title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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The significance of low-level plasma HIV viral load on COBAS TaqMan HIV-1 assays for patients with undetectable plasma viral load on COBAS Amplicor monitor version 1.5. | COBAS TaqMan assay is a new HIV assay for measuring plasma viral load (VL). A significant number of patients with undetectable plasma VL on Amplicor assay were reported to have detectable VL with TaqMan in the study centre. The aim of the present study was to investigate the significance of detectable VL counts with TaqMan assay amongst patients who have had undetectable plasma VL with COBAS Amplicor assay. Observational study on patients who have had undetectable (<less than 50 copies/mL) plasma VL with COBAS Amplicor version 1.5 assay but detectable plasma VL with COBAS TaqMan assay between June 1, 2006 and April 30, 2007. All patients were on highly active antiretroviral therapy (HAART) for longer than 6 months before use of COBAS TaqMan assay. Patients with detectable VL were followed up on a monthly basis until their VL was <40 copes/mL or there was confirmed new resistance to HAART using genotypic and Virco resistance assay. Plasma VL was detectable (>40 copies/mL) in 113 (14%) patients on 126 episodes using TaqMan assay. VL was less than 500 copies/mL in 90% of those episodes. All episodes ended with VL <40 copies/mL after a median of 117 (94-143) days without change in HAART regimes. The duration of those episodes was longer than 150 days in 75% of cases. No new mutation was detected amongst specimens with detectable VL. Short-term detectable VL may be common with using TaqMan assay. This phenomenon did not result in new mutations or failure of HAART in study patients in the short term. | 18,753,122 |
Structural and cell adhesion properties of zebrafish syndecan-4 are shared with higher vertebrates. | The syndecan proteoglycans are an ancient class of receptor, bearing heparan sulfate chains that interact with numerous potential ligands including growth factors, morphogens, and extracellular matrix molecules. The single syndecan of invertebrates appears not to have cell adhesion roles, but these have been described for mammalian paralogues, especially syndecan-4. This member is best understood in terms of interactions, signaling, and structure of its cytoplasmic domain. The zebrafish homologue of syndecan-4 has been genetically linked to cell adhesion and migration in zebrafish embryos, but no molecular and cellular studies have been reported. Here it is demonstrated that key functional attributes of syndecan-4 are common to both zebrafish and mammalian homologues. These include glycosaminoglycan substitution, a NXIP motif in the extracellular domain that promotes integrin-mediated cell adhesion, and a transmembrane GXXXG motif that promotes dimer formation. In addition, despite some amino acid substitutions in the cytoplasmic domain, its ability to form twisted clamp dimers is preserved, as revealed by nuclear magnetic resonance spectroscopy. This technique also showed that phosphatidylinositol 4,5-bisphosphate can interact with the zebrafish syndecan-4 cytoplasmic domain, and that the molecule in its entirety supports focal adhesion formation, and complements the murine null cells to restore a normal actin cytoskeleton identically to the rat homologue. Therefore, the cell adhesion properties of syndecan-4 are consistent across the vertebrate spectrum and reflect an early acquisition of specialization after syndecan gene duplication events at the invertebrate/early chordate boundary. | 18,753,130 |
Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up. | Posaconazole (Noxafil (Schering-Plough Corporation) is a triazole antifungal approved in the United States for the treatment of oropharyngeal candidiasis and for the prophylaxis of Candida and Aspergillus infections in the immunocompromised host. Posaconazole is available only as an oral suspension. When used for the prevention of Candida and Aspergillus infections, posaconazole should be taken three times daily with a high fat meal to maximize oral absorption. Failure to take posaconazole with food will lead to subtherapeutic serum levels and decreased clinical effectiveness of the drug.We report the case of a 49-year-old woman with acute myeloid leukemia who received 4 months of posaconazole as an outpatient for the labeled indication of prophylaxis of Candida and Aspergillus infections. During her last admission, the patient presented with an invasive sinus infection diagnosed as a mixed Aspergillus and Mucor etiology. The patient succumbed to this infection five weeks after presentation. Upon investigation it was found that the patient did not self-administer posaconazole as required in the product labeling, which may have led to drug failure in this patient. We submit this case to illustrate the importance of patient education regarding proper administration of posaconazole. The important role of the outpatient physician, nurse, and pharmacist in this setting is underscored. | 18,753,183 |
CSS-Palm 2.0: an updated software for palmitoylation sites prediction. | Protein palmitoylation is an essential post-translational lipid modification of proteins, and reversibly orchestrates a variety of cellular processes. Identification of palmitoylated proteins with their sites is the foundation for understanding molecular mechanisms and regulatory roles of palmitoylation. Contrasting to the labor-intensive and time-consuming experimental approaches, in silico prediction of palmitoylation sites has attracted much attention as a popular strategy. In this work, we updated our previous CSS-Palm into version 2.0. An updated clustering and scoring strategy (CSS) algorithm was employed with great improvement. The leave-one-out validation and 4-, 6-, 8- and 10-fold cross-validations were adopted to evaluate the prediction performance of CSS-Palm 2.0. Also, an additional new data set not included in training was used to test the robustness of CSS-Palm 2.0. By comparison, the performance of CSS-Palm was much better than previous tools. As an application, we performed a small-scale annotation of palmitoylated proteins in budding yeast. The online service and local packages of CSS-Palm 2.0 were freely available at: http://bioinformatics.lcd-ustc.org/css_palm. | 18,753,194 |
In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46. | Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro and in vivo infection properties of these vectors by increasing their affinity to the Ad35 fiber receptor CD46. We constructed Ad vectors containing either the wild-type Ad35 fiber knob (Ad5/35) or Ad35 knob mutants with 4-fold- and 60-fold-higher affinity to CD46 (Ad5/35+ and Ad5/35++, respectively). In in vitro studies with cell lines, the higher affinities of Ad5/35+ and Ad5/35++ to CD46 did not translate into correspondingly higher transduction efficiencies, regardless of the CD46 receptor density present on cells. However, in vivo, in a mouse model with preestablished CD46(high) liver metastases, intravenous injection of Ad5/35++ resulted in more-efficient tumor cell transduction. We conclude that Ad5/35 vectors with increased affinity to CD46 have an advantage in competing with non-CD46-mediated sequestration of vector particles after intravenous injection. | 18,753,195 |
Region between the canine distemper virus M and F genes modulates virulence by controlling fusion protein expression. | Morbilliviruses, including measles and canine distemper virus (CDV), are nonsegmented, negative-stranded RNA viruses that cause severe diseases in humans and animals. The transcriptional units in their genomes are separated by untranslated regions (UTRs), which contain essential transcription and translation signals. Due to its increased length, the region between the matrix (M) protein and fusion (F) protein open reading frames is of particular interest. In measles virus, the entire F 5' region is untranslated, while several start codons are found in most other morbilliviruses, resulting in a long F protein signal peptide (Fsp). To characterize the role of this region in morbillivirus pathogenesis, we constructed recombinant CDVs, in which either the M-F UTR was replaced with that between the nucleocapsid (N) and phosphoprotein (P) genes, or 106 Fsp residues were deleted. The Fsp deletion alone had no effect in vitro and in vivo. In contrast, substitution of the UTR was associated with a slight increase in F gene and protein expression. Animals infected with this virus either recovered completely or experienced prolonged disease and death due to neuroinvasion. The combination of both changes resulted in a virus with strongly increased F gene and protein expression and complete attenuation. Taken together, our results provide evidence that the region between the morbillivirus M and F genes modulates virulence through transcriptional control of the F gene expression. | 18,753,197 |
Double-stranded RNA adenosine deaminases enhance expression of human immunodeficiency virus type 1 proteins. | ADARs (adenosine deaminases that act on double-stranded RNA) are RNA editing enzymes that catalyze a change from adenosine to inosine, which is then recognized as guanosine by translational machinery. We demonstrate here that overexpression of ADARs but not of an ADAR mutant lacking editing activity could upregulate human immunodeficiency virus type 1 (HIV-1) structural protein expression and viral production. Knockdown of ADAR1 by RNA silencing inhibited HIV-1 production. Viral RNA harvested from transfected ADAR1-knocked-down cells showed a decrease in the level of unspliced RNA transcripts. Overexpression of ADAR1 induced editing at a specific site in the env gene, and a mutant with the edited sequence was expressed more efficiently than the wild-type viral genome. These data suggested the role of ADAR in modulation of HIV-1 replication. Our data demonstrate a novel mechanism in which HIV-1 employs host RNA modification machinery for posttranscriptional regulation of viral protein expression. | 18,753,201 |
Engineered intermonomeric disulfide bonds in the globular domain of Newcastle disease virus hemagglutinin-neuraminidase protein: implications for the mechanism of fusion promotion. | The promotion of membrane fusion by Newcastle disease virus (NDV) requires an interaction between the viral hemagglutinin-neuraminidase (HN) and fusion (F) proteins, although the mechanism by which this interaction regulates fusion is not clear. The NDV HN protein exists as a tetramer composed of a pair of dimers. Based on X-ray crystallographic studies of the NDV HN globular domain (S. Crennell et al., Nat. Struct. Biol. 7:1068-1074, 2000), it was proposed that the protein undergoes a significant conformational change from an initial structure having minimal intermonomeric contacts to a structure with a much more extensive dimer interface. This conformational change was predicted to be integral to fusion promotion with the minimal interface form required to maintain F in its prefusion state until HN binds receptors. However, no evidence for such a conformational change exists for any other paramyxovirus attachment protein. To test the NDV model, we have engineered a pair of intermonomeric disulfide bonds across the dimer interface in the globular domain of an otherwise non-disulfide-linked NDV HN protein by the introduction of cysteine substitutions for residues T216 and D230. The disulfide-linked dimer is formed both intracellularly and in the absence of receptor binding and is efficiently expressed at the cell surface. The disulfide bonds preclude formation of the minimal interface form of the protein and yet enhance both receptor-binding activity at 37 degrees C and fusion promotion. These results confirm that neither the minimal interface form of HN nor the proposed drastic conformational change in the protein is required for fusion. | 18,753,211 |
Recombination, decreased host specificity and increased mobility may have driven the emergence of maize streak virus as an agricultural pathogen. | Maize streak virus (MSV; family Geminiviridae, genus Mastrevirus), the causal agent of maize streak disease, ranks amongst the most serious biological threats to food security in subSaharan Africa. Although five distinct MSV strains have been currently described, only one of these - MSV-A - causes severe disease in maize. Due primarily to their not being an obvious threat to agriculture, very little is known about the 'grass-adapted' MSV strains, MSV-B, -C, -D and -E. Since comparing the genetic diversities, geographical distributions and natural host ranges of MSV-A with the other MSV strains could provide valuable information on the epidemiology, evolution and emergence of MSV-A, we carried out a phylogeographical analysis of MSVs found in uncultivated indigenous African grasses. Amongst the 83 new MSV genomes presented here, we report the discovery of six new MSV strains (MSV-F to -K). The non-random recombination breakpoint distributions detectable with these and other available mastrevirus sequences partially mirror those seen in begomoviruses, implying that the forces shaping these breakpoint patterns have been largely conserved since the earliest geminivirus ancestors. We present evidence that the ancestor of all MSV-A variants was the recombinant progeny of ancestral MSV-B and MSV-G/-F variants. While it remains unknown whether recombination influenced the emergence of MSV-A in maize, our discovery that MSV-A variants may both move between and become established in different regions of Africa with greater ease, and infect more grass species than other MSV strains, goes some way towards explaining why MSV-A is such a successful maize pathogen. | 18,753,214 |
A third genotype of the human parvovirus PARV4 in sub-Saharan Africa. | PARV4 is a recently discovered human parvovirus widely distributed in injecting drug users in the USA and Europe, particularly in those co-infected with human immunodeficiency virus (HIV). Like parvovirus B19, PARV4 persists in previously exposed individuals. In bone marrow and lymphoid tissue, PARV4 sequences were detected in two sub-Saharan African study subjects with AIDS but without a reported history of parenteral exposure and who were uninfected with hepatitis C virus. PARV4 variants infecting these subjects were phylogenetically distinct from genotypes 1 and 2 (formerly PARV5) that were reported previously. Analysis of near-complete genome sequences demonstrated that they should be classified as a third (equidistant) PARV4 genotype. The availability of a further near-complete genome sequence of this novel genotype facilitated identification of conserved novel open reading frames embedded in the ORF2 coding sequence; one encoded a putative protein with identifiable homology to SAT proteins of members of the genus Parvovirus. | 18,753,240 |
TLR4 facilitates translocation of bacteria across renal collecting duct cells. | Uropathogenic Escherichia coli (UPEC) are the most frequent causes of urinary tract infections and pyelonephritis. Renal medullary collecting duct (MCD) cells are the intrarenal site to which UPEC strains prefer to adhere and initiate an inflammatory response, but the ability of UPEC strains to translocate across impermeant MCD cells has not been demonstrated definitively. Here, several UPEC strains adhered to the apical surface and translocated across confluent murine inner MCD cells grown on filters. UPEC strains expressing cytolytic and vacuolating cytotoxins disrupted the integrity of cell layers, whereas noncytolytic UPEC strains passed through the cell layers without altering tight junctions. Apical-to-basal transcellular translocation was dramatically reduced after extinction of Toll-like receptor 4 (TLR4) and the lipid raft marker caveolin-1 by small interfering RNA. Furthermore, disruption of lipid raft integrity by filipin III and methyl-beta-cyclodextrin significantly reduced both the transcellular translocation of UPEC across murine inner MCD cell layers and the stimulation of proinflammatory mediators. Bacterial translocation was also significantly reduced in primary cultures of TLR4-deficient mouse MCD cells compared with MCD cells from wild-type mice. Benzyl alcohol, an anesthetic that enhances membrane fluidity, favored the recruitment of caveolin-1 in lipid rafts and increased the translocation of UPEC across cultured TLR4-deficient MCD cells. These findings demonstrate that the transcellular translocation of UPEC strains across impermeant layers of MCD cells may occur through lipid rafts via a TLR4-facilitated process. | 18,753,256 |
