were enhanced in the presence of galectin-3. The effect was lactose-inhibitable and required galectin-3 affinity for N-acetyllactosamine, a saccharide typically found on cell surface glycoproteins, since a mutant lacking this activity was without effect. The enhanced uptake relied on the presence of galectin-3 during the cellular interaction and was paralleled by lectin binding to apoptotic cells as well as MDM in a lactose-dependent manner. These findings suggest that galectin-3 functions as a bridging molecule between phagocyte and apoptotic prey, acting as an opsonin. The process of clearance, whereby apoptotic neutrophils are removed by macrophages, is crucial for the resolution of acute inflammation and our data imply that the increased levels of galectin-3 often found at inflammatory sites could potently affect this process. | 18,849,325 |
Ventricular activation is impaired in aged rat hearts. | Ventricular arrhythmias are frequently observed in the elderly population secondary to alterations of electrophysiological properties that occur with the normal aging process of the heart. However, the underlying mechanisms remain poorly understood. The aim of the present study was to determine specific age-related changes in electrophysiological properties and myocardial structure in the ventricles that can be related to a structural-functional arrhythmogenic substrate. Multiple unipolar electrograms were recorded in vivo on the anterior ventricular surface of four control and seven aged rats during normal sinus rhythm and ventricular pacing. Electrical data were related to morphometric and immunohistochemical parameters of the underlying ventricular myocardium. In aged hearts total ventricular activation time was significantly delayed (QRS duration: +69%), while ventricular conduction velocity did not change significantly compared with control hearts. Moreover, ventricular activation patterns displayed variable numbers of epicardial breakthrough points whose appearance could change with time. Morphological analysis in aged rats revealed that heart weight and myocyte transverse diameter increased significantly, scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium, and gap junction connexin expression decreased significantly in ventricular myocardium compared with control rats. Our results show that in aged hearts delayed total ventricular activation time and abnormal activation patterns are not due to delayed myocardial conduction and suggest the occurrence of impaired impulse propagation through the conduction system leading to uncoordinated myocardial excitation. Impaired interaction between the conduction system and ventricular myocardium might create a potential reentry substrate, contributing to a higher incidence of ventricular arrhythmias in the elderly population. | 18,849,337 |
Dialogical nursing ethics: the quality of freedom restrictions. | This article deals with the question of how ethicists respond to practical moral problems emerging in health care practices. Do they remain distanced, taking on the role of an expert, or do they become engaged with nurses and other participants in practice and jointly develop contextualized insights about good care? A basic assumption of dialogical ethics entails that the definition of good care and what it means to be a good nurse is a collaborative product of ongoing dialogues among various stakeholders engaged in the practice. This article discusses the value of a dialogical approach to ethics by drawing on the work of various nursing scholars. We present a case example concerning the quality of freedom restrictions for intellectually disabled people. Issues for discussion include the role and required competences of the ethicist and dealing with asymmetrical relationships between stakeholders. | 18,849,368 |
Producing and using genetic evaluations in the United States beef industry of today. | The overall motivation for the development of an information system for beef cattle improvement is the belief that knowledge of breeding values and heterosis effects allows one to determine the consequences of alternative selection and mating options. With this information, livestock managers can easily shift populations in a desirable direction. The foundation principles for establishing a sound breeding program, including the prediction of animal performance for economically relevant traits and their incorporation into a single index of aggregate economic merit, have been well established over the last half century. Rather than this goal-based approach, the industry adopted a data-driven approach to the production of genetic evaluations that has been characterized by an overemphasis on the evaluation of productive traits, notably BW at various ages, with inadequate regard for other economically important traits, such as reproduction, animal health, and feed requirements. Production of evaluations is breed association centered, and this has delayed the introduction of national across-breed evaluations for all breeds and crosses of cattle. The computational aspects of producing evaluations are now migrating from land-grant universities to breed associations, but not yet to a single entity. The introduction of genomic information in the form of high-density SNP panels will introduce threats, challenges, and new opportunities for the production of evaluations, and represents the largest force to alter the structure of the beef improvement industry since the advent of AI. The use of evaluations has, until recently, stopped short of the provision of index merit as a basis for selection. Accordingly, the value propositions associated with annual improvement or the selection of alternative sires has not been well communicated. Technology, along with economic and other issues related to stakeholder acceptance, will collectively determine the future nature of the industry in terms of the production and use of evaluations. | 18,849,385 |
