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Total synthesis of neurymenolide A based on a gold-catalyzed synthesis of 4-hydroxy-2-pyrones.
Treat me gently: for a selective synthesis of the unusually sensitive cyclophanic α-pyrone neurymenolide A, the chosen catalysts must be able to distinguish between six different sites of unsaturation, without scrambling any of the skipped π systems. This challenge was met with a new gold-catalyzed pyrone synthesis in combination with a molybdenum-catalyzed ring-closing alkyne metathesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Estrogen and mu-opioid receptor antagonists counteract the 17 beta-estradiol-induced licking increase and interferon-gamma reduction occurring during the formalin test in male rats.
Women have a higher incidence of chronic pain syndromes than men and are generally more sensitive to experimental pain. Numerous studies have shown that the female gonadal hormones, estrogens, can profoundly affect the nervous and immune systems, including mechanisms involved in pain and nociception. In the present study, we used antagonists of estrogen receptors (ER) or mu-opioid receptors (mu OR) to evaluate the effects of estrogens on formalin-induced behavioural and immune responses in male rats. After two days of priming with 17 beta-estradiol or saline (i.c.v.), animals were subjected to the formalin test; 15 min prior to formalin (50 microl, 5%) or sham injection in the hind paw, animals were treated with an ER antagonist (ICI 182,780, ICI) or a mu OR antagonist (beta-funaltrexamine, FNA) or saline. The spontaneous behaviours, pain-related behaviours and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells were studied in all groups. We found that central administration of estradiol increased the amount of licking of the formalin-injected paw in the second phase of the formalin test. Whereas ICI and FNA had no effect on pain behaviour in saline-pre-treated animals, both antagonists reversed the estradiol-induced increase in licking. The immune system was differently affected by formalin and estradiol treatment. Indeed, formalin injection per se decreased IFN-gamma production; estradiol had no effect on sham-injected animals but strongly reduce the decrease of IFN-gamma production in formalin-injected animals. The results demonstrate that centrally acting estrogens affect ER- and mu OR-mediated pain processing and influence immune function. | {
"pile_set_name": "PubMed Abstracts"
} |
Ab initio molecular dynamics simulations of the initial stages of solid-electrolyte interphase formation on lithium ion battery graphitic anodes.
The decomposition of ethylene carbonate (EC) during the initial growth of solid-electrolyte interphase (SEI) films at the solvent-graphitic anode interface is critical to lithium ion battery operations. Ab initio molecular dynamics simulations of explicit liquid EC/graphite interfaces are conducted to study these electrochemical reactions. We show that carbon edge terminations are crucial at this stage, and that achievable experimental conditions can lead to surprisingly fast EC breakdown mechanisms, yielding decomposition products seen in experiments but not previously predicted. | {
"pile_set_name": "PubMed Abstracts"
} |
Redistribution and increase in cortical inositol 1,4,5-trisphosphate receptors after meiotic maturation of the mouse oocyte.
Mouse oocytes develop sensitivity to inositol 1,4,5-trisphosphate (IP3) during oocyte maturation. We recently reported that a change in the organization of the endoplasmic reticulum (ER) during oocyte maturation may contribute to this enhanced sensitivity (Mehlmann et al., 1995, Dev. Biol. 170, 607-615). Here, we investigated whether there is an increase in the number of available IP3 receptors after maturation and whether there is a redistribution of IP3 receptors similar to the redistribution of the ER that occurs during maturation. Western blot analysis of the IP3 receptor in oocytes and eggs demonstrated a 1.8-fold increase in immunoreactive mass of the IP3 receptor following oocyte maturation. Microinjection of the function-blocking monoclonal antibody 18A10 inhibited IP3-induced Ca2+ release in a concentration-dependent manner in both eggs and oocytes. More antibody was required to inhibit Ca2+ release to the same extent in eggs compared to oocytes when both were injected with the same concentration of IP3, suggesting that eggs contain a greater number of functional IP3 receptors. Immunolocalization of the IP3 receptor revealed that receptors were present in large clusters, 1-2 microm in diameter, in the cortex of the mature egg except in a ring-shaped band of cortex adjacent to the meiotic spindle. In contrast, receptor clusters were located around the entire cortex of the immature oocyte and were much smaller (<1 microm); larger patches were sometimes seen, but they did not display the same spherical organization as those in eggs. These results suggest that the number of cortical IP3 receptors increases during mouse oocyte maturation and that this increase may contribute to enhanced Ca2+ release at fertilization. | {
"pile_set_name": "PubMed Abstracts"
} |
The pupil: a window on social automatic processing in autism spectrum disorder children.