Complement 5a receptor inhibition improves renal allograft survival. | Complement activation plays a key role in mediating apoptosis, inflammation, and transplant rejection. In this study, the role of the complement 5a receptor (C5aR) was examined in human renal allografts and in an allogenic mouse model of renal transplant rejection. In human kidney transplants with acute rejection, C5aR expression was increased in renal tissue and in cells infiltrating the tubulointerstitium. Similar findings were observed in mice. When recipient mice were treated once daily with a C5aR antagonist before transplantation, long-term renal allograft survival was markedly improved compared with vehicle-treatment (75 versus 0%), and apoptosis was reduced. Furthermore, treatment with a C5aR antagonist significantly attenuated monocyte/macrophage infiltration, perhaps a result of reduced levels of monocyte chemoattractant protein 1 and the intercellular adhesion molecule 1. In vitro, C5aR antagonism inhibited intercellular adhesion molecule 1 upregulation in primary mouse aortic endothelial cells and reduced adhesion of peripheral blood mononuclear cells. Furthermore, C5aR blockade markedly reduced alloreactive T cell priming. These results demonstrate that C5aR plays an important role in mediating acute kidney allograft rejection, suggesting that pharmaceutical targeting of C5aR may have potential in transplantation medicine. | 18,753,257 |
Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats. | To understand how female sex hormones influence homeostatic mechanisms of sleep, we studied the effects of estradiol (E(2)) replacement on c-Fos immunoreactivity in sleep/wake-regulatory brain areas after sleep deprivation (SD) in ovariectomized rats. Adult rats were ovariectomized and implanted subcutaneously with capsules containing 17beta-E(2) (10.5 microg; to mimic diestrous E(2) levels) or oil. After 2 wk, animals with E(2) capsules received a single subcutaneous injection of 17beta-E(2) (10 microg/kg; to achieve proestrous E(2) levels) or oil; control animals with oil capsules received an oil injection. Twenty-four hours later, animals were either left undisturbed or sleep deprived by "gentle handling" for 6 h during the early light phase, and killed. E(2) treatment increased serum E(2) levels and uterus weights dose dependently, while attenuating body weight gain. Regardless of hormonal conditions, SD increased c-Fos immunoreactivity in all four arousal-promoting areas and four limbic and neuroendocrine nuclei studied, whereas it decreased c-Fos labeling in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Low and high E(2) treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and locus coeruleus. The high E(2) treatment decreased c-Fos labeling in the VLPO under nondeprived conditions. These results indicate that E(2) replacement modulates SD-induced or spontaneous c-Fos expression in sleep/wake-regulatory and limbic forebrain nuclei. These modulatory effects of E(2) replacement on neuronal activity may be, in part, responsible for E(2)'s influence on sleep/wake behavior. | 18,753,261 |
AtPTR1 and AtPTR5 transport dipeptides in planta. | Transporters for di- and tripeptides belong to the large and poorly characterized PTR/NRT1 (peptide transporter/nitrate transporter 1) family. A new member of this gene family, AtPTR5, was isolated from Arabidopsis (Arabidopsis thaliana). Expression of AtPTR5 was analyzed and compared with tissue specificity of the closely related AtPTR1 to discern their roles in planta. Both transporters facilitate transport of dipeptides with high affinity and are localized at the plasma membrane. Mutants, double mutants, and overexpressing lines were exposed to several dipeptides, including toxic peptides, to analyze how the modified transporter expression affects pollen germination, growth of pollen tubes, root, and shoot. Analysis of atptr5 mutants and AtPTR5-overexpressing lines showed that AtPTR5 facilitates peptide transport into germinating pollen and possibly into maturating pollen, ovules, and seeds. In contrast, AtPTR1 plays a role in uptake of peptides by roots indicated by reduced nitrogen (N) levels and reduced growth of atptr1 mutants on medium with dipeptides as the sole N source. Furthermore, overexpression of AtPTR5 resulted in enhanced shoot growth and increased N content. The function in peptide uptake was further confirmed with toxic peptides, which inhibited growth. The results show that closely related members of the PTR/NRT1 family have different functions in planta. This study also provides evidence that the use of organic N is not restricted to amino acids, but that dipeptides should be considered as a N source and transport form in plants. | 18,753,286 |
Differential effects of urethane and isoflurane on external urethral sphincter electromyography and cystometry in rats. | Urethane is a common and often preferred anesthetic agent for urodynamic recordings in rats, but its use is often restricted to terminal procedures because of a prolonged duration of action and potentially toxic effects. When urodynamic recordings are part of survival procedures in rodent experimental models, inhalation anesthetics, such as isoflurane, are frequently used and generally well tolerated. In this study, we compared the effects of urethane and isoflurane on lower urinary tract function. For this purpose, adult female rats were anesthetized by subcutaneous administration of urethane (n=6) or by inhalation of isoflurane (n=5). Micturition reflexes were assessed by concurrent cystometrogram and external urethral sphincter (EUS) electromyography (EMG) recordings to determine bladder contractile properties, EUS activation patterns, and the coordination between bladder contractions and EUS activation. Compared with urethane, isoflurane reduced frequency of bursts, firing frequency, and amplitude of EUS EMG activity during voiding as well as the EUS EMG amplitude during the bladder filling phase. Isoflurane also prolonged the bladder intercontractile intervals. Other several key functional aspects of the bladder contractile properties as well as the coordination between bladder contractions were not different between the two experimental groups. We conclude that micturition reflexes were differentially affected by isoflurane and urethane. Specifically, isoflurane exhibited a significant suppression of the EUS EMG activity and prolonged the bladder intercontractile intervals compared with urethane. We suggest that these anesthetic properties be taken into consideration during the experimental design and interpretation of urodynamic recordings in rodent models. | 18,753,298 |
Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones. | Astroglia and steroid hormones such as estrogen and progesterone regulate cell growth, function, and protection in the central nervous system (CNS). It appears that astrocytes and steroids act in concert to promote cell survival under pathological conditions. With respect to the role of mitochondrial fusion and fission in energy metabolism, apoptosis, and proliferation, astrocyte mitochondria resemble a perfect intracellular target for steroids to modulate these processes, thereby promoting cell vitality after damage. We have studied the effects of estrogen and progesterone on cell viability in comparison with mitochondrial fusion and fission gene transcription in primary cortical astrocytes from female and male mouse brains. Estrogen- and progesterone-treated female astrocytes demonstrated an increase in cell number and proliferation marker accompanied by an upregulation of fusion and fission gene transcription, which were apparently balancing pro- and anti-apoptotic processes. On the other hand, male astrocytes exhibited no change in cell number after estrogen treatment, but a decrease after progesterone administration. This could be the consequence of stimulated apoptosis in male astrocytes by both steroids, which was counterbalanced by an increased proliferation in the presence of estrogen, whereas it was strengthened in the presence of progesterone. Supportively, estrogen promoted and progesterone decreased the transcription of fusion and fission genes. We suggest that estrogen and progesterone affect mitochondrial fusion and fission gene transcription in cortical astrocytes in a gender-specific way, thereby influencing mitochondrial function differently in both genders. Thus, interaction of sex steroids with mitochondria may represent one possible cause for gender differences in cellular pathology in the CNS. | 18,753,308 |
Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans. | Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Basal IL6 concentration was measured and a low dose (1 microg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. Data are presented as mean+/-S.E.M. Basal IL6 level was 0.84+/-0.10 pg/ml. Basal cortisol was 351.9+/-18.3 nmol/l. Maximal cortisol during synacthen test was 653.0+/-20.6 nmol/l. Maximal cortisol increment was 301.1+/-20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (r=0.63, 95% confidence interval) 0.42-0.83). In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions. | 18,753,312 |
Beta2-integrins contribute to skeletal muscle hypertrophy in mice. | We tested the contribution of beta(2)-integrins, which are important for normal function of neutrophils and macrophages, to skeletal muscle hypertrophy after mechanical loading. Using the synergist ablation model of hypertrophy and mice deficient in the common beta-subunit of beta(2)-integrins (CD18(-/-)), we found that overloaded muscles of wild-type mice had greater myofiber size, dry muscle mass, and total protein content compared with CD18(-/-) mice. The hypertrophy in wild-type mice was preceded by elevations in neutrophils, macrophages, satellite cell/myoblast proliferation (5'-bromo-2'-deoxyuridine- and desmin-positive cells), markers of muscle differentiation (MyoD1 and myogenin gene expression and formation and size of regenerating myofibers), signaling for protein synthesis [phosphorylation of Akt and 70-kDa ribosomal protein S6 kinase (p70S6k)], and reduced signaling for protein degradation (decreased gene expression of muscle atrophy F box/atrogin-1). The deficiency in beta(2)-integrins, however, altered the accumulation profile of neutrophils and macrophages, disrupted the temporal profile of satellite cell/myoblast proliferation, reduced the markers of muscle differentiation, and impaired the p70S6k signaling, all of which could serve as mechanisms for the impaired hypertrophy in overloaded CD18(-/-) mice. In conclusion, our findings indicate that beta(2)-integrins contribute to the hypertrophic response to muscle overload by temporally regulating satellite cells/myoblast proliferation and by enhancing muscle differentiation and p70S6k signaling. | 18,753,316 |
Enhancement of human antigen-specific memory T-cell responses by interleukin-7 may improve accuracy in diagnosing tuberculosis. | Children and immunocompromised adults are at an increased risk of tuberculosis (TB), but diagnosis is more challenging. Recently developed gamma interferon (IFN-gamma) release assays provide increased sensitivity and specificity for diagnosis of latent TB, but their use is not FDA approved in immunocompromised or pediatric populations. Both populations have reduced numbers of T cells, which are major producers of IFN-gamma. Interleukin 7 (IL-7), a survival cytokine, stabilizes IFN-gamma message and increases protein production. IL-7 was added to antigen-stimulated lymphocytes to improve IFN-gamma responses as measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Antigens used were tetanus toxoid (n = 10), p24 (from human immunodeficiency virus [HIV], n = 9), and TB peptides (n = 15). Keyhole limpet hemocyanin was used as a negative control, and phytohemagglutinin was the positive control. IL-7 improved antigen-specific responses to all antigens tested including tetanus toxoid, HIV type 1 p24, and TB peptides (ESAT-6 and CFP-10) with up to a 14-fold increase (mean = 3.8), as measured by ELISA. Increased IFN-gamma responses from controls, HIV-positive patients, and TB patients were statistically significant, with P values of <0.05, 0.01, and 0.05, respectively. ELISPOT assay results confirmed ELISA findings (P values of <0.01, 0.02, and 0.03, respectively), with a strong correlation between the two tests (R(2) = 0.82 to 0.99). Based on average background levels, IL-7 increased detection of IFN-gamma by 39% compared to the level with antigen alone. Increased production of IFN-gamma induced by IL-7 improves sensitivity of ELISA and ELISPOT assays for all antigens tested. Further enhancement of IFN-gamma-based assays might improve TB diagnosis in those populations at highest risk for TB. | 18,753,334 |
Proportions of Mycobacterium massiliense and Mycobacterium bolletii strains among Korean Mycobacterium chelonae-Mycobacterium abscessus group isolates. | Korean isolates of the Mycobacterium chelonae-Mycobacterium abscessus group, which had been isolated from two different hospitals in South Korea, were identified by PCR restriction analysis (PRA) and comparative sequence analysis of 16S rRNA genes, rpoB, and hsp65 to evaluate the proportion of four closely related species (M. chelonae, M. abscessus, M. massiliense, and M. bolletii). Of the 144 rapidly growing mycobacterial strains tested, 127 strains (88.2%) belonged to the M. chelonae-M. abscessus group. In this group, M. chelonae, M. abscessus, M. massiliense, and M. bolletii accounted for 0.8% (n = 1), 51.2% (n = 65), 46.5% (n = 59), and 1.6% (n = 2), respectively. Two isolates which showed discordant results, M. massiliense by rpoB sequence analysis and M. abscessus by hsp65 sequence analysis, were finally identified as M. massiliense based on the additional analysis of sodA and the 16S-23S internal transcribed spacer. M. abscessus group I isolates previously identified by hsp65 PRA were all found to be M. abscessus, whereas group II isolates were further identified as M. massiliense or M. bolletii by sequencing of rpoB and hsp65. Smooth, rough, or mixed colonies of both M. abscessus and M. massiliense isolates were observed. M. massiliense strains that were highly resistant to clarithromycin had a point mutation at the adenine at position 2058 (A(2058)) or 2059 (A(2059)) in the peptidyltransferase region of the 23S rRNA gene. | 18,753,344 |
Femoral prosthesis infection by Rhodotorula mucilaginosa. | This case report is a case history of a femoral prosthesis infection caused by Rhodotorula mucilaginosa in a human immunodeficiency virus patient. Though the pathogenicity of this organism for bone tissue has been previously reported, this is the first reported case of an orthopedic prosthesis infection by this species of the genus Rhodotorula. | 18,753,353 |
Detection of resistance to macrolides in thermotolerant campylobacter species by fluorescence in situ hybridization. | The resistance of enteritis-causing Campylobacter strains to erythromycin is an emerging problem. We therefore evaluated fluorescence in situ hybridization (FISH) for the rapid detection of resistance using 74 campylobacter isolates. FISH showed specificity and sensitivity of 100% for the detection of high-level resistance. | 18,753,354 |