Performance and carcass traits of finishing heifers fed crude glycerin. | Crossbred heifers (n = 373; 421.6 kg +/- 28.9) were fed finishing diets containing 0, 2, 4, 8, 12, or 16% crude glycerin (DM basis). Diets consisted of steam-flaked corn with 6% alfalfa hay and 1.2% urea and provided 300 mg of monensin, 90 mg of tylosin, and 0.5 mg of melengestrol acetate per animal daily. Cattle were stratified by BW and allocated randomly, within strata, to concrete-surfaced feedlot pens each containing 6 to 7 heifers, with 9 pens per dietary treatment. Cattle were transitioned from the control diet to diets containing increasing proportions of glycerin over a period of 10 d. Cattle had ad libitum access to feed, and diets were delivered once daily throughout the 85-d trial period. As the concentration of glycerin increased, DMI decreased linearly (P < 0.001). Heifers fed 0, 2, 4, 8, 12, and 16% glycerin had ADG of 1.19, 1.34, 1.29, 1.25, 1.17, and 1.03 kg, respectively (linear, P = 0.013; quadratic, P = 0.010). Feeding glycerin had a quadratic effect on G:F, and G:F was optimal when glycerin was fed at 2% of the diet (quadratic, P = 0.046). Glycerin increased the final BW by 12.7, 8.1, and 5.3 kg when fed at 2, 4, and 8% of the diet, respectively, but reduced the final BW by 1.9 and 14.3 kg when included at 12 and 16% of the diet (linear, P = 0.009; quadratic, P = 0.006). Similarly, HCW increased by 8.1, 5.1, and 3.3 kg when glycerin was fed at 2, 4, and 8% of the diet, respectively, but were 1.2 and 9.1 kg less than controls when glycerin was fed at 12 and 16%, respectively (linear, P = 0.009; quadratic, P = 0.006). Longissimus muscle area decreased linearly as glycerin concentrations increased (P < 0.013). Feeding glycerin resulted in linear decreases in subcutaneous fat over the 12th rib and marbling scores (P = 0.045). Glycerin tended to decrease the percentage of cattle grading USDA Choice (P = 0.084) and increase the percentage of cattle grading USDA Select. Adding glycerin to cattle-finishing diets improved BW gain and feed efficiency, particularly when added at concentrations of 8% or less on a DM basis. | 18,849,392 |
Pulmonary rehabilitation in interstitial lung disease: benefits and predictors of response. | Data examining the role of pulmonary rehabilitation (PR) in interstitial lung disease (ILD) are limited. We tested the hypothesis that PR can improve functional status and dyspnea in a large group of patients with ILD, and that certain baseline patient variables can predict this improvement. Data from patients who were referred to PR with a diagnosis of ILD were included. Baseline and post-PR variables were recorded, and changes in 6-min walk test (6MWT) distance and dyspnea were evaluated. The impact of baseline variables on change in 6MWT distance and dyspnea were analyzed. A statistically significant difference was seen in both the change in Borg score and 6MWT distance after PR (p < 0.0001). These changes were consistent with previously established clinically significant differences. Baseline 6MWT distance was a significant predictor of change in 6MWT distance (p < 0.0001), with increasing baseline 6MWT distance predicting a smaller improvement after PR. These results suggest that PR should be considered as a standard of care for patients with ILD. | 18,849,399 |
Arm span to height ratio is related to severity of dyspnea, reduced spirometry volumes, and right heart strain. | Arm span is the closest physiologic measurement to standing height. Increased arm span to standing height ratio, therefore, indicates possible loss of height, which is a feature of aging, often resulting from osteoporosis-related vertebral collapse. We hypothesize that the discrepancy between arm span and height is associated with reduced airflow volumes, severity of dyspnea, and right-sided cardiac structural changes in older individuals with symptoms of dyspnea. Patients with conditions investigated with transthoracic echocardiography for suspected heart failure were invited to participate in our study. All subjects were evaluated with a clinical history and physical examination followed by measurements of arm span, standing height, weight, FEV(1), and FVC. Sixty-six subjects aged 71 +/- 10 years were recruited for our study. Arm span to height ratio was significantly negatively correlated with FEV(1) (r = - 0.464; p < 0.001), FVC (r = - 0.479; p < 0.001), and body weight (r = - 0.252; p < 0.05), and positively correlated with the New York Heart Association classification for dyspnea (rho = 0.309; p < 0.05). Female sex, steroid use, inhaled bronchodilators, orthopnea, paroxysmal nocturnal dyspnea, and right heart chamber dilatation were significantly associated with increased arm span to height ratio. We have found a significant association between increased arm span to height ratio, reduced respiratory airflow volumes, increased severity of dyspnea, and echocardiographic features of pulmonary heart disease in a group of predominantly elderly subjects with multiple comorbidities. The role of arm span measurements in assessments of airflow volumes in older patients and the association between loss of height and dyspnea now deserve further evaluation. | 18,849,402 |
Brain natriuretic peptide levels in managing pediatric patients with pulmonary arterial hypertension. | Pulmonary arterial hypertension (PAH) is an important determinant of morbidity and mortality in children. In this study, we aimed to investigate the value of brain natriuretic peptide (BNP) in a cohort of children with PAH, with respect to monitoring disease severity as assessed by hemodynamic and echocardiographic parameters. We performed a prospective study to determine whether BNP varies over time in this population and whether these changes track with hemodynamic or echocardiographic parameters. The population included a group of 78 pediatric patients from January 2005 to April 2008. All patients had received a diagnosis of PAH and had serum BNP, catheterization, and echocardiographic variables collected longitudinally. The median BNP level, for all observations, was 36 pg/mL (interquartile range, 18 to 76 pg/mL). There was no strong correlation found between commonly used echocardiographic or hemodynamic data and BNP. However, using a bivariate model, the change in BNP measurements over time significantly correlated with the change in the hemodynamic and echocardiographic parameters. Patients with a BNP value > 180 pg/mL had a decreased survival rate. BNP could be a useful marker to monitor disease severity in pediatric PAH. We show that simple correlations between variables and BNP are not likely to illustrate its usefulness due to variations in the normative levels. Instead, we propose that patient BNP levels should be monitored over time, as changes in BNP within a patient are likely to be more informative. | 18,849,405 |