Faces are crucial social stimuli, eliciting automatic processing associated with increased physiological arousal in observers. The level of arousal can be indexed by pupil diameter (the 'Event-Related Pupil Dilation', ERPD). However, many parameters could influence the arousal evoked by a face and its social saliency (e.g. virtual vs. real, neutral vs. emotional, static vs. dynamic). A few studies have shown an atypical ERPD in autism spectrum disorder (ASD) patients using several kinds of faces but no study has focused on identifying which parameter of the stimulus is the most interfering with face processing in ASD. In order to disentangle the influence of these parameters, we propose an original paradigm including stimuli along an ecological social saliency gradient: from static objects to virtual faces to dynamic emotional faces. This strategy was applied to 186 children (78 ASD and 108 typically developing (TD) children) in two pupillometric studies (22 ASD and 47 TD children in the study 1 and 56 ASD and 61 TD children in the study 2). Strikingly, the ERPD in ASD children is insensitive to any of the parameters tested: the ERPD was similar for objects, static faces or dynamic faces. On the opposite, the ERPD in TD children is sensitive to all the parameters tested: the humanoid, biological, dynamic and emotional quality of the stimuli. Moreover, ERPD had a good discriminative power between ASD and TD children: ASD had a larger ERPD than TD in response to virtual faces, while TD had a larger ERPD than ASD for dynamic faces. This novel approach evidences an abnormal physiological adjustment to socially relevant stimuli in ASD. | {
"pile_set_name": "PubMed Abstracts"
} |
Zinc-Catalyzed Alkyne-Carbonyl Metathesis of Ynamides with Isatins: Stereoselective Access to Fully Substituted Alkenes.
A zinc-catalyzed intermolecular alkyne-carbonyl metathesis reaction of ynamides with isatins followed by an amide to ester conversion has been developed, which produces the indolone derivatives with a fully substituted alkene species in good to high yields. The salient features of this reaction include the following: mild reaction conditions, an inexpensive zinc catalyst, a broad substrate scope, the excellent regiocontrol and stereoselectivity, and amenable to the gram scale. | {
"pile_set_name": "PubMed Abstracts"
} |
Glutathione transferase modulates acute ethanol-induced sedation in Drosophila neurones.
Heavy alcohol consumption leads to neuropathological damage and alcohol use disorder, which affects the health of people and results in a cost burden. However, the genes modulating sensitivity to ethanol remain largely unknown. Here, we identified a novel gene, Drosophila glutathione transferase omega 1 (GstO1), which plays a critical role in regulating sensitivity to ethanol sedation. GstO1 mutant flies showed highly increased ethanol sensitivity. Furthermore, the expression level of GstO1 regulates the behavioural response to ethanol, because decreasing and increasing GstO1 affects sedation sensitivity in a contrasting manner. In addition, the RNA interference-mediated knockdown of GstO1 expression reveals that GstO1 mediates sensitivity to ethanol sedation in neurones, including dopaminergic and serotonergic neurones. Altogether, our findings provide the first evidence for the involvement of glutathione transferase in the response to alcohol in Drosophila and provide a novel mechanistic insight into the toxicity and sensitivity of ethanol exposure. | {
"pile_set_name": "PubMed Abstracts"
} |
International Commission on Trichinellosis: recommendations on the use of serological tests for the detection of Trichinella infection in animals and man.
The use of serological tests to detect Trichinella infection in domestic and wild animals and in humans has not been standardised yet. This review provides an uniform set of recommendations for the development and use of serological tests to detect circulating antibodies in serum samples. The recommendations are based on the best scientific published information and on the unpublished data from laboratories with a great expertise in this field and represent the official position of the International Commission on Trichinellosis regarding acceptable methods and the evaluation of the sensitivity and specificity. These recommendations are subject to change as new scientific information becomes available. | {
"pile_set_name": "PubMed Abstracts"
} |
A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.
Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.). | {
"pile_set_name": "PubMed Abstracts"
} |
Follow-up of radiologically totally implanted central venous access ports of the upper arm: long-term complications in 127,750 catheter-days.