Assay for 5' noncoding region analysis of all human rhinovirus prototype strains. | Increasing recognition of the association of rhinovirus with severe lower respiratory tract illnesses has clarified the need to understand the relationship between specific serotypes of rhinovirus and their clinical consequences. To accomplish this, a specific and sensitive assay to detect and serotype rhinovirus directly from clinical specimens is needed. Traditional methods of serotyping using culture and serum neutralization are time-consuming, limited to certain reference laboratories, and complicated by the existence of over 100 serotypes of human rhinoviruses (HRVs). Accordingly, we have developed a sequence-based assay that targets a 390-bp fragment accounting for approximately two-thirds of the 5' noncoding region (NCR). Our goal was to develop an assay permitting amplification of target sequences directly from clinical specimens and distinction among all 101 prototype strains of rhinoviruses. We determined the sequences of all 101 prototype strains of HRV in this region to enable differentiation of virus genotypes in both viral isolates and clinical specimens. We evaluated this assay in a total of 101 clinical viral isolates and 24 clinical specimens and compared our findings to genotyping results using a different region of the HRV genome (the VP4-VP2 region). Five specimens associated with severe respiratory disease in children did not correlate with any known serotype of rhinovirus and were found to belong to a novel genogroup of rhinovirus, genogroup C. Isolates were also found that corresponded to the genogroup A2 variant identified in New York and Australia and two other novel group A clusters (GAC1 and GAC2). | 18,753,359 |
Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. | Pituitary tumor-transforming gene (PTTG) was only recently discovered. Its overexpression occurs in a wide variety of endocrine and non-endocrine tumors, including ones of pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and the central nervous system. It affects tumor invasiveness and recurrence in several systems, functions as a securin during cell cycle progression, and inhibits premature sister chromatid separation. PTTG is involved in multiple cellular pathways, including proliferation, DNA repair, transformation, angiogenesis induction, invasion, and the induction of genetic instability. In thyroid carcinomas, PTTG expression is a marker of invasiveness. PTTG is overexpressed in most pituitary adenomas, where it appears to correlate with recurrence and angiogenesis. Increasing evidence also points to the role of PTTG in endocrine organ development. For example, PTTG knockout mice show defective pancreatic beta-cell proliferation. Herein, we review the current knowledge regarding PTTG-mediated pathways based on evidence from in vivo and in vitro studies as well as knockout mice models. We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs. In addition, we discuss in vitro and in vivo therapeutic models targeting PTTG overexpression. | 18,753,362 |
Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma. | Anaplastic thyroid cancer (ATC) is a rare but highly aggressive disease with largely unexplained etiology and molecular pathogenesis. In this study, we analyzed genome-wide copy number changes, BRAF (V-raf sarcoma viral oncogene homolog B1) mutations, and p16 and cyclin D1 expressions in a panel of ATC primary tumors. Three ATCs harbored the common BRAF mutation V600E. Using array-comparative genomic hybridisation (array-CGH), several distinct recurrent copy number alterations were revealed including gains in 16p11.2, 20q11.2, and 20q13.12. Subsequent fluorescence in situ hybridization revealed recurrent locus gain of UBCH10 in 20q13.12 and Cyclin D1 (CCND1) in 11q13. The detection of a homozygous loss encompassing the CDKN2A locus in 9p21.3 motivated the examination of p16 protein expression, which was undetectable in 24/27 ATCs (89%). Based on the frequent gain in 11q13 (41%; n=11), the role of CCND1 was further investigated. Expression of cyclin D1 protein was observed at varying levels in 18/27 ATCs (67%). The effect of CCND1 on thyroid cell proliferation was assessed in vitro in ATC cells by means of siRNA and in thyroid cells after CCND1 transfection. In summary, the recurrent chromosomal copy number changes and molecular alterations identified in this study may provide an insight into the pathogenesis and development of ATC. | 18,753,363 |
Recurrent inhibitory network among striatal cholinergic interneurons. | The striatum plays a central role in sensorimotor learning and action selection. Tonically active cholinergic interneurons in the striatum give rise to dense axonal arborizations and significantly shape striatal output. However, it is not clear how the activity of these neurons is regulated within the striatal microcircuitry. In this study, using rat brain slices, we find that stimulation of intrastriatal cholinergic fibers evokes polysynaptic GABA(A) IPSCs in cholinergic interneurons. These polysynaptic GABA(A) IPSCs were abolished by general nicotinic acetylcholine receptor antagonists and also by a specific antagonist of nicotinic receptors containing beta2 subunits. Dopamine receptor antagonists or dopamine depletion failed to block polysynaptic IPSCs, indicating that phasic dopamine release does not directly mediate the polysynaptic transmission. Dual recording from pairs of cholinergic interneurons revealed that activation of a single cholinergic interneuron is capable of eliciting polysynaptic GABA(A) IPSCs both in itself and in nearby cholinergic interneurons. Although polysynaptic transmission arising from a single cholinergic interneuron was depressed during repetitive 2 Hz firing, intrastriatal stimulation reliably evoked large polysynaptic IPSCs by recruiting many cholinergic fibers. We also show that polysynaptic GABAergic inhibition leads to a transient suppression of tonic cholinergic interneuron firing. We propose a novel microcircuit in the striatum, in which cholinergic interneurons are connected to one another through GABAergic interneurons. This may provide a mechanism to convert activation of cholinergic interneurons into widespread recurrent inhibition of these neurons via nicotinic excitation of striatal GABAergic neurons. | 18,753,369 |
Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. | Preferential enhancement of dopamine transmission within the nucleus accumbens (NAc) shell is a fundamental aspect of the neural regulation of cocaine reward. Despite its importance, the nature of this effect is poorly understood. Here, we used fast-scan cyclic voltammetry to examine specific transmission processes underlying cocaine-evoked increases in dopamine transmission within the NAc core and shell. Initially, we examined altered terminal dopamine concentrations after global autoreceptor blockade. This was the first examination of autoreceptor regulation of naturally occurring phasic dopamine transmission and provided a novel characterization of specific components of dopamine neurotransmission. Comparison of increased dopamine signaling evoked by autoreceptor blockade and cocaine administration allowed robust resolution between increased frequency, concentration, and duration of phasic dopamine release events after cocaine delivery. Cocaine increased dopamine transmission by slowed uptake and increased concentration of dopamine released in the core and shell. However, an additional increase in the number phasic release events occurred only within the NAc shell, and this increase was eliminated by inactivation of midbrain dopaminergic neurons. This represents the first evidence that cocaine directly increases the frequency of dopamine release events and reveals that this is responsible for preferentially increased dopamine transmission within the NAc shell after cocaine administration. Additionally, cocaine administration resulted in a synergistic increase in dopamine concentration, and subregion differences were abolished when cocaine was administered in the absence of autoregulation. Together, these results demonstrate that cocaine administration results in a temporally and regionally specific increase in phasic dopamine release that is significantly regulated by dopamine autoreceptors. | 18,753,384 |
Assay validation and biological variation of serum receptor for advanced glycation end-products. | The analytical performance characteristics of an enzyme-linked immunosorbent assay for the receptor for advanced glycation end-products (RAGE) were evaluated. The within- and between-subject components of biological variation were also estimated. Blood was sampled from healthy volunteers into K(2)-ethylenediamine tetraacetic acid (EDTA) and serum separator tubes (SST) and the stability of RAGE in whole blood, plasma and serum examined. Performance characteristics of the assay were assessed using quality control materials. Three samples were obtained from each of 21 healthy volunteers one-week apart, RAGE measured and components of biological variation estimated. RAGE concentrations in blood specimens collected into K(2)-EDTA and SST were stable for at least 6 hours and, after centrifugation, both plasma and serum were stable for at least 24 hours. The RAGE assay had the following characteristics: inter-assay imprecision: coefficient of variation </=7.3%, working range: 26-5000 ng/L, linearity: r = 0.9977 and detection limit: 26 ng/L. Overall within- and between-subject biological variations were 14.6% and 56.5%, the index of individuality was 0.31 and the reference change value was 49.0% at P < 0.05. Samples for RAGE analyses in serum or plasma can be collected without significant difficulties with the assay showing acceptable analytical performance characteristics. Conventional population-based reference values are of limited utility in diagnosis, indicating that RAGE is likely to be more useful in monitoring disease. | 18,753,428 |
Identification and expression profile of a novel alternative splicing of Pax7 in chick skeletal muscle. | Pax7 is essential for skeletal muscle myogenesis. The alternative splicing forms of Pax7 were found in human and mouse. In this study, we identified a new alternative splicing of chick Pax7. We named it Pax7-2 and localized it in the nucleus of chick myoblast. In Pax7-2 mRNA, exon 8 of chick Pax7 gene was spliced out. That led to a 22-amino acid deletion in the COOH terminal of Pax7-2 protein compared with Pax7 protein. Luciferase assays demonstrated that chick Pax7 could act as a transactivator and the deleted 22 amino acids in Pax7-2 may belong to the transactivation domain of Pax7. Pax7-2 lost transactivation ability. We detected the expression levels of Pax7-2 in chick pectoralis muscles at different developmental stages and found that the expression of Pax7-2 was at its peak in d-12 chick embryos. The expression levels of Pax7 and Pax-2 in chick pectoralis muscles at different developmental stages had a similar trend across the period under study, although the changes of their expression levels were different. As chicks grew up, Pax7 and Pax7-2 were expressed at much lower levels. | 18,753,463 |
8-Isoprostane in exhaled breath condensate and exercise-induced bronchoconstriction in asthmatic children and adolescents. | Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway oxidative stress. Exhaled breath condensate (EBC) levels of 8-isoprostane (IsoP), which is a known marker of oxidative stress, might therefore be helpful for monitoring asthma noninvasively. We recruited 46 asthmatic children and adolescents 6 to 17 years of age (29 boys), all of whom underwent lung function testing, measurement of the fractional concentration of exhaled nitric oxide (FENO), and collection of EBCs for 8-IsoP measurement before and after exercise challenge. FENO was measured before exercise and 5 min and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15, and 20 min after exercise. Baseline 8-IsoP levels (but not baseline FENO levels) correlated with the fall in FEV(1) 5 min after exercise (r = - 0.47; p = 0.002). 8-IsoP levels measured after exercise remained unchanged from baseline levels; conversely, FENO levels decreased in parallel with the decline in FEV(1) at 5 min (r = 0.44; p = 0.002). The mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without EIB (n = 34; 44.9 pg/mL [95% confidence interval (CI), 38.3 to 51.5] vs 32.3 pg/mL [95% CI, 27.6 to 37.0], respectively; p < 0.01). No difference was found in the mean baseline FENO between groups (with EIB group: 38.7 ppb; 95% CI, 24.5 to 61.1; without EIB group: 29.1 ppb; 95% CI, 22.0 to 38.4). Increased 8-IsoP concentrations in EBC samples of asthmatic children and adolescents with EIB suggest a role for oxidative stress in bronchial hyperreactivity. | 18,753,466 |
Progesterone regulates FGF10, MET, IGFBP1, and IGFBP3 in the endometrium of the ovine uterus. | Progesterone (P4) is unequivocally required to maintain a uterine environment conducive to pregnancy. This study investigated the effects of P4 treatment on expression of selected growth factors (fibroblast growth factor 7 [FGF7], FGF10, hepatocyte growth factor [HGF], and insulin-like growth factors [IGF1 and IGF2]), their receptors (MET, FGFR2(IIIB), and IGF1R), and IGF binding proteins (IGFBPs) in the ovine uterus. Ewes received daily injections of corn oil vehicle (CO) or 25 mg of P4 in vehicle from 36 h after mating (Day 0) to hysterectomy on Day 9 or Day 12. Another group received P4 to Day 8 and 75 mg of mifepristone (RU486, a P4 receptor antagonist) from Day 8 through Day 12. Endometrial FGF10 mRNA levels increased between Day 9 and Day 12 and in response to P4 on Day 9 in CO-treated ewes, which had larger blastocysts, and were substantially reduced in P4+RU486-treated ewes, which had no blastocysts on Day 12. Endometrial FGF7 or HGF mRNA levels were not affected by day or reduced by RU486 treatment, but MET mRNA levels were higher in P4-treated ewes on Day 9 and Day 12. Levels of IGF1, IGF2, and IGF1R mRNA in the endometria were not affected by early P4 treatment. Although stromal IGFBPs were unaffected by P4, levels of IGFBP1 and IGFBP3 mRNA in uterine luminal epithelia were increased substantially between Day 9 and Day 12 of pregnancy in CO-treated ewes and on Day 9 in early P4-treated ewes. Therefore, FGF10, MET, IGFBP1, and IGFBP3 are P4-regulated factors within the endometrium of the ovine uterus that have potential effects on endometrial function and peri-implantation blastocyst growth and development. | 18,753,603 |
Determination of pyrophosphorylated forms of lipid A in Gram-negative bacteria using a multivaried mass spectrometric approach. | Lipid A isolated from several bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and various strains of Yersinia) showed abundant formation of pyrophosphate anions upon ion dissociation. Pyrophosphate [H(3)P(2)O(7)](-) and/or [HP(2)O(6)](-) anions were observed as dominant fragments from diphosphorylated lipid A anions regardless of the ionization mode (matrix-assisted laser desorption ionization or electrospray ionization), excitation mode (collisional activation or infrared photoexcitation), or mass analyzer (time-of-flight/time-of-flight, tandem quadrupole, Fourier transform-ion cyclotron resonance mass spectrometry). Dissociations of anions from model lipid phosphate, pyrophosphate, and hexose diphosphates confirmed that pyrophosphate fragments were formed abundantly only in the presence of an intact pyrophosphate group in the analyte molecule and were not due to intramolecular rearrangement upon ionization, ion-molecule reactions, or rearrangement following activation. This indicated that pyrophosphate groups are present in diphosphorylated lipid A from a variety of Gram-negative bacteria. | 18,753,624 |
Stamped microbattery electrodes based on self-assembled M13 viruses. | The fabrication and spatial positioning of electrodes are becoming central issues in battery technology because of emerging needs for small scale power sources, including those embedded in flexible substrates and textiles. More generally, novel electrode positioning methods could enable the use of nanostructured electrodes and multidimensional architectures in new battery designs having improved electrochemical performance. Here, we demonstrate the synergistic use of biological and nonbiological assembly methods for fabricating and positioning small battery components that may enable high performance microbatteries with complex architectures. A self-assembled layer of virus-templated cobalt oxide nanowires serving as the active anode material in the battery anode was formed on top of microscale islands of polyelectrolyte multilayers serving as the battery electrolyte, and this assembly was stamped onto platinum microband current collectors. The resulting electrode arrays exhibit full electrochemical functionality. This versatile approach for fabricating and positioning electrodes may provide greater flexibility for implementing advanced battery designs such as those with interdigitated microelectrodes or 3D architectures. | 18,753,629 |