Flexible fitting of high-resolution x-ray structures into cryoelectron microscopy maps using biased molecular dynamics simulations. | A methodology for flexible fitting of all-atom high-resolution structures into low-resolution cryoelectron microscopy (cryo-EM) maps is presented. Flexibility of the modeled structure is simulated by classical molecular dynamics and an additional effective potential is introduced to enhance the fitting process. The additional potential is proportional to the correlation coefficient between the experimental cryo-EM map and a synthetic map generated for an all-atom structure being fitted to the map. The additional forces are calculated as a gradient of the correlation coefficient. During the molecular dynamics simulations under the additional forces, the molecule undergoes a conformational transition that maximizes the correlation coefficient, which results in a high-accuracy fit of all-atom structure into a cryo-EM map. Using five test proteins that exhibit structural rearrangement during their biological activity, we demonstrate performance of our method. We also test our method on the experimental cryo-EM of elongation factor G and show that the model obtained is comparable to previous studies. In addition, we show that overfitting can be avoided by assessing the quality of the fitted model in terms of correlation coefficient and secondary structure preservation. | 18,849,406 |
Finding and characterizing tunnels in macromolecules with application to ion channels and pores. | We describe a new algorithm, CHUNNEL, to automatically find, characterize, and display tunnels or pores in proteins. The correctness and accuracy of the algorithm is verified on a constructed set of proteins and used to analyze large sets of real proteins. The verification set contains proteins with artificially created pores of known path and width profile. The previous benchmark algorithm, HOLE, is compared with the new algorithm. Results show that the major advantage of the new algorithm is that it can successfully find and characterize tunnels with no a priori guidance or clues about the location of the tunnel mouth, and it will successfully find multiple tunnels if present. CHUNNEL can also be used in conjunction with HOLE, with the former used toprime HOLE and the latter to track and characterize the pores. Analysis was conducted on families of membrane protein structures culled from the Protein Data Bank as well as on a set of transmembrane proteins with predicted membrane-aqueous phase interfaces, yielding the first completely automated examination of tunnels through membrane proteins, including tunnels that exit in the membrane bilayer. | 18,849,407 |
The structural impact of a polyglutamine tract is location-dependent. | Polyglutamine (polyQ) expansion leads to protein aggregation and neurodegeneration in Huntington's disease and eight other inherited neurological conditions. Expansion of the polyQ tract beyond a threshold of 37 glutamines leads to the formation of toxic nuclear aggregates. This suggests that polyQ expansion causes a conformational change within the protein, the nature of which is unclear. There is a trend in the disease proteins that the polyQ tract is located external to but not within a structured domain. We have created a model polyQ protein in which the repeat location mimics the flexible environment of the polyQ tract in the disease proteins. Our model protein recapitulates the aggregation features observed with the clinical proteins and allows structural characterization. With the use of NMR spectroscopy and a range of biophysical techniques, we demonstrate that polyQ expansion into the pathological range has no effect on the structure, dynamics, and stability of a domain adjacent to the polyQ tract. To explore the clinical significance of repeat location, we engineered a variant of the model protein with a polyQ tract within the domain, a location that does not mimic physiological context, demonstrating significant destabilization and structural perturbation. These different effects highlight the importance of repeat location. We conclude that protein misfolding within the polyQ tract itself is the driving force behind the key characteristics of polyQ disease, and that structural perturbation of flanking domains is not required. | 18,849,414 |
The Biosynthetic pathway for synechoxanthin, an aromatic carotenoid synthesized by the euryhaline, unicellular cyanobacterium Synechococcus sp. strain PCC 7002. | The euryhaline, unicellular cyanobacterium Synechococcus sp. strain PCC 7002 produces the dicyclic aromatic carotenoid synechoxanthin (chi,chi-caroten-18,18'-dioic acid) as a major pigment (>15% of total carotenoid) and when grown to stationary phase also accumulates small amounts of renierapurpurin (chi,chi-carotene) (J. E. Graham, J. T. J. Lecomte, and D. A. Bryant, J. Nat. Prod. 71:1647-1650, 2008). Two genes that were predicted to encode enzymes involved in the biosynthesis of synechoxanthin were identified by comparative genomics, and these genes were insertionally inactivated in Synechococcus sp. strain PCC 7002 to verify their function. The cruE gene (SYNPCC7002_A1248) encodes beta-carotene desaturase/methyltransferase, which converts beta-carotene to renierapurpurin. The cruH gene (SYNPCC7002_A2246) encodes an enzyme that is minimally responsible for the hydroxylation/oxidation of the C-18 and C-18' methyl groups of renierapurpurin. Based on observed and biochemically characterized intermediates, a complete pathway for synechoxanthin biosynthesis is proposed. | 18,849,428 |
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