The purpose of this article is to retrospectively evaluate radiologically totally implanted central venous access ports (VAPs) of the upper arm in terms of safety, technical feasibility, and device-related complications. Five hundred seven consecutive patients (mean [± SD] age, 59.2 ± 11.4 years) who received a totally implanted central VAP between January 2005 and July 2010 were included. The insertion procedure was performed in an interventional radiology suite using the Seldinger technique. Neither antibiotic prophylaxis nor long-term anticoagulation was administered. In 507 patients, a total of 523 devices were implanted. Of these 523 procedures, 512 complete datasets were available during follow-up. The primary technical success rate was 99.04%. All procedures were completed without major complications. During follow-up and with a total number of 127,750 days of totally implanted central VAP implantation (248 ± 279 days/patient; range, 1-1687 days/patient), 50 devices had to be revised because of complications (9.8%). Complications occurred at a mean of 114 ± 183 days (range, 1-1113 days) after placement. Early complications were noted in 21 of 512 cases (4.1%), and late complications were noted in 29 of 512 cases (5.7%). Complications were as follows: local infections, 4.9% (25/512); systemic infections, 0.4% (2/512); venous thrombosis, 1.6% (8/512); paralysis of the median nerve, 0.6% (3/512); skin dehiscence at the port site, 0.2% (1/512); and mechanical problems including catheter line displacement, port hub rotation, and catheter fracture, 2.1% (11/512). Radiologic placement of a totally implanted central VAP is a safe procedure with a low rate of both early and late device-related complications. The method is effective for delivery of chemotherapy, parenteral nutrition, and frequent IV medication. | {
"pile_set_name": "PubMed Abstracts"
} |
Biofilters for stormwater harvesting: understanding the treatment performance of key metals that pose a risk for water use.
A large-scale stormwater biofilter column study was conducted to evaluate the impact of design configurations and operating conditions on metal removal for stormwater harvesting and protection of aquatic ecosystems. The following factors were tested over 8 months of operation: vegetation selection (plant species), filter media type, filter media depth, inflow volume (loading rate), and inflow pollutant concentrations. Operational time was also integrated to evaluate treatment performance over time. Vegetation and filter type were found to be significant factors for treatment of metals. A larger filter media depth resulted in increased outflow concentrations of iron, aluminum, chromium, zinc, and lead, likely due to leaching and mobilization of metals within the media. Treatment of all metals except aluminum and iron was generally satisfactory with respect to drinking water quality standards, while all metals met standards for irrigation. However, it was shown that biofilters could be optimized for removal of iron to meet the required drinking water standards. Biofilters were generally shown to be resilient to variations in operating conditions and demonstrated satisfactory removal of metals for stormwater-harvesting purposes. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparative studies of regional CNS blood flow and evoked potentials in the cat. Effects of hypotensive ischemia on somatosensory evoked potentials in cerebral cortex and spinal cord.
Functional resistance to graded hypotensive ischemia of various segments of the somatosensory pathway was determined in anesthetized cats by repeated concurrent recordings of regional blood flow measured by hydrogen clearance, and evoked potentials (EPs), of dorsal horn of lumbar spinal cord and cerebral cortex. During normal resting CNS blood flow (CBF), there were significant successive reductions of EP amplitudes, recorded from presynaptic spinal components (634, 424-949 microV; re-linearized mean and 95% confidence limits of log-transformed data) compared to postsynaptic spinal (359, 247-522 microV) and presynaptic cortical (50, 32-79 microV) and to postsynaptic cortical components (33, 22-50 microV). During ischemia amplitudes of EPs in spinal cord and cerebral cortex showed significantly different behaviors. The presynaptic spinal component was virtually independent of regional blood flow down to 12 percent of resting values, the postsynaptic cortical component exhibited strongest positive correlations (r = 0.45) with flow. In both regions postsynaptic amplitude was more sensitive to flow changes than respective presynaptic amplitudes. Despite similar regression coefficients for intermediate segments of somatosensory pathway, only postsynaptic spinal components were significantly correlated (r = 0.40) with regional flow. Presynaptic cortical amplitudes were variable and no significant flow dependence was demonstrated. Results suggested that in comparable degrees of regional ischemia of CNS functional integrity is determined by numbers of synaptic transmissions involved locally. Comparatively simple structures, e.g. the spinal cord, are less susceptible to ischemia and complex neuronal networks, e.g. the cerebral cortex, are more susceptible. | {
"pile_set_name": "PubMed Abstracts"
} |
From authorship to contributorship. Promoting integrity in research publication.