Exclusion of polymorphisms in carnosinase genes (CNDP1 and CNDP2) as a cause of diabetic nephropathy in type 1 diabetes: results of large case-control and follow-up studies. | Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2. Overall, 1,269 Caucasian patients with type 1 diabetes were included in the study, including 613 patients with normoalbuminuria and a long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end-stage renal disease (ESRD). All patients were genotyped for selected polymorphisms, the associations with diabetic nephropathy were tested by a chi(2) test, and odds ratios were calculated. We did not find any significant association between diabetic nephropathy and any examined genetic markers. The negative findings of the case-control study were supported further by negative findings obtained from the 6-year follow-up study of 445 patients with persistent proteinuria, during which 135 patients developed ESRD. Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes. | 18,753,673 |
Incidence of anterior cruciate ligament injuries among elite ballet and modern dancers: a 5-year prospective study. | Ballet and modern dance are jump-intensive activities, but little is known about the incidence of anterior cruciate ligament (ACL) injuries among dancers. Rigorous jump and balance training has been shown in some prospective studies to significantly reduce ACL injury rates among athletes. Dancers advance to the professional level only after having achieved virtuosic jump and balance technique. Therefore, dancers on the elite level may be at relatively low risk for ACL injury. Descriptive epidemiology study. Dance exposure, injuries, and injury conditions were systematically recorded at 4 dance organizations over 5 years. Select neuromuscular and psychometric variables were compared between and within ACL-injured and noninjured dancers. Of 298 dancers, 12 experienced an ACL injury over the 5-year period. The incidence of ACL injury was 0.009 per 1000 exposures. Landing from a jump onto 1 leg was the mechanism of injury in 92% of cases. Incidence was not statistically different between gender or dance groups, although women modern dancers had a 3 to 5 times greater relative risk than women ballet dancers and men dancers. No difference between ACL-injured and noninjured dancers emerged with regard to race, oral contraceptive use, or select musculoskeletal measures. Dancers suffer considerably fewer ACL injuries than athletes participating in team ball sports. The training dancers undertake to perfect lower extremity alignment, jump, and balance skills may serve to protect them against ACL injury. Anterior cruciate ligament injuries happened most often late in the day and season, suggesting an effect of fatigue. | 18,753,681 |
Adeno-associated virus-mediated gene transfer in a rabbit vein graft model. | Stenoses of venous grafts represent a major limitation in coronary artery bypass surgery. The use of viral vectors to facilitate over-expression of factors within the graft to promote long-term patency is a promising new therapeutic concept. One of the viral vector systems is the adeno-associated virus (AAV); a non-pathogenic single stranded DNA virus, which elicits only low immunological responses. Recombinant AAV vector coding for beta-galactosidase was produced and transferred ex vivo using intraluminal application to previously harvested rabbit internal jugular vein grafts (n = 8). The 30 min after application, an end-to-end anastomosis of each graft as a bypass to the carotid artery was performed in a previously established rabbit bypass model. X-Gal-staining of the grafts was performed after killing the animals to quantify gene expression. AAV transduction was successful in 100% of the grafts. After 30 days, beta-galactosidase gene expression could be assessed in the medial layer of the graft. Furthermore, no signs of inflammation could be detected. These findings suggest that recombinant AAV vectors are an alternative to the widely used adenoviral based vectors. These data support the further use of AAV vectors to overcome intimal hyperplasia after vein graft coronary artery bypass surgery. | 18,753,702 |
[Regional cerebral blood flow patterns in extremely elderly patients with Alzheimer's disease]. | Clinical and pathologic features in Alzheimer's disease (AD) patients differ depending on the age of onset. The aim of our study was to compare the regional cerebral blood flow (rCBF) patterns of younger, elderly, and extremely elderly patients with AD with that of controls to characterize the rCBF patterns in extremely elderly patients with AD. Single photon emission CT (SPECT) was performed in 113 patients with probable AD, including 34 younger (<70 years), 41 elderly (70-84 years), and 38 extremely elderly (>or=85 years) patients divided according to age at examination. The SPECT data were analyzed using three-dimensional stereotactic surface projection (3D-SSP). No significant differences regarding gender, duration of disease, education, and Mini-Mental State Examination score were found among the groups. As compared with controls, younger and elderly AD demonstrated significant reduction of rCBF in the temporo-parietal areas, posterior cingulate cortices and precunei, which is considered to be a characteristic rCBF pattern in AD. On the other hand, the extremely elderly AD group demonstrated significant reduction of rCBF in the frontal and medial temporal areas, in addition to the temporo-parietal areas, posterior cingulate cortices and precunei, but the reductions were milder than in those in younger and elderly AD groups. The extremely elderly patients with AD showed atypical rCBF patterns in AD compared to younger and elderly patients with AD. Our data suggest that pathological features in extremely elderly AD may be different from those in younger and elderly AD and that diseases different from AD, such as senile dementia of the neurofibrillary tangle type may be clinically diagnosed as extremely elderly AD. | 18,753,716 |
Relationship between sleep-disordered breathing level and acute onset time of congestive heart failure. | Sleep-disordered breathing (SDB) is frequently observed in patients with congestive heart failure. Recent studies have shown that SDB negatively affects the onset of congestive heart failure; however, no studies have addressed the relationship between the level of SDB and the onset time of acute dyspnea. We hypothesized that SDB affects the acute onset time of dyspnea (AOT) and investigated the relationship between SDB and AOT. We examined 80 patients (mean age, 61.6 years) with congestive heart failure in a clinically stable condition. AOT was divided into 5 time periods (0:00 - 6:00, 6:00 - 12:00, 12:00 - 18:00, 18:00 - 24:00, and unknown). The apnea-hypopnea index (AHI) was obtained based on the results of polysomnography (PSG) to evaluate the severity of SDB. Acute dyspnea occurred in 59 (73.7%) of the 80 patients. When we divided the patients into an AHI < 5 group and an AHI >or= 5 group, there was no significant difference in the AOT; however, a significant difference was observed in those divided into AHI < 20 and AHI >or= 20 groups (P < 0.001). The patients with AHI >or= 20 had more acute dys-pnea between 18:00 - 24:00 and between 0:00 - 6:00 than those with AHI < 20 (32% and 19%, and 4.1% and 4.1%, respectively). Severe SDB patients tended to have acute dyspnea between midnight and dawn. The results suggest SDB might be one of the risk factors of heart failure. | 18,753,730 |
Effect of having a sense of purpose in life on the risk of death from cardiovascular diseases. | Many studies have focused on disease causality, but few of them deal with health-promoting factors. Thus, we examined the effect of having a sense of purpose in life (ikigai) on mortality from cardiovascular disease (CVD). In 1988, we conducted a prospective cohort study of 2,959 Japanese subjects, ranging in age from 40 to 74 years, and followed them till the end of 2003. The level of their sense of purpose in life was evaluated by a self-administered questionnaire. After excluding those with a history of heart disease, stroke, or malignant tumor, 1,618 subjects (832 men and 786 women) who had completed the questionnaire were used in the analyses with Cox's proportional hazards model. During the average 13.3 years of follow up, 249 deaths (172 men and 77 women) occurred as a result of all causes: 32 from heart disease, 31 from stroke, 63 from CVD, and 104 from malignant tumors. The adjusted hazard ratios for death in men with a strong sense of purpose in life, as compared with those with a low sense of purpose, were 0.28 (95% confidence interval: 0.10-0.84) for stroke, 0.56 (0.28-1.10) for CVD, and 0.62 (0.45-0.86) as a result of all causes. In women, no significant relationship was found between having a sense of purpose in life and mortality; this was possibly because the smaller number of deaths reduced the statistical significance. We found that in men, having a sense of purpose in life affected the risk of death as a result of all causes, stroke, and CVD. | 18,753,736 |
Testosterone is a strong correlate of ghrelin levels in men and postmenopausal women. | The secretion and regulation of several hormones such as leptin and growth hormone (GH) is sexually dimorphic. Gender effects on ghrelin, a hormone involved in the regulation of GH secretion and appetite control, are controversial. Our aim was to study the relationship between plasma ghrelin and serum sex steroid hormone concentrations. Forty-five subjects (19 men, 12 premenopausal and 14 postmenopausal women) were evaluated at the Institute of Endocrinology and Metabolism, Tel Aviv Sourasky Medical Center, Israel. After an overnight fast, blood samples were collected for measurements of ghrelin, testosterone, bioavailable testosterone (BT) and estradiol. Statistical analysis was performed with adjustments for age and body mass index. Results are given as mean +/- standard deviation. Ghrelin levels were significantly higher in women (510 +/- 489 pg/ml) than in men (319 +/- 237 pg/ml; p = 0.02). There was a positive correlation between ghrelin and both total testosterone (r = 0.5, p = 0.039) and BT (r = 0.719, p = 0.0011) in male subjects. In premenopausal women, no significant correlations were found between ghrelin and testosterone or BT (r = -0.39, p = 0.2). In contrast, ghrelin strongly and positively correlated with total testosterone (r = 0.7, p = 0.01) and BT (r = 0.821, p = 0.001) in postmenopausal women. Estradiol and ghrelin were positively correlated in the group as a whole (r = 0.356, p = 0.019), but not significantly when analyzed separately by gender. Circulating ghrelin in humans is sexually dimorphic. Testosterone correlates positively with ghrelin levels in men and postmenopausal women. | 18,753,737 |
Bone turnover, osteopenia and vascular calcifications in hemodialysis patients. A histomorphometric and multislice CT study. | Several classical risk factors are at the base of vascular calcifications in hemodialysis patients. Among these, according to a general opinion, also bone turnover plays a role, which, however, requires a better definition. In addition, it has been suggested that there is a relationship between primary osteoporosis and vascular calcifications. This bone biopsy-based study on a hemodialysis patient cohort is a contribution to the evaluation of these alleged relations. This study has been carried out on a cohort of 32 patients on maintenance hemodialysis, who were subjected to transiliac bone biopsy for histomorphometric, histodynamic and bone aluminum deposit evaluation. The patients were also examined with multislice computerized tomography for quantitation of heart and coronary calcifications. The patients were affected by renal osteodystrophy with a wide range of bone formation rate values. A significant negative correlation was found between the rate of bone turnover and log-transformed cardiac calcification score (p < 0.003). There were also negative significant correlations between the cardiac and coronary calcification score log and trabecular number (p < 0.02 and p < 0.05, respectively), while the correlations were positive with trabecular separation (p < 0.03 and p < 0.05, respectively). However, multiregression analysis, forward method, selected only age, hemodialysis age and serum Ca as predictive variables of cardiac and coronary calcification score log, while the histomorphometric and histodynamic variables were excluded. In this study, in spite of the suggestive findings of the univariate statistical approach, a further multivariate analysis was indicative of a spurious association between calcification scores and both bone turnover and histomorphometric parameters of trabecular mass and connectivity. Bone turnover and trabecular mass do not appear to be prominently connected with the extent of cardiac and coronary calcifications in hemodialysis patients. | 18,753,739 |
Tetracycline-inducible gene expression in conditionally immortalized mouse podocytes. | Conditionally immortalized podocytes are valuable research tools but are difficult to efficiently transfect and do not provide graded transgene expression. Conditionally immortalized mouse podocyte cell lines were established employing a tetracycline-inducible system. Glomerular cells, isolated from transgenic mice bear- ing two transgenes, NPHS2-reverse tetracycline-controlled transactivator, rtTA (A transgene) and H2-Kb-thermosensitive SV40 T, ts58A (I transgene), were cloned. One clone (AI podocytes) expressing WT1 and synaptopodin was transfected with pBI-EGFP (enhanced green fluorescent protein, G transgene) and separately with ptTS-Neo (transcriptional suppressor, T transgene) to produce stable transformants, AIG podocytes and AIT podocytes. AIG podocytes expressed EGFP at 33 and 37 degrees C after doxycycline treatment, and retained podocin and rtTA mRNA expression and temperature-sensitive growth regulation. AIT podocytes, transiently transfected with luciferase-BI-EGFP (LG transgene), showed reduced background expression of EGFP and luciferase in the absence of doxycycline. In AITLG podocytes, generated by stable transfection of AIT podocytes with the LG transgene, luciferase expression was tightly regulated by doxycycline in a time- and concentration-dependent manner both at 33 and 37 degrees C, although background expression was not entirely eliminated. These podocytes retained temperature-sensitive growth regulation and expression of podocyte differentiation markers. Mouse podocytes expressed tetracycline-induced transgenes efficiently while retaining differentiation markers. | 18,753,740 |
The human genome and its upcoming dynamics. | The mapping, sequencing and analysis of the human genome is a milestone in biomedical research and a fundamental advance in self-knowledge. Because the sequence was intended to serve as a universal and permanent foundation of biomedical research, enormous international efforts were undertaken to reach the highest level of accuracy and completeness possible. The current assembly of the 24 DNA molecules covers approximately 99% of the euchromatic portion. Including gaps, the euchromatin is approximately 2.88 Gb and the overall size of the human genome approximately 3.08 Gb. Repeated sequences account for more than half of the human genome. Remarkable is the high proportion of segmental duplications. Until recently it was assumed that tiny variations in an otherwise universal reference sequence are the genetic bases of individual human traits. Now, with the nearly-complete reference in hands, it becomes increasingly evident, that our concept of genome plasticity has to be extended from seemingly fixed human segmental duplications to interindividual, large-scale structural polymorphisms. | 18,753,765 |
Cracking the genomic piggy bank: identifying secrets of the pig genome. | Though researchers are uncovering valuable information about the pig genome at unprecedented speed, the porcine genome community is barely scratching the surface as to understanding interactions of the biological code. The pig genetic linkage map has nearly 5,000 loci comprised of genes, microsatellites, and amplified fragment length polymorphism markers. Likewise, the physical map is becoming denser with nearly 6,000 markers. The long awaited sequencing efforts are providing multidimensional benefits with sequence available for comparative genomics and identifying single nucleotide polymorphisms for use in linkage and trait association studies. Scientists are using exotic and commercial breeds for quantitative trait loci scans. Additionally, candidate gene studies continue to identify chromosomal regions or genes associated with economically important traits such as growth rate, leanness, feed intake, meat quality, litter size, and disease resistance. The commercial pig industry is actively incorporating these markers in marker-assisted selection along with traditional performance information to improve said traits. Researchers are utilizing novel tools including pig microarrays along with advanced bioinformatics to identify new candidate genes, understand gene function, and piece together gene networks involved in important biological processes. Advances in pig genomics and implications to the pork industry as well as human health are reviewed. | 18,753,772 |
The chicken genome. | The chicken has long been an important model organism for developmental biology, as well as a major source of protein with billions of birds used in meat and egg production each year. Chicken genomics has been transformed in recent years, with the characterisation of large EST collections and most recently with the assembly of the chicken genome sequence. Since the chicken shared a common ancestor with mammals 310 million years ago it fills a gap in our knowledge in the evolution and conservation of vertebrate genomes. As the first livestock genome to be fully sequenced it leads the way for others to follow. The genome sequence and the availability of 3 million genetic polymorphisms are expected to aid the identification of genes that control traits of importance in poultry. As the first bird genome to be sequenced it is a model for the remaining 9,600 species thought to exist today. Many of the features of avian biology and organisation of the chicken genome make it an ideal model organism for phylogenetics and embryology, along with applications in agriculture and medicine. In this report these advances are reviewed and the implications of the chicken genome in current and future applications are discussed. | 18,753,775 |
Insights from Xenopus genomes. | Amphibians have been used since the 19th century as vertebrate models for the experimentalist. Since 50 years or so, Xenopus laevis is the most widely used anuran amphibian research organism. However, because it is a pseudo-tetraploid species, its genetics has been lagging behind. Contemporary studies shift their focus to the only Xenopus species known to be diploid, the small African tropical clawed frog Xenopus tropicalis. A complete genome project is undertaken, with genetic and physical mapping going alongside cDNA and genome sequencing. Currently, X. tropicalis is the most distantly related vertebrate species to humans that still exhibits long-range synteny. Much of amphibian genetics can be learned from this genomic undertaking, and could shed light on fascinating biological processes such as embryogenesis, regeneration and metamorphosis. Moreover, Xenopus species are exciting models for the study of gene duplication because new species can evolve through allopolyploidization, a type of genome duplication that can result from hybridization among species. The current genomic resources for Xenopus briefly described here, combined with the practical experimental advantages of this non-mammalian vertebrate model, make it ideally suited for systematic functional genomic studies. | 18,753,776 |
Divergence of regulatory sequences in duplicated fish genes. | Duplicated genes can undergo different fates, from nonfunctionalization to subfunctionalization and neofunctionalization. In particular, changes in regulatory sequences affecting the expression domain of genes seem to be responsible for the latter two fates. In this study we used in silico motif detection to show how alterations in the composition of regulatory motifs between paralogous genes in zebrafish and Tetraodon might reflect the functional divergence of duplicates. | 18,753,786 |
[Effects of eye protective device and ear protective device application on sleep disorder with coronary disease patients in CCU]. | The purpose of this research was to analyze the effects of an eye protective device and ear protective device application on sleep disorder with coronary disease patients in CCU. The research design was set up as a nonequivalent control group non-synchronized design. The subjects were coronary disease patients in the CCU of a tertiary hospital. The subjects were composed of 20 in the group with an eye protective device, 18 in the group with an ear protective device, 17 in the group with an eye protective device and ear protective device and 20 in the control group. The data was analyzed by chi2-test, ANOVA, Repeated measures ANOVA, Sheffe-test, Simple main effect and Time contrast using SPSS Win 12.0. The hypothesis, 'There are significant differences in sleep quantity among the four groups' was supported (F=1,342.71, p=.000). The hypothesis, 'There are significant differences in the subjective evaluation of the general sleep patterns among the four groups' was supported (F=3,638.73, p=.000). In addition the hypothesis, 'There are significant differences in degree of sleep among the four groups' was supported (F=1,616.61, p=.000). It is cost effective and a simple eye protective device and ear protective device should be applied to patients according to their preference and characteristics in the clinical setting. | 18,753,810 |
Evaluation of serotonin-2A receptor occupancy with 123I-5-I-R91150 and single-photon emission tomography before and after low-dose pipamperone administration in the canine brain. | To conduct a cost-efficient pilot study on the effect of low-dose pipamperone on the serotonin-2A receptor binding in a large animal model with conventional single-photon emission tomography modalities. Three healthy drug-naive female Beagle dogs were scanned before and after administration of a single-dose pipamperone of 5 and 10 mg. Acquisition was performed under general anesthesia 90 min after injection of the specific radioligand 123I-5-I-R91150 with a triple head gamma-camera (Triad, Trionix). Binding index and receptor occupancy were calculated on the emission data after image fusion with the emission data from the individual 99mTc-ethyl cysteinate dimer perfusion scans to optimize frontal cortex delineation. A dose-dependent reduction of the binding index was observed after single low-dose pipamperone, suggestive for competition of this cold compound with the radioligand for the 5-HT2A receptor. The calculated mean-binding serotonin-2A binding index in the frontal cortex was 1.47 before treatment and reduced to 1.28 after one dose of pipamperone 5 mg and to 1.08 after one dose of pipamperone 10 mg. The calculated occupancy was 40.4% after one dose of 5 mg pipamperone and 83% after one dose of 10 mg pipamperone. This experiment supports the hypothesis that pipamperone, even in the low-dose range, significantly blocks serotonin-2A receptors. This study also demonstrates the value of the canine model to investigate the effects of drugs on neurotransmitter systems. Repeated nuclear imaging brain scanning experiments with different paradigms and medication doses are possible with conventional imaging equipment in a well-accepted laboratory species. | 18,753,826 |
Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents. | To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated. Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported. TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response. | 18,753,862 |
Credentialing and certification: issues for clinical nurse specialists. | This article will provide a brief overview of the concepts of credentialing and certification and will identify some of the issues around certification and credentialing for clinical nurse specialists (CNSs). The article will also describe some of the misconceptions about certification and licensure that cause problems to CNSs, identify the current questions on the debated regulation of CNSs, and outline some of the proactive steps that can be taken to stay ahead of the current wave of change anticipated with the suggested changes in the forthcoming regulation of CNSs. Information provided is pertinent for new graduates and seasoned CNSs and provides an opportunity for both to gain a better understanding of certification and credentialing. | 18,753,882 |
Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility. | The contribution of clade-specific polymorphisms in the HIV-1 integrase gene towards integrase inhibitor phenotypic susceptibility was tested on 137 clinical isolates, of which 60 were non-clade B strains. Control Q148R mutant virus showed fold change values of 17.85 +/- 2.77 and 88.94 +/- 9.02 for raltegravir and elvitegravir, respectively, whereas the average fold change for the clinical samples was 0.91 +/- 0.40, and 0.84 +/- 0.37. Phenotypic testing proved that clade-specific integrase polymorphisms do not contribute to reduced susceptibility towards integrase inhibitors. | 18,753,927 |
Lack of genetic association between exaggerated placental site reaction and placental site trophoblastic tumor. | Exaggerated placental site (EPS) reaction is a reactive or an exuberant physiologic process involving intermediate trophoblasts infiltrating the underlying endomyometrium at the implantation site. Sharing similar cytological and immunohistochemical features with the tumor cells of placental site trophoblastic tumor, a biological link between the 2 lesions can be speculated. Because placental site trophoblastic tumor has a unique sex chromosomal requirement in its genome that requires a paternal X chromosome (i.e. a female antecedent gestation), we investigated whether EPS carries the similar genetic profile by DNA genotypic analysis. Twenty cases of EPS were reviewed and analyzed by AmpFlSTR Identifiler polymerase chain reaction amplification system (Applied Biosystems, Inc., Foster City, CA). The genetic profile of all cases demonstrated unique paternal alleles to that of the paired maternal tissue, confirming the trophoblastic origin of EPS. The presence of an XY genome (male) was identified in 11 cases (55%), and an XX genome (female) was seen in the rest of 9 cases (45%). Therefore, EPS is a trophoblastic lesion that can arise from either male or female gestations. The assignment of sex chromosomes in our study (XY, 55% and XX, 45%) does not support a neoplastic association between placental site trophoblastic tumor and EPS. | 18,753,963 |
Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). | Recent retrospective studies of heterogeneously treated patients have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). Here, we investigated the prognostic impact of MYC aberrations analyzed by interphase fluorescence in situ hybridization in 177 patients with de novo DLBCL treated within the two prospective, randomized trials non-Hodgkin's lymphoma NHL-B1 and NHL-B2. MYC aberrations were detected in 14 DLBCL (7.9%). In a univariate analysis compared with MYC-negative DLBCL, MYC-positive cases showed a significantly shorter overall survival (OS) (P=0.047) and relevantly, though not significantly, shorter event-free survival (EFS) (P=0.062). In a Cox model adjusted for the international prognostic index, the presence of a MYC gene rearrangement was the strongest statistically independent predictor of OS (relative risk 3.4, P=0.004) and EFS (relative risk 2.5, P=0.015), and this also held true when the cell-of-origin signature detected by immunohistochemistry was included in the model. | 18,754,028 |
NKG2D ligands expression and NKG2D-mediated NK activity in Sezary patients. | Sezary syndrome (SS) is a rare lymphoma characterized by the clonal expansion in the skin and in blood of CD4(+)CD158k(+) T cells. Natural killer (NK) activation against tumors in leukemia models is partly based on the recognition of the target through the NKG2D/NKG2D ligands interactions. We analyzed ex vivo SS malignant lymphocytes for the expression of the NKG2D ligands such as the major histocompatibility complex class I-related molecules (MIC) A and B and the UL16 binding proteins (ULBP). The expressions of NKG2D, the natural cytotoxicity receptors (NKp30, NKp44, and NKp46) and the activating receptor DNAM-1 were simultaneously investigated on circulating patients NK and CD8(+) nonmalignant lymphocytes. Interestingly, although at least one of the NKG2D ligands was expressed on the circulating malignant lymphocytes of 9 out of 10 patients, NKG2D was expressed on effector lymphocytes. We found that soluble MICA in patient's sera was increased, which may constitute a mechanism to escape the immune response. In vitro, SS tumor lymphocytes induced the degranulation of perforin by the NKL cell line. More importantly, NKG2D expressed on SS patients NK cells is functional and capable to induce degranulation. Altogether, these data could suggest that stimulating NK function in SS patients may be a promising strategy to reduce tumor invasion. | 18,754,036 |
Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. | The incidence of malignant melanoma has increased dramatically over the past four decades. Metastatic melanoma is associated with poor prognosis, as the current treatments do not have a significant impact on prolonging survival or decreasing mortality. We have identified a member of the transforming growth factor-beta superfamily, macrophage inhibitory cytokine (MIC)-1, which is highly expressed in melanoma cells. Of 53 melanoma cell lines that were examined for relative MIC-1 expression by western blot analysis, 35 (66%) showed significantly higher levels of MIC-1 compared to normal melanocytes. Primary melanoma biopsies (15 of 22) were found to contain cells expressing low levels of MIC-1 as determined by immunohistochemistry. In contrast, all metastatic melanoma biopsies examined (16 of 16) had strong expression of MIC-1. Expression of MIC-1 was found to be dependent on the mitogen-activated protein kinase pathway, and is a transcriptional target of the microphthalmia-associated transcription factor. Knockdown of MIC-1 expression using stable short-hairpin RNA in three melanoma cell lines showed a significant decrease in tumorigenicity (P<0.0001). These results indicate that MIC-1 may function to promote development of more aggressive melanoma tumors. MIC-1 may be suitable for development as a serum diagnostic and is a possible target for the treatment of metastatic melanoma. | 18,754,039 |
Abrogation of the resistance of choline-induced Pseudomonas aeruginosa virulence to sub-MIC erythromycin by ethanol. | Despite Pseudomonas aeruginosa antibiotic resistance, erythromycin (ERM, a macrolide) at subinhibitory concentration (sub-MIC) reduces its pathogenicity. We assessed ERM effects on P. aeruginosa in cultures containing choline (Ch) without and with 1% ethanol (Et) addition. Ch, as an osmoprotectant, increases the following virulence factors (VIFs): lectins (haemagglutination); proteases (casein and elastin lysis); haemolytic phospholipase C (PLC-H; haemolysis); pyocyanin (pigment o.d.) and autoinducers (violacein bioassay). Ethanol also increases lectins, proteases, pyocyanin, autoinducers and rhamnolipid (RHAL; haemolysis) formation, but reduces Ch-induced PLC and protease (elastase) activities. ERM has been shown to totally suppress the Et-induced VIFs, whereas partially reducing the Ch-induced ones. Unexpectedly, ERM combination with 1% Et dramatically annuls the Ch-induced factors. Et contribution might be attributed to its effect on cell membrane, displaying synergism with ERM, whereas antagonizing Ch osmoprotective potential and shifting gene expression. This information is worth further molecular investigation and clinical consideration for skin infection therapy. | 18,754,042 |