Shared authorship in nursing research presents practical and ethical dilemmas and does not effectively capture individual research participation and accountability. This study, which defined author contributions and practices in multiauthored nursing research, contributed to a better understanding of contemporary author participation and the inherent challenges faced by nurse scholars in determining authorship credit. A method of "contributorship" is proposed which would delineate individual contributions to the research project while maintaining professional integrity, scientific accountability, and scholarly recognition. | {
"pile_set_name": "PubMed Abstracts"
} |
Prognostic value of a positive-to-negative change in hormone receptor status after neoadjuvant chemotherapy in patients with hormone receptor-positive breast cancer.
To investigate the prognostic value of positive-to-negative changes in hormone receptor (HR) status after neoadjuvant chemotherapy (NCT) in patients with HR-positive breast cancer. Data from 224 stage II-III breast cancer patients with positive HR status before NCT who had residual disease in the breast after NCT were collected. HR status of the residual tumors was retested after NCT. A survival analysis was performed in 214 patients with adjuvant endocrine therapy regardless of post-NCT HR status. The survival analysis also examined other clinical and pathologic variables. In total, 15.2 % of patients had a positive-to-negative change in HR status after NCT, and this change was observed more frequently in HER-2-positive tumors than HER-2-negative tumors (P = 0.001). In 214 patients who had been treated with adjuvant endocrine therapy regardless of post-NCT HR status, the alteration in HR status was an independent factor for the prediction of a poorer disease-free survival (P = 0.026) and overall survival (P < 0.001) in the adjuvant endocrine therapy patients. The 5-year disease-free survival and overall survival rates were 43.5 % and 59.8 %, respectively, in patients with HR status conversion and 67.8 % and 82.5 %, respectively, in patients whose HR status remained positive (log rank test P = 0.003 and P = 0.001). The switch of HR status after NCT is remarkable for HR-positive tumors. An HR-negative switch may identify patients who would benefit from alternative systemic therapies. | {
"pile_set_name": "PubMed Abstracts"
} |
Exposure to mutagenic aromatic hydrocarbons of workers creosoting wood.
Creosote P1 is mutagenic in the Salmonella microsome assay towards strains TA1537, TA1538, TA98 and TA100 in the presence of S9 mix. The mutagenic polycyclic aromatic hydrocarbons benzo[a]pyrene and benz[a]anthracene in this mixture are detected in concentrations of 0.18 and 1.1%, respectively. Spot samples taken from contaminated surfaces in several areas of a wood-preserving industry were tested for mutagenicity. The positive results suggest that a wipe test can give a first indication of occupational exposure to mutagenic substances, particularly when greater exposure occurs via skin contact than via inhalation. In urine of rats, mutagens appeared after treatment with creosote. However, no increase in mutagenicity could be detected in urine of creosote workers in relation to their work. | {
"pile_set_name": "PubMed Abstracts"
} |
Cathodoluminescence in transmission electron microscopy.
We describe a cathodoluminescence spectrometer that is attached to an analytical transmission electron microscope. After a brief consideration of the set-up and the peculiarities of recording spectra and of mapping defect distributions in panchromatic and monochromatic cathodoluminescence, we discuss two examples of applications. Emphasis is placed on the potential for obtaining novel information about materials and processes on a microscopic and a nanoscopic scale by combining cathodoluminescence with the structural and chemical information for the same site of the specimen. We select an example concerning the role of In distribution in light emission from InGa/GaN quantum wells and a second one concerning the analysis of the initial electron radiation damage of Cu(In,Ga)Se(2) photovoltaic films. | {
"pile_set_name": "PubMed Abstracts"
} |
Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid.
The results of infrared spectroscopic investigations into the band assignments, vibrational relaxation, and solvation dynamics of the common anti-tuberculosis treatment Isoniazid (INH) are reported. INH is known to inhibit InhA, a 2-trans-enoyl-acyl carrier protein reductase enzyme responsible for the maintenance of cell walls in Mycobacterium tuberculosis but as new drug-resistant strains of the bacterium appear, next-generation therapeutics will be essential to combat the rise of the disease. Small molecules such as INH offer the potential for use as a biomolecular marker through which ultrafast multidimensional spectroscopies can probe drug binding and so inform design strategies but a complete characterization of the spectroscopy and dynamics of INH in solution is required to inform such activity. Infrared absorption spectroscopy, in combination with density functional theory calculations, is used to assign the vibrational modes of INH in the 1400-1700 cm(-1) region of the infrared spectrum while ultrafast multidimensional spectroscopy measurements determine the vibrational relaxation dynamics and the effects of solvation via spectral diffusion of the carbonyl stretching vibrational mode. These results are discussed in the context of previous linear spectroscopy studies on solid-phase INH and its usefulness as a biomolecular probe. | {
"pile_set_name": "PubMed Abstracts"
} |
Low-loss all-fiber acousto-optic tunable filter.
We report significant advances in the development of simple all-fiber, tunable acousto-optic spectral filters based on null couplers. The performance agrees well with theoretical predictions and is attributed to improved control of the coupler uniformity. Furthermore, using a double-pass arrangement, we demonstrate filter bandwidth reduction and improved sidelobe suppression of -20 dB . The double-pass configuration is also shown to double the frequency shifts that are obtainable from such devices. | {
"pile_set_name": "PubMed Abstracts"
} |
Integrin targeted drug and gene delivery.
Recently, there has been substantial progress in the development of integrin targeted pharmaceuticals and drug delivery systems. Integrin is an important member in the cell adhesion molecule family, which is involved in regulation of complex biological conditions, from keeping normal physiological activities to causing cellular dysfunction in diseased cells. Hence, it is timely to summarize the recent developments in integrin targeted drug and gene delivery systems to understand better their advantages and limitations. In this review, advances in the discovery and clinical trials of these integrin antagonists against different integrin subunits are summarized and discussed. Besides using integrin inhibitor as a single therapeutic agent, integrin antagonists that were conjugated to cytotoxic drugs by synthetic chemistry or coupled to biomacromolecules by either DNA recombination technology or fusion protein technology for integrin targeted therapy have been explored. Furthermore, nanoparticles with integrin targeting ligands for both drug and gene delivery, typically for antiangiogenesis and anticancer therapy, are highlighted and evaluated. This review sheds light on the future development of integrin targeted drug and/or gene delivery systems. Although thus far there are still limitations, integrin targeted delivery systems have already shown their potential as important pharmaceuticals in the near future. | {
"pile_set_name": "PubMed Abstracts"
} |
[Possible role of 06-methylguanine-DNA-transferase in the response of patients with primary tumor of the brain to chemotherapy using chloro-ethyl-nitroso-urea: results of a current study].
We have started a study to measure the MT activity in surgical specimens from high grade human malignant gliomas, with the dual aim to (i), know whether lack of activity can be demonstrated in these tumors, and (ii), relate the measured levels of MT to the histology of the tumors and to the response of patients to chemotherapy with 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU). To date, 12 Gliomas have been assayed. In 11 tumors, MT activities ranging from 30 to 150 fmoles/mg protein have been measured. The only negative specimen derived from a patient who had received radiotherapy before surgery. At the present stage of the study, therefore, we have no unequivocal evidence for the existence of MT-deficient Gliomas. | {
"pile_set_name": "PubMed Abstracts"
} |
Lattice mismatch as the descriptor of segregation, stability and reactivity of supported thin catalyst films.
The increasing demand and high prices of advanced catalysts motivate a constant search for novel active materials with reduced contents of noble metals. The development of thin films and core-shell catalysts seems to be a promising strategy along this path. Using density functional theory we have analyzed a number of surface properties of supported bimetallic thin films with the composition A3B (where A = Pt and Pd, and B = Cu, Ag and Au). We focus on the surface segregation, dissolution stability and surface electronic structure. We also address the chemisorption properties of Pd3Au thin films supported by different substrates, by probing the surface reactivity with CO. We find a strong influence of the support in the case of mono- and bilayers, while the surface strain seems to be the predominant factor in determining the surface properties of supported trilayers and thicker films. In particular, we show that the studied properties of the supported trilayers can be predicted from the lattice mismatch between the overlayer and the support. Namely, if the strain dependence of the corresponding quantities for pure strained surfaces is known, the properties of strained supported trilayers can be reliably estimated. The obtained results can be used in the design of novel catalysts and predictions of the surface properties of supported ultrathin catalyst layers. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of proteolytic cleavages of diabetes-associated protein IA-2 beta in the pancreas and the brain using novel anti-IA-2 beta monoclonal antibodies.