Immunotherapy: a way to improve the therapeutic outcome of photodynamic therapy? | Photodynamic therapy (PDT) is a treatment for cancer and non-cancerous lesions involving light and a sensitizing drug, a so-called photosensitizer. Photosensitizers for PDT usually accumulate in tumour tissues with some selectivity. Thus, malignant and abnormal cells can be destroyed by PDT which acts by producing singlet oxygen and possible other reactive oxygen species. However, the efficiency of PDT is often limited by shallow light penetration into tissue. In some cases one treatment modality cannot cure a patient because of treatment limitations and/or side effects. In recent years, many preclinical studies have indicated that the therapeutic outcome of PDT can be improved, doses and side effects lowered by combination with immunotherapy. Most experiments have been done with animals and cell lines. This review summarizes the current knowledge about different immunotherapeutic approaches which can be used to improve effectiveness and extend the applications of PDT in clinics. | 18,754,046 |
Cryopreservation of black chokeberry in vitro shoot apices. | In vitro shoot apices of black chokeberry (Aronia melanocarpa Elliott) were successfully cryopreserved utilizing three methods, namely vitrification, encapsulation-vitrification and encapsulation-dehydration. Encapsulation-dehydration and encapsulation-vitrification, however, seem preferable to vitrification, since the highest respective survival levels of apices (71.1 +/- 2.2 percent and 77.8 +/- 4.4 percent) by both methods were higher than that (60.0 +/- 3.9 percent) by vitrification. In encapsulation-dehydration, the highest survival was achieved when the moisture content of beads was reduced to 19 percent by drying with silica gel for 6 h. In the present study, it was shown that adding 1.0 M glycerol to beads and loading solution during encapsulation-dehydration resulted in high survival (91.7 - 95.0 percent) regardless of lines and polyploids of black chokeberry. | 18,754,061 |
Clinically relevant variations of the superior thyroid artery: an anatomic guide for surgical neck dissection. | The superior thyroid artery (STA) is the dominant arterial supply of the thyroid gland, upper larynx and the neck region. The knowledge of variations in possible patterns of origin, courses, and branching pattern of the STA is also important for surgical procedures in the neck region, such as emergency cricothyroidotomy, radical neck dissection, catheterization, reconstruction of aneurysm and carotid endarterectomy. The surgical anatomy of the STA was studied in 20 adult Anatolian preserved cadavers between the age of 40 and 70 years. The outer diameter of the STA origin was observed to be 3.53 +/- 1.17 mm. The location of the origin of the STA according to the carotid bifurcation was evaluated as above (25%), below (35%) and at the same level (40%). The distribution patterns of the STA were classified into six types depending on the branching pattern. The outer diameter of the infrahyoid branch, superior laryngeal artery, sternocleidomastoid artery and cricothyroid branch at their origins were observed to be 1.13 +/- 0.14, 1.42 +/- 0.47, 1.54 +/- 0.96 and 1.30 +/- 0.41 mm, respectively. Typical and variant glandular branching patterns were observed in 85 and 15% of the specimens, respectively. The outer diameters of anterior, anteromedial, anterolateral and posterior glandular branches were measured as 2.05 +/- 0.46, 1.41 +/- 0.43, 1.51 +/- 0.41 and 1.73 +/- 0.53 mm, respectively. It is necessary to understand the surgical anatomy of the STA to carry out successful radical neck dissection and to minimize postoperative complications in a bloodless surgical field. | 18,754,071 |
Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis. | A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure. | 18,754,075 |
Deactivation kinetics and response surface analysis of the stability of alpha-L-rhamnosidase from Penicillium decumbens. | The stability of the mixed enzyme preparation Naringinase from Penicillium decumbens was studied in dependence of the temperature, the pH value, and the enzyme concentration by means of response surface methodology. Deactivation kinetics by formation of an intermediate state was proposed for fitting deactivation data. Empirical models could then be constructed for prediction of deactivation rate constants, specific activity of intermediate state, and half-life values under different incubation conditions. From this study, it can be concluded that (1) Naringinase is most stable in the pH range of 4.5-5.0, being quite sensitive to lower pHs (<3.5) and (2) the glyco-enzyme is a rather thermo-stable enzyme preserving its initial activity for long times when incubated at its optimal pH up to temperatures of 65 degrees C. Enriched alpha-L-rhamnosidase after column treatment and ultrafiltration presented similar deactivation kinetics pattern and half-life values as the unpurified enzyme. Thus, any influence of low molecular weight substances on its deactivation is most probably negligible. The intermediate state of the enzyme may correspond to unfolding and self-digestion of its carbohydrate portion, lowering its activity relative to the initial state. The digestion- and unfolding-grade of this intermediate state may also be controlled by the pH and temperature of incubation. | 18,754,082 |
Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation. | The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation. | 18,754,094 |
[Cellular mechanisms of tumor response: clinical demands]. | Diseases caused by cancer have become more common due to an increase in life-expectation, but the probability of reaching an old age with or without a tumor disease is still increasing. According to the statistics of the German Cancer register, at present more than half of cancer patients survive for at least 5 years after cancer has been diagnosed. Many tumors can be cured using innovative neoadjuvant and adjuvant therapy regimes, but the options for palliative therapy have also been improved. This leads to an increasing importance of the evaluation of the tumor response using imaging techniques. Classically, tumor response is measured by imaging using the RECIST (response evaluation criteria in solid tumors) criteria, which define the changes in size of the tumor during therapy. However, there is increasingly more evidence that RECIST as the only measure of tumor response, does not document tumor response for all tumor entities and especially not for many medications known as targeted therapy. This article gives a review of the principles and mode of effect of various therapy regimes as well as the clinical demands on imaging techniques. | 18,754,097 |
Resistance to Thielaviopsis basicola in the cultivated A genome cotton. | Black root rot (BRR), incited by the soilborne pathogen Thielaviopsis basicola has the potential to cause significant economic loss in cotton (Gossypium spp.) production. Cultivated tetraploids of cotton (G. hirsutum and G. barbadense) are susceptible although resistant types have been identified in a possible tetraploid progenitor, G. herbaceum. Genetic mapping was used to detect the chromosomal locations of quantitative trait loci (QTL) that confer resistance to the BRR pathogen. A population of F(2) individuals (G. herbaceum x G. arboreum) and F(2:3) progeny families were examined. Phenotypic variation between resistant and susceptible reactions could be explained partly by three QTL. The BRR5.1, BRR9.1, and BRR13.1 QTL each explained 19.1, 10.3 and 8.5% of the total phenotypic variation, respectively. The combination of all three in a single genetic model explained 32.7% of the phenotypic variation. Comparative analysis was conducted on significant QTL regions to deduce the cotton-Arabidopsis synteny relationship and examine the correspondence between BRR QTL and Arabidopsis pathogen defense genes. Totally 20 Arabidopsis synteny segments corresponded within one of three BRR QTL regions. Each synteny segment contains many potential Arabidopsis candidate genes. A total of 624 Arabidopsis genes, including 22 pathogen defense and 36 stress response genes, could be placed within the syntenic regions corresponding to the BRR QTL. Fine mapping is needed to delineate each underlying BRR R-gene and possible Arabidopsis orthologs. Research and breeding activities to examine each QTL and underlying genes in Upland cotton (G. hirsutum) are ongoing. | 18,754,098 |
Protective effect of resveratrol in endotoxemia-induced acute phase response in rats. | Lipopolysaccharide (LPS), a glycolipid component of the cell wall of gram-negative bacteria can elicit a systemic inflammatory process leading to septic shock and death. Acute phase response is characterized by fever, leucocytosis, thrombocytopenia, altered metabolic responses and redox balance by inducing excessive reactive oxygen species (ROS) generation. Resveratrol (trans-3,5,4' trihydroxystilbene) is a natural polyphenol exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effect of resveratrol on endotoxemia-induced acute phase response in rats. When acutely administered by i.p. route, resveratrol (40 mg/kg b.w.) counteracted the effect of a single injection of LPS (4 mg/kg b.w.) which induced fever, a decrease in white blood cells (WBC) and platelets (PLT) counts. When i.p. administered during 7 days at 20 mg/kg per day (subacute treatment), resveratrol abrogated LPS-induced erythrocytes lipoperoxidation and catalase (CAT) activity depression to control levels. In the plasma compartment, LPS increased malondialdehyde (MDA) via nitric monoxide (NO) elevation and decreased iron level. All these deleterious LPS effects were reversed by a subacute resveratrol pre-treatment via a NO independent way. Resveratrol exhibited potent protective effect on LPS-induced acute phase response in rats. | 18,754,105 |
Vincristine-induced fatal neuropathy in non-Hodgkin's lymphoma. | The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. We describe a case of vincristine-induced multiple cranial and autonomic neuropathy, and sensory-motor axonal peripheral neuropathy (pan-neuropathy), which is an extremely rare fatal complication of this drug. The patient developed fulminant cranial, peripheral and significant autonomic neuropathy. | 18,754,106 |
Speculating to accumulate: reducing the cost of wound care by appropriate dressing selection. | The key determinants of wound-care costs are well known. When undertaking local audits, practitioners are advised to collect data against each of these determinants and then use them to formulate cost-effective dressing formularies. | 18,754,198 |
Euthanasia: a summary of the law in England and Wales. | When medical treatment becomes futile, or the patient's suffering is intractable, doctors face the agonising dilemma of whether to proceed with euthanasia. It is important for a doctor to be familiar with the law surrounding euthanasia, in order to avoid prosecution. This paper explores the law in England and Wales regarding the different categories of euthanasia: voluntary euthanasia, nonvoluntary euthanasia, passive euthanasia, and active euthanasia. | 18,754,203 |
The vulnerable adult in police custody: lessons learned from the case of R v Paul James Aspinall. | This case review highlights some of the problems that vulnerable adults, especially those with a mental disorder as defined in section 1 (2) of the Mental Health Act 1983, face in police custody. These service users already experience some form of discrimination within the wider society in terms of access to community services. The role of the appropriate adult in providing support to the person in custody is fundamental, as enshrined in the Police and Criminal Evidence Act 1984 Code of Practice. It is one of the important safeguards of the legislation often referred to as a 'gateway safeguard' because it leads to other safeguards. The roles and functions of the custody officer are reviewed. | 18,754,204 |
Appeals to the Mental Health Review Tribunal in an ageing population. | The United Kingdom (UK) population is ageing. This change is accompanied by an increase in the number of people aged over 65 who come into contact with psychiatric services. The use of the Mental Health Act 1983 (MHA) in patients above 65 years of age is limited. These patients are less likely to appeal against their detention and may vary in sociodemographic and clinical characteristics compared with younger patients who are more likely to appeal against their detention. All patients detained for the first time under the MHA in the ten-year period 1992-2002 at Queen Elizabeth Psychiatric Hospital, Birmingham, were studied for socio-demographic and clinical characteristics. More appeals against detention came from people below 65 years of age. Patients detained on section 2 (MHA) appealed more often than patients on section 3. Only a few patients with a diagnosis of dementia appealed against their detention. Additional safeguards should be introduced for this group. We recommend that the appeal process should be simpler and should provide information in all the major languages used in the UK. | 18,754,213 |
Suicide pact by hanging: a case report. | A suicide pact is an agreement between two people to end their lives. The presence of an over-dependent relationship and a threat to the maintenance of closeness are strongly associated with the attempt. We present a case of a suicide pact where a 19-year-old female and a 20-year-old male who were lovers committed suicide by hanging because of opposition to their marriage from the family members. | 18,754,217 |
Family history of cardiovascular disease as a risk factor for coronary artery disease in adult offspring. | There is controversy about the role of positive family history as an independent risk factor for coronary artery disease. The aim of this work was to investigate the influence of family history on presentation of coronary artery disease in adult offspring, and on its severity. In a retrospective cross-sectional study at Tehran Heart Center (University of Tehran Medical Sciences), 6399 patients with established coronary artery disease who underwent coronary angiography for standard indications were assessed. Coronary artery disease was defined as atherosclerotic involvement of more than 50% in at least one major coronary artery. 953 patients (14.9%) had a verified positive family history of coronary artery disease, of whom 193 patients (20.2%) and 215 patients (22.5%) had paternal and maternal positive history, respectively. The mean age of clinical onset of ischemic heart disease in patients with a positive history was significantly lower than patients with no history (p < 0.001). Left main coronary lesion was significantly more frequent in patients with positive history (p = 0.017). Multivariate logistic regression analysis demonstrated that presentation of coronary artery disease in the form of acute coronary syndrome was significantly more prevalent in the background of positive family history (odds ratio, OR = 1.44, 95% confidence interval, CI: 1.14-1.83, p = 0.002), especially above 45 years old. These findings indicate that positive family history is a major risk factor for coronary artery disease which strongly predisposes to the atherosclerotic process at younger ages; therefore, these patients should be evaluated and managed more intensively for other risk factors. | 18,754,276 |
Maternal serum mannose-binding lectin in severe preeclampsia. | We aimed to investigate the level of serum mannose-binding lectin (MBL) in severe preeclamptic patients, women with uncomplicated pregnancies, and healthy reproductive-age females and its impact on gestational age at delivery and birth weight. Serum MBL levels were measured in 27 severe preeclampsia patients (Group 1), 27 patients with uncomplicated pregnancies (Group 2), and 25 healthy reproductive-age women (Group 3). The mean serum MBL was significantly higher (p < or = 0.05) in Group 1 than in Groups 2 and 3, while the levels in Groups 2 and 3 did not significantly differ. The mean gestational age at delivery and mean birth weight were significantly lower in Group 1. In Group 1, serum MBL was negatively correlated (p < or = 0.05) with the gestational age at delivery and birth weight. Serum MBL increased in preeclampsia and was negatively correlated with the gestational age at birth and birth weight, indicating an underlying immunopathogenesis. | 18,754,287 |