Insulinoma-associated protein (IA)-2 beta, an inactive member of the protein-tyrosine phosphatase (PTP) family, is a major autoantigen in type-1 diabetes mellitus. IA-2 beta exists mainly in a 60-kDa form, and is frequently located in the dense-core secretory vesicles of pancreatic beta cells. As IA-2 beta gene-deficient mice exhibit impaired insulin secretions, IA-2 beta is probably involved in insulin secretions. In the present study, we characterized the major forms of IA-2 beta in the brain and pancreas of normal and non-obese diabetic (NOD) mice. Novel monoclonal antibodies (mAbs) against IA-2 beta revealed that this brain protein was of multiple compositions incorporating the 60-, 64-, 67- and 71-kDa forms, which were designated as IA-2 beta 60, IA-2 beta 64, IA-2 beta 67 and IA-2 beta 71, respectively. On the contrary, only the 60-kDa isoform of IA-2 beta was expressed in the mouse pancreas and in the mouse pancreatic beta cell line, MIN6. Sequence analyses revealed that IA-2 beta 60, IA-2 beta 64 and IA-2 beta 71 (brain-derived immunoprecipitated IA-2 beta isoforms) contained alternative NH2- termini starting from Glu489, Ala464, and Ser414, respectively, while IA-2 beta 60 (an MIN6-derived immunoprecipitated IA-2 beta isoform) contained those from Glu489. Consistent with the lack of an NH2-terminal region of IA-2 beta, the isoforms were recognized by their respective mAbs characterized with different epitope regions. Furthermore, Western blotting and immunohistochemistry demonstrated that NOD mice expressed similar isoforms present in the brains and pancreatic islets of C57BL/6J, BALC/CA and ICR mice, accordingly. Taken together, these results suggest that IA-2 beta undergoes at least three distinct proteolytic cleavages. | {
"pile_set_name": "PubMed Abstracts"
} |
Chlorpromazine-induced histamine release from guinea-pig skin in vitro--a photosensitive reaction.
Chlorpromazine releases histamine from chopped guinea-pig skin maintained in vitro at 37 degrees C. This effect was markedly potentiated by radiant energy. This potentiation increased with increasing exposure to radiant energy. The possible clinical applications of these findings are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of early wound healing and wound treatment with zinc tape on intestinal absorption and distribution of zinc in rats.
In rats operated with large excisional skin wounds which were not treated with zinc tape, the serum zinc concentration was decreased at every observation time during the first post-operative day and the absorption of zinc from the intestine was increased. Slight decreases in the zinc concentration were seen in some tissues while liver zinc was very high. In rats with wounds treated with zinc tape, serum zinc was markedly increased at 6 hours, lower but above control levels at 7 and 12 hours and markedly increased again at 24 hours. The absorption of zinc from the intestine was low. Zinc concentration were elevated in most tissues sampled; they were high in testis and kidney and very high in liver. The results strongly indicate that the operative trauma and/or acute inflammatory conditions in the wounds in animals not treated with zinc tape initiate a movement of zinc from serum, some tissues and the content of the intestine to the liver. In the zinc tape treated group the increase in liver zinc was supplied mostly by the zinc tape. It is assumed that these large increases in zinc concentration in the liver are the result of the incorporation of zinc into certain zinc containing proteins which are produced in response to the inflammatory process in the wound. An increase was also found in the copper concentration in the liver of zinc tape treated animals and a decrease in the iron concentration in the liver of both groups of operated animals compared to controls. | {
"pile_set_name": "PubMed Abstracts"
} |
Knowledge gained from studies of leucine consumption in animals and humans.
Leucine's wide-ranging metabolic influences have made it subject to special interest. It is abundant in the diet, especially in some milk and cereal proteins, in part due to its allocation of 6 codons in the genetic code, and individual dietary intakes range up to >250 mg · kg(-1) · d(-1). It influences many cell functions by various mechanisms, which include allosteric activation of enzymes, enabling ATP generation and insulin secretion from the pancreatic islet cell, and activation of signaling pathways. It is a mediator of the anabolic drive of dietary amino acids, stimulating anabolic hormone secretion and directly signaling protein deposition and growth through the stimulation of protein synthesis and restraint of proteolysis. Its signaling may involve the mammalian target of rapamycin complex and rapamycin-insensitive pathways responding to a leucine "transceptor," which combines leucine cellular transport, fueled by the intracellular-extracellular glutamine gradient, and a signaling response to changes in ionic and water balance and cell volume. In animal studies, dietary leucine supplementation has reversed many of the adverse influences of a high-fat diet, consistent with a benefit for healthy weight maintenance in humans for which evidence is accumulating. The implications for safety of leucine-supplemented diets are discussed in terms of adversely lowering valine and isoleucine concentrations and inducing hyperammonemia through overloading peripheral glutamine synthetic pathways. Finally, the apparently high human leucine requirement is explained in terms of both an adaptive metabolic demand model of requirements and the design and analysis of human studies, which may overestimate values. | {
"pile_set_name": "PubMed Abstracts"
} |
Do intraindividual variation in disease progression and the ensuing tight window of opportunity affect estimation of screening benefits?