Mid-trimester maternal serum AFP levels in predicting adverse pregnancy outcome. | In this prospective study, we investigated the association between mid-trimester maternal serum alpha-fetoprotein AFP (MSAFP) levels and adverse pregnancy outcome in a South-Western Greek population. 110 healthy Greek women with spontaneous pregnancies, investigated for MSAFP levels between the 13th and 24th week of gestation and followed for adverse pregnancy outcome. AFP levels > 2.0 multiples of the median value for gestation were considered abnormal. Statistical analysis was performed by Pearson's chi-square test. Elevated MSAFP levels were detected in a total of 27 of the 110 women studied (24.5%). Among them, only four women (14.8%) developed pregnancy complications. Multiparameter testing of placental function in the mid-trimester (uterine artery Doppler, placental morphology and MSAFP screening) may allow us to identify women with increased risk of developing severe placental insufficiency and pregnancy complications. | 18,754,295 |
Placenta percreta presenting in the first trimester and resulting in severe consumption coagulopathy and hysterectomy: a case report. | Placenta percreta complicating pregnancy in the first trimester is extremely rare, and only a few cases have been reported in the literature. A patient with risk factors for placenta percreta that presented as first trimester fetal demise, unresponsive to medical management with prostaglandin, is presented. The patient required an emergency hysterectomy to control the bleeding after uterine curettage which was complicated by severe consumption coagulopathy. This rare entity can lead to significant mortality and morbidity, particularly in the background of an increased prevalence of the disease and its associated risk factors, and the large number of spontaneous and induced abortions performed worldwide. | 18,754,300 |
Successful treatment of advanced endometriosis with extremely high CA 125 and moderately elevated CA 15-3 levels. | We present the case of a patient with advanced endometriosis who presented with chronic pelvic pain, bilateral unruptured ovarian endometrioma, massive peritoneal implants and extremely elevated CA 125, and also elevated CA 15-3 levels. Laparoscopy revealed bilateral unruptured ovarian endometrioma and diffuse peritoneal endometriotic implants. Increased association of elevated levels of CA 125 and CA 15-3 is not so common in advanced endometriosis. The case was successfully treated with laparoscopy and combined low-dose oral contraceptive with one year of follow-up. To the best of our knowledge among the reported cases this is the highest CA 15-3 level ever reported with an extremely elevated CA 125 level. | 18,754,302 |
The selection and use of essential medicines. | This report presents the recommendations of the Subcommittee of the WHO Expert Committee responsible for the WHO Model List of Essential Medicines. The task of this Subcommittee was to draw up the first WHO Model List of Essential Medicines for Children. The first part of the report contains a summary of the Committee's considerations and justifications for the inclusion of particular medicines in the Model List for Children. Appendices to the main report include the first WHO Model List of Essential Medicines for Children, a list of all the items it contains sorted according to their 5-level Anatomical Therapeutic Chemical (ATC) classification codes and a summary of medicines to be reviewed before the next meeting of the Subcommittee. | 18,754,303 |
[Arguments against implementing a population-based screening programme for colorectal cancer]. | Screening healthy people at low risk of colorectal cancer using faecal occult blood testing (FOBT) is an old method that was proven effective in reducing colorectal cancer mortality in randomised controlled trials published in 1993-1996. Screening reduced colorectal cancer mortality by 1 per 10,000 person-years and increased colonoscopy rates by 50 per 10,000 person-years. Population screening increases the annual cost of the diagnosis and treatment of colorectal cancer by at least 35%. Physicians and other well-informed citizens rarely undergo colorectal cancer screening. In prioritising health care needs, preference should be given to the needs of actual patients, rather than placing demands on healthy individuals. | 18,754,310 |
[Transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005]. | To determine the number of reported cases of transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005 and to determine how many cases were associated with incompatibility between leukocyte-reactive antibodies in the donor plasma and leukocytes or antigens in the recipient. Retrospective national case review. Cases of TRALI reported in 2002-2005 were assessed according to the national clinical definition of TRALI, and the relationship between TRALI and transfusion was assessed. Additional clinical details were requested from the treating hospital as necessary. The results of leukocyte serological tests from donors and recipients were linked to clinical cases. For cases with positive leukocyte serological tests, the relevant blood components and the sex of the donor were recorded. Of the 46 cases reported, 6 had insufficient information. 8 cases did not meet the definition or had another more likely diagnosis. There was a trend toward an increase in the number of reports: 12 cases were reported in 2005, corresponding with 1:60,000 blood components. Of the 40 evaluable cases, 32 (80%) met the definition of TRALI and were deemed to be definitely (n = 16), probably (n = 5) or possibly (n = 11) related to transfusion. Severity ranged from moderate to life-threatening, and there was one TRALI-related death. Leukocyte serology was fully investigated in 18 cases: 13 (72%) had leukocyte incompatibility and in 5 cases exclusively fresh frozen plasma from a female donor was implicated. | 18,754,313 |
Analysis of children with Chlamydophila (Chlamydia) pneumoniae and Mycoplasma pneumoniae respiratoryinfections by real-time PCR assay and serological tests. | We examined 73 children with respiratory infections for Chlamydophila (Chlamydia) pneumoniae and Mycoplasma pneumoniae using real-time PCR assay and serological tests. C. pneumoniae and M. pneumoniae infections were found in 11 (15.1%) and 6 (8.2%) cases, respectively. The sensitivities and specificities of real-time PCR versus definite diagnosis of acute infection were 63.6% and 100% for C. pneumoniae, and 100% and 100% for M. pneumoniae, respectively. C. pneumoniae PCR-negative results appeared to be due to poor growth of the organism. The sensitivity and specificity of ImmunoCard tests were 33.3% and 82.1%, respectively, indicating that the efficacy of rapid diagnosis was disputable. The present results suggest that real-time PCR is suitable for rapid diagnosis as a first screening test to determine first-line antibacterial agents to be used against these infectious diseases. | 18,754,321 |
Evolution of human immunodeficiency virus type 1 serotypes in northern Tanzania: a retrospective study. | The HIV-1 epidemic in Tanzania is characterized by the circulation of heterogeneous virus subtypes. A retrospective study was conducted to determine the changing pattern of circulating HIV-1 subtypes in northern Tanzania. A peptide-binding enzyme immunoassay (PEIA) was employed to analyse 305 HIV-1 positive serum and plasma samples collected between 1985 and 2005. Samples were serotyped using synthetic peptides representing HIV-1 genotypes A-E derived from consensus gp120 V3 sequences. Plasma samples collected in 2005 were V3 genotyped for comparison with PEIA results. In 1985, serotypes A and D were co-circulating while serotype C was first detected in 1990. In 2001 and 2005, serotype C was the most prevalent, serotype A was stable, and serotype D was declining. PEIA is relatively rapid and simple to perform compared to molecular approaches, and is a valuable epidemiological tool in regions with limited resources. HIV-1 classification into serotypes based on antigenic V3 diversity may be a useful screening tool for the identification of HIV-1 variants with regard to diagnosis, treatment, disease progression and candidate vaccine development. | 18,754,325 |
Indoor levels of polycyclic aromatic hydrocarbons in homes with or without wood burning for heating. | The aim of this study was to investigate the impact of domestic wood burning on indoor levels of polycyclic aromatic hydrocarbons (PAHs). Indoor and outdoor concentrations of 27 PAHs were measured during wintertime in homes with (n= 13) or without (n 0) wood-burning appliances and at an ambient site in a Swedish residential area where wood burning for space heating is common. Twenty-four hour indoor levels of anthracene, benzo(ghi)fluoranthene, cyclopenta(cd)pyrene, benz(a)anthracene, chrysene/triphenylene, benzo(a)pyrene (BaP), indeno(1,2,3-cd)pyrene, benzo(ghi)perylene, and coronene were significantly (about 3- to 5-fold) higher in homes with, compared with homes without, wood-burning appliances. The outdoor levels of PAHs were generally higher than the indoor levelsfor all PAHs exceptforthe methylated phenanthrenes. The total PAH cancer potency (sum of BaP equivalents) was significantly higher (about 4 times) in the wood-burning homes compared with the reference homes, with BaP being the largest contributor, while phenanthrene made the largest contribution to the total PAH concentration in indoor and outdoor air. The median indoor BaP level in the wood-burning homes (0.52 ng/m3) was 5 times higher than the Swedish health-based guideline of 0.1 ng/m3, which was also exceeded outdoors on all days (median 0.37 ng/m3). | 18,754,350 |
Catalytic wet air oxidation of aniline with nanocasted Mn-Ce-oxide catalyst. | The catalytic wet air oxidation of aqueous solution containing 1000 ppm aniline was conducted in a trickle-bed reactor packed with a novel nanocasted Mn-Ce-oxide catalyst (surface area of 300 m2/g) prepared using SBA-15 silica as a hard template. A range of liquid hourly space velocities (5-20 h(-1)) and temperatures (110-140 degrees C) at 10 bar of oxygen were tested. The experiments were conducted to provide the intrinsic performance of the catalysts. Complete aniline conversion, 90% TOC conversion, and 80% nitrogen mineralization were achieved at 140 degrees C and 5 h(-1). Blank experiments yielded relatively low homogeneous aniline (<35%) and negligible TOC conversions. Fast deactivation of the catalysts was experienced due to leaching caused by complexation with aniline. Acidification of the solution with HCI (molar HCI to aniline ratio of 1.2) was necessary to avoid colloidization and leaching of the nanoparticulate catalyst components. The catalyst displayed stable performance for over 200 h on stream. | 18,754,364 |
Laboratory measurements of the heterogeneous oxidation of condensed-phase organic molecular makers for meat cooking emissions. | Multiphase oxidation of trace organic constituents inside of complex atmospheric particles is not well understood. In this study, organic aerosol formed from flash-vaporized residual grease from meat cooking was exposed to atmospherically relevant ozone concentrations in a smog chamber for 4-6 h. Changes in particle composition were measured to determine reaction rates for important molecular markers used for source apportionment analysis (oleic acid, palmitoleic acid, and cholesterol). Results are also presented for palmitic and stearic acids and likely reaction products. To quantify oxidation rates over a range of atmospheric conditions, separate experiments were conducted at low and high relative humidity and using particles mixed with and without secondary organic aerosol. Although particle composition, relative humidity, and secondary organic aerosol all influence the reaction rates, the unsaturated compounds were rapidly oxidized in every experiment. At typical summertime conditions, palmitoleic acid, oleic acid and cholesterol are estimated to have a chemical lifetime of about one day. The experimentally determined reaction rates are used in conjunction with the chemical mass balance model to investigate the effects of aging on source apportionment estimates. The results highlight that assumptions regarding the photochemical stability of molecular markers can lead to substantial biases in predictions of receptor models. | 18,754,366 |
Atmospheric transport and outflow of polycyclic aromatic hydrocarbons from China. | A potential receptor influence function (PRIF) model, based on air mass forward trajectory calculations, was applied to simulate the atmospheric transport and outflow of polycyclic aromatic hydrocarbons (PAHs) emitted from China. With a 10 day atmospheric transport time, most neighboring countries and regions, as well as remote regions, were influenced by PAH emissions from China. Of the total annual PAH emission of 114 Gg, 92.7% remained within the boundary of mainland China. The geographic distribution of PRIFs within China was similar to the geographic distribution of the source regions, with high values in the North China Plain, Sichuan Basin, Shanxi, and Guizhou province. The Tarim basin and Sichuan basin had unfavorable meteorological conditions for PAH outflow. Of the PAH outflow from China (8092 tons or 7.1% of the total annual PAH emission), approximately 69.9% (5655 tons) reached no further than the offshore environment of mainland China and the South China Sea. Approximate 227, 71, 746, and 131 tons PAHs reached North Korea, South Korea, Russia-Mongolia region, and Japan, respectively, 2-4 days after the emission. Only 1.4 tons PAHs reached North America after more than 9 days. Interannual variation in the eastward PAH outflow was positively correlated to cold episodes of El Niño/Southern Oscillation. However, trans-Pacific atmospheric transport of PAHs from China was correlated to Pacific North America index (PNA) which is associated with the strength and position of westerly winds. | 18,754,369 |
Quantitative structure-property relationships for predicting metal binding by organic ligands. | Quantitative structure-property relationships (QSPRs) are developed to predict the complexation of Al(III), Ca(II), Cd(II), Cu(II), Ni(II), Pb(II), and Zn(II) by organic ligands containing carboxylate, phenol, amine, ether, and alcoholfunctional groups. These QSPRs predict conditional stability constants (K(M') at pH 7.0 and I = 0.1) over a range of ligand types with consistent uncertainties of approximately 1 log unit without requiring any steric or connectivity information. Calibration and validation data sets were constructed using 1:1 complex formation constants from the NIST Critical Stability Constants database (version 8.0). The descriptor variables are intuitive quantities conceptually related to metal binding, such as the numbers of various ligand groups, charge density, etc. The resulting calibrations have r2 = 0.87 to 0.93 and Spred = 0.67 to 1.05 log units, with positive values for all ligand count descriptor variables. The QSPRs account for 75-95% of the variability in the validation data set with RMSE of 0.74 to 1.30 log units. These QSPRs improve upon previous work by providing a tested and mechanistically reasonable method for log K(M') prediction with uncertainties comparable to or betterthan other QSPRs calibrated with groups of diverse ligands. | 18,754,371 |