The effects of variation in disease progression between individuals on the effectiveness of screening have been assessed extensively in the literature. For several diseases, progression may also vary within individuals over time. The authors study the effects of intraindividual variation and the combined effects of inter- and intraindividual variation in disease progression on the effectiveness of screening. The authors investigated the risk reduction of aneurysmal subarachnoid hemorrhage (SAH) achieved by screening for intracranial aneurysms in a simulation study as a function of the inter- and intraindividual variation in the risk of aneurysm rupture. They also extended a previously constructed Markov model for the cost-effectiveness analysis of screening for new aneurysms in patients with clipped aneurysms after SAH. A time-varying risk of aneurysm rupture was introduced, and the influence of this variation on cost-effectiveness was assessed. The risk reduction provided by screening decreased with increasing intraindividual variation in disease progression. The expected number of prevented instances of SAH was overestimated by 58% in this simulation study when high degrees of inter- and intraindividual variation were present. Interindividual variation alone resulted in up to 33% overestimation and intraindividual variation in up to 43% overestimation. In the extended Markov model, screening benefits were overestimated by 24% when a high degree of intraindividual variation was present but ignored. If intraindividual variation in disease progression is ignored in decision models, subsequent cost-effectiveness analyses of screening strategies will overestimate the benefits provided by screening. This bias is comparable to, but partially independent of, the bias caused by ignoring interindividual heterogeneity. | {
"pile_set_name": "PubMed Abstracts"
} |
E4021, a selective phosphodiesterase 5 inhibitor, potentiates the vasodilator effect of inhaled nitric oxide in isolated perfused rat lungs.
To test whether E4021, a potent selective cyclic guanosine 3'-5'-monophosphate (cGMP) phosphodiesterase inhibitor, causes pulmonary vasodilation and whether it enhances the vasodilator action of inhaled nitric oxide (NO), we studied its effects on pulmonary vascular tone and inhaled NO-induced pulmonary vasodilation in isolated perfused rat lungs. Lungs were perfused at a constant flow rate with salt-Ficoll solution and ventilated with air plus 5% CO2. After equilibration, vasodilator responses to either E4021, inhaled NO, or both were evaluated under conditions of increased perfusion pressure induced by infusion of U46619. E4021 had no effect on the baseline perfusion pressure, whereas it caused dose-dependent pulmonary vasodilation when the vasomotor tone was increased by U46619. Inhaled 1, 5, and 20 ppm NO reduced the increased perfusion pressure by 60+/-5%, 83+/-3%, and 92+/-2%, respectively. Pretreatment with E4021 significantly potentiated the vasodilator effect of 1 ppm NO (from 53+/-6% to 71+/-2%; p < 0.05) but did not alter that of 5 ppm NO (from 77+/-3% to 78+/-4%; p > 0.05). In addition, pretreatment with E4021 significantly augmented the vasodilator response to sodium nitroprusside but not to isoproterenol. These results indicate that E4021 causes pulmonary vasodilation and potentiates the vasodilator effect of low concentrations of inhaled NO, probably through a cGMP-dependent mechanism in salt-solution perfused rat lungs. We conclude that E4021 may possibly be useful for the treatment of pulmonary hypertension, either alone or in combination with inhaled NO. | {
"pile_set_name": "PubMed Abstracts"
} |
Organically vs conventionally grown winter wheat: effects on grain yield, technological quality, and on phenolic composition and antioxidant properties of bran and refined flour.
Since organic food is widely assumed to have a better nutritional quality than conventional food, our aim was to study the effects of organic vs conventional cropping systems on yield and the phenolic composition of winter wheat cv. 'Bologna'. Although organic wheat yielded less than conventional wheat, mainly due to the nitrogen shortage, and its bread-making quality was lower, the cultivation system did not affect the total amounts of phenolics and phenolic acids. Of the eight phenolic acids identified, only ferulic acid was influenced by the cultivation system. Phenolic composition and quantity were significantly affected by the milling fraction (bran or white flour): phenolics were more concentrated in the bran, which showed the highest antioxidant power. Under the conditions adopted in this study, an organic cropping system can maintain or even increase the health properties of the wheat milled products, provided a reduction in grain yield is accepted. | {
"pile_set_name": "PubMed Abstracts"
} |
From false belief to friendship: commentary on Fink, Begeer, Peterson, Slaughter, and de Rosnay.
Fink, Begeer, Peterson, Slaughter, and de Rosnay (Brit. J. Dev. Psychol, 2015; 33, 1-17) represent a welcome contribution in providing empirical evidence of the link from false belief understanding at Time 1 to mutual friendship 2 years later, controlling for several other possible contributors. This opens a new and important line of inquiry into the practical significance of a Theory of Mind. As is typical of pioneering research, further study is needed to address some issues; here, we point out some of these issues and then briefly discuss the broader implications of Fink et al.'s findings. | {
"pile_set_name": "PubMed Abstracts"
} |
Absence of an association between enteric parasites in the manifestations and pathogenesis of HIV enteropathy in gay men. The GI/HIV Study Group.
49 gay men confirmed to be infected with the human immunodeficiency virus (HIV) and 9 HIV seronegative gay men participated in a pilot study comparing clinical status and enteric parasite load with gastrointestinal structure, function and symptomatology. Cases included 16/49 (33%) men who were CDC stage II, 7/49 (14%) who were CDC stage III, and 26/49 (53%) who were CDC stage IV. The mean CD4-lymphocyte count was 476 +/- 199 (SD)/microliter. The prevalence of enteric parasitic flora was similar in HIV seropositive patients and controls. Seven cases had enteric infection with pathogenic agents including 3 patients with Entamoeba histolytica, and 4 patients with Giardia lamblia, one of whom also had cryptosporidiosis. Other cases were most frequently colonized with Blastocystis hominis (44%) and Endolimax nana (41%) regardless of the HIV clinical status. HIV seropositive patients with enteric parasitic colonization tended to have lower mean levels of serum IgA than cases without parasites. Duodenal morphometric mucosal changes demonstrated a significant decrease in the mean villous height (p < 0.01) with no elongation of the crypt depth in HIV-infected patients with and without diarrhea compared to controls. Despite gastrointestinal symptoms including diarrhea and weight loss being more prevalent in HIV infected individuals than controls, no correlations were found between the presence of particular enteric parasites, gastrointestinal symptomatology, the clinical HIV status of the CD4-lymphocyte count, the malabsorption of D-xylose or morphometric changes in the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Homograft replacement of the tympanic membrane.
This paper presents the authors' experiences with one method of reconstruction of the tympanic membrane when it is totally absent or when there is a fixed, retracted, defective, or absent malleus. Ten patients undergoing surgery for chronic suppurative otitis media between April, 1971, and January, 1973, had homograft tympanic membranes and/or ossicles used to reconstruct the defect in the tympanic membrane or ossicular mechanism. The patients had certain clinical and surgical characteristics in common: 1. all had either an absent tympanic membrane or almost total perforation of it; 2. all were operated upon in the absence of acute infection or active drainage; cholesteatoma, if present, was totally removed; 3. all had patent eustachian tubes; 4. all had intact middle ear mucosa at the time of utilization of the homograft; 5. all patients were operated upon by the same surgeon; 6. all of the homografts were obtained within 24 hours and were used within one month after the death of the donor; 7. all of the homografts used had been preserved in 70 percent ethyl alcohol; 8. all of the homograft materials came from donors who were under 40 years of age at the time of death and who died of accidental causes. (None of the donors was known to have any pre-existing disease); 9. all homografts, after being placed in proper position in the recipient, were covered with ear canal skin; 10. all patients received homografts that were from the corresponding ear of the donor. (In other words, right ear homografts were used in the patient's right ear, etc.); 11. whenever the tympanic ring was greater than the size of the homograft, the patient's temporalis fascia was used in conjunction with the homograft tympanic membrane to bridge the defect; 12. all patients had the middle ear packed with gelfoam prior to inserting the homograft (compressed gelfoam was used also for the outer packing); 13. none of the patients had tissue-typing procedures carried out in an effort to match the donor and the recipient, nor was any attempt