Quantification of functional groups and modeling of their ionization behavior in the active layer of FT30 reverse osmosis membrane. | A new experimental approach was developed to measure the concentration of charged functional groups (FGs) in the active layer of thin-film composite reverse osmosis (RO) and nanofiltration (NF) membranes as a function of solution pH. FT30 RO membrane, with a fully aromatic polyamide (PA) active layer sandwiched between a polysulfone support and a coating layer, was used. The experiments consisted of saturating charged FGs with heavy ion probes, and determining the ion probe concentration by Rutherford backscattering spectrometry (RBS). Deprotonated carboxylic groups were saturated with Ag+, and protonated amine groups with W04(2-). The ionization behavior of carboxylic and amine groups was modeled based on acid-base equilibrium theory. While the ionization behavior of amine groups was satisfactorily described by one dissociation constant (pKa = 4.74), two pKa values (5.23 and 8.97) were necessary to describe the titration curve of carboxylic groups. These results were consistent with the bimodal pore size distribution (PSD) of FT30 active layer reported in the literature. The calculated total concentrations of carboxylic and amine groups in the active layer of the FT30 RO membrane studied were 0.432 and 0.036 M, respectively, and the isoelectric point (IEP) was 4.7. The total concentration of carboxylic and amine groups revealed that the degree of cross-linking of the PA active layer of the FT30 RO membrane studied was 94%. | 18,754,378 |
Transformation of oxidation products and reduction of estrogenic activity of 17beta-estradiol by a heterogeneous photo-Fenton reaction. | A novel photo-Fenton catalyst, alpha-FeOOH loaded resin (alpha-FeOO HR), was synthesized and evaluated through transformation of a steroidal endocrine disrupting compounds (EDC), 17beta-estradiol (E2), under weak UV irradiation in the presence of H2O2. E2 photodegradation intermediates elucidated in detail by GC/MS and LC/MS/MS analyses and detailed reaction pathways are proposed. A yeast-based estrogen screen for E2 and its photodegradation intermediates was performed to measure the reduction of estrogenic activity in different water matrices during the heterogeneous photo-Fenton process. The results showed that alpha-FeOOHR not only degraded E2 but also removed the estrogenic activity originating from E2, its degradation intermediates, and its products. However, the water matrix present in drinking water may impactestrogenic activity reduction. The results are important to evaluate the ability of photo-Fenton advanced oxidation processes in reducing EDCs and their associated estrogenicity from drinking water. | 18,754,381 |
Development of silica/vanadia/titania catalysts for removal of elemental mercury from coal-combustion flue gas. | SiO2/V2O5/TiO2 catalysts were synthesized for removing elemental mercury (Hg0) from simulated coal-combustion flue gas. Experiments were carried out in fixed-bed reactors using both pellet and powder catalysts. In contrast to the SiO2-TiO2 composites developed in previous studies, the V2O5 based catalysts do not need ultraviolet light activation and have higher Hg0 oxidation efficiencies. For Hg0 removal by SiO2-V2O5 catalysts, the optimal V2O5 loading was found between 5 and 8%, which may correspond to a maximum coverage of polymeric vanadates on the catalyst surface. Hg0 oxidation follows an Eley-Rideal mechanism where HCI, NO, and NO2 are first adsorbed on the V2O5 active sites and then react with gas-phase Hg0. HCI, NO, and NO2 promote Hg oxidation, while SO2 has an insignificant effect and water vapor inhibits Hgo oxidation. The SiO2-TiO2-V2O5 catalysts exhibit greater Hg0 oxidation efficiencies than SiO2-V2O5, may be because the V-O-Ti bonds are more active than the V-O-Si bonds. This superior oxidation capability is advantageous to power plants equipped with wet-scrubbers where oxidized Hg can be easily captured. The findings in this work revealed the importance of optimizing the composition and microstructures of SCR (selective catalytic reduction) catalysts for Hg0 oxidation in coal-combustion flue gas. | 18,754,385 |
Bleedings, purges, and vomits: Dr. Benjamin Rush's republican medicine, the bilious remitting yellow-fever epidemic of 1793, and the non-origin of the law of informed consent. | To the consternation of many physicians, the modern law of informed consent imposes certain constraints on their actions, not least that they respect patients' decisions to redefine at will the scope of care. The consequences of this transfer of power are often a nuisance and occasionally fatal, but always a reflection of democracy's leveling march: Physicians now take orders rather than give them. However frustrating the modern preference for process over result might be, we should ask ourselves-before condemning the law's evolution-about the consequences for patients' health of a more radically democratic practice of medicine. This paper proposes to examine this question as framed by the life of Dr. Benjamin Rush, who, in addition to signing the Declaration of Independence, crafted a medical practice uniquely suited to the young Republic's presumed moral character: Self-aware sufferers would promptly identify their own maladies and courageously treat themselves. In the end, his enterprise was flawed because his democratic instincts misled not only his scientific inquiries (disease is complex, not simple) but also his practice recommendations (patients are scared, not intrepid). Reflection on Rush's failed project should give pause to those who lament the passing of paternalistic medicine, for the law's requirements, however onerous they might be, tolerably accommodate both patients' need for physicians' expertise and our democratic belief that consent is the fundamental precondition of all rule. | 18,754,398 |
[Endothelial function assessment by positron emission tomography in patients with hypercholesterolemia]. | Hypercholesterolemia prompts to endothelial dysfunction (ED) and ED predisposes to atherogenesis. ED appears early in the course of atherogenesis and it is considered a coronary artery disease (CAD) marker. To assess endothelial function (EF) using Positron Emission Tomography (PET) in asymptomatic patients with recent dyslipidemia diagnosis and without history of ischemic heart disease and previous hypolipemiant treatment. Fourteen asymptomatic patients with recent dyslipidemia diagnosis (< 6 months) were studied by obtaining a lipid profile, blood glucose, and a three phase 13N-ammonia PET scan: rest, cold pressor test (CPT) and pharmacologic stress with adenosine. EF was assessed by calculating the coronary flow reserve (CFR), endothelial-dependant vasodilatation index (EDVI), and coronary blood flow increase percentage in CPT (% Delta CF). 79% of patients with dyslipidemia had ED and all their values were lower than those previously published as normal: rest coronary flow 0.44 +/- 0.12 vs 0.57 +/- 0.147 (p = 0.002), CPT coronary flow 0.57 +/- 0.17 vs 0.88 +/- 0.26 (p = 0.001), stress coronary flow 1.24 +/- 0.05 vs 1.81 +/- 0.35 (p = 0.005), EDVI 1.28 +/- 0.25 vs 1.53 +/- 0.24 (p 0.017), CRF 2.79 +/- 0.94 vs 3.15 +/- 0.48 (p 0.198) and % Delta CF 29.08 +/- 24.62% vs 53 +/- 24.60% (p 0.022). Asymptomatic patients in early stages of dyslipidemia showed a greater ED prevalence that was detected by 13N-ammonia PET scan. | 18,754,405 |
[Accuracy of 64 slice computed tomography angiography in the diagnosis of ischemic coronary artery disease]. | Multislice computed tomography coronary angiography (MSCT-CA) has been developed in the last years. One of the advantages is to supply information of the lumen and wall of the vessels. The aim was to assess the diagnostic accuracy of MSCT - CA to detect significant coronary stenoses taking as gold standard the invasive coronary angiography (ICA). We studied, after informed consent, 64 consecutive patients (50 males). First MSCT - CA was performed and afterwards with a media of 45 days the ICA. Sensitivity (SENS), specificity (ESP), positive predictive value (PPV), negative predictive value (NPV) and predictive precision (PP) were assessed per patients, per arteries and per segments. The SENS, ESP, PPV, PNV and PP were 96.4, 91.2, 87, 96.8, 93.5% respectively per patients and 95.7, 97, 88.2, 98.9, 96.7% respectively per arteries and 91, 99, 89, 99.6, 98.7% respectively per segments. The diagnostic accuracy decreased in patients with heart rate higher than 65 beats per minute, as well as in patients with calcium scoring higher than 400 Agatston Units or body mass index with or higher than 30 kg/m2 CS. Our results suggest that MSCT - CA has a good accuracy, especially in the ESP and NPV for the diagnosis of significant coronary stenoses in selected patients with calcium scoring of 400 Agatston Units or lower, heart rate with 65 beats per minute or lower with regular rhythm and body mass index lower than 30 kg/m2 CS. | 18,754,407 |
[Medical image retrieval based on low level feature fusion and relevance feedback]. | Based on chest images' features, this paper presents a retrieval method with domination color of partition, gray level co-occurrence matrix and gradient image shape invariant moments, as well as the fusion of them and the technique of relevance feedback. In Windows Vista environment with Visual C + +, a chest image retrieval prototype is implemented and the experiments have proved that this method has a better retrieval effect. | 18,754,416 |
[Multi-points pulse information acquisition and 3-D reconstruction based on grid-net images]. | A method of acquiring radial pulse information from the grid-net area on every pulse image frame is proposed based on the principle of lens imaging and the characteristics of image data. The radial pulse image data are collected by the pulse image sensor. Multi-points out-of-plane displacements of the pulse are acquired by the method. And the membrane surfaces are reconstructed, then the 3D information of the pulse can be observable. | 18,754,418 |
[Design of a flyback switch mode power supply for multichannel electrophysiological stimulators]. | In order to supply the multichannel electrical stimulator, a DC-DC flyback switch mode power supply based on a high-performance current mode controller UC3845 has been designed. The experimental results indicate that the power supply has satisfied the demands and can supply the multichannel electrical stimulator and similar apparatuses. | 18,754,421 |
[Identification of two potential serum biomarkers for ovarian cancer and clinical validation thereof]. | To identify practical biomarkers used in diagnosis of ovarian cancer. Peripheral blood samples were collected from 59 ovarian cancer patients, 64 ovarian benign tumors patients, and 142 healthy women and underwent column chromatography to purify the target proteins. The proteins thus obtained were identified with matrix-assisted desorption ionization tissue-of-flight mass spectrometry (MALDI-TOF MS). Immunohistochemistry was used to detect the expression of CCL18 and CXCL1 in the cancer tissues. ELISA was used to detect the serum CC118 and CXCL1 contents. Receiver operating characteristic curve was drawn to examine the sensitivity and specificity of the potential biomarker to ovarian cancer. The m/z 7,784 and 7,837 proteins were identified as chemokine CC2 motif ligand 18 (CCL18) and CXC Chemokines ligand 1 (CXCL1) respectively. The serum levels of CCL18 and CXCL1 of the patients with ovarian cancer were 150 +/- 62 ng/ml and 1 +/- 0.4 ng/ml respectively, both were significantly higher than those of the healthy control women and the patients with ovarian benign diseases (all P < 0.05). The diagnostic sensitivity and specificity of CXCL1 to ovarian cancer were 100% and 97.8% respectively. The diagnostic sensitivity of CCL18 was 100% to ovarian cancer of stages I-II and 86.1% to ovarian cancer of stages III-IV. The CCL18 positive rate in the cancer tissue was 84.6% and the CXCL1 expression rate was 96.2%. The model established based the combination of both biomarkers had the sensitivity and specificity to ovarian cancer of both 100%. CCL18 and CXCL1 may be used in early screening of ovarian cancer. | 18,754,431 |
Occurrence of zearalenone on Fusarium graminearum infected wheat and maize fields in crop organs, soil, and drainage water. | The mycotoxin zearalenone (ZON) is a very potent natural endocrine disrupting chemical, produced by Fusarium graminearum fungi growing on crops such as wheat and maize. Although it is well-investigated in food and feed, very little is known about its environmental fate and behavior. Here, we report the occurrence of ZON on F. graminearum infected wheat and maize fields in crop organs and soil and its emission via drainage water. ZON amounts in the investigated crops and topsoil were between 6.1 and 25.0 and up to 5.6 g/ha, respectively. ZON concentrations in drainage water were in the low nanogram per liter range with a maximum of 35 ng/ L. Cumulated ZON amounts emitted via drainage water ranged from 0.1 to 4.3 mg/ha, depending on the crop cultivated in the respective period. This corresponds to fractions between 0.001 and 0.070% of the initially present ZON amount in the plants. Because of the low concentrations emitted via drainage water, it can be assumed that ZON contributes little if at all to the overall estrogenicity of major surface water bodies. However, in small creeks, mainly fed by agricultural runoff, ZON might be present in environmentally critical concentrations at times of F. graminearum infections. | 18,754,460 |
Detailed characterization and profiles of crankcase and diesel particulate matter exhaust emissions using speciated organics. | A monitoring campaign was conducted in August-September 2005 to compare different experimental approaches quantifying school bus self-pollution. As part of this monitoring campaign, a detailed characterization of PM2.5 diesel engine emissions from the tailpipe and crankcase emissions from the road draft tubes was performed. To distinguish between tailpipe and crankcase vent emissions, a deuterated alkane, n-hexatriacontane-d74 (n-C36D74) was added to the engine oil to serve as an intentional quantitative tracer for lubricating oil PM emissions. This paper focuses on the detailed chemical speciation of crankcase and tailpipe PM emissions from two school buses used in this study. We found that organic carbon emission rates were generally higher from the crankcase than from the tailpipe for these two school buses, while elemental carbon contributed significantly only in the tailpipe emissions. The n-C36D74 that was added to the engine oil was emitted at higher rates from the crankcase than the tailpipe. Tracers of engine oil (hopanes and steranes) were present in much higher proportion in crankcase emissions. Particle-associated PAH emission rates were generally very low (< 1 microg/km), but more PAH species were present in crankcase than in tailpipe emissions. The speciation of samples collected in the bus cabins was consistent with most of the bus self-pollution originating from crankcase emissions. | 18,754,490 |
Permanganate oxidation of sulfur compounds to prevent poisoning of Pd catalysts in water treatment processes. | The practical application of Pd-catalyzed water treatment processes is impeded by catalyst poisoning by reduced sulfur compounds (RSCs). In this study, the potential of permanganate as a selective oxidant for the removal of microbially generated RSCs in water and as a regeneration agent for S-poisoned catalysts was evaluated. Hydrodechlorination using Pd/Al2O3 was carried out as a probe reaction in permanganate-pretreated water. The activity of the Pd catalysts in the successfully pretreated reaction medium was similar to that in deionized water. The catalyst showed no deactivation behavior in the presence of permanganate at a concentration level < or = 0.07 mM. With a residual oxidant concentration of > or = 0.08 mM, a significant but temporary inhibition of the catalytic dechlorination was observed. Unprotected Pd/Al2O3, which had been completely poisoned by sulfide, was reactivated by a combined treatment with permanganate and hydrazine. However, the anthropogenic water pollutants thiophene and carbon disulfide were resistant against permanganate. Together with the preoxidation of catalyst poisons, hydrophobic protection of the catalysts was studied. Pd/zeolite and various hydrophobically coated catalysts showed a higher stability against ionic poisons and permanganate than the uncoated catalyst. By means of a combination of oxidative water pretreatment and hydrophobic catalyst protection, we provide a new tool to harness the potential of Pd-catalyzed hydrodehalogenation for the treatment of real waters. | 18,754,501 |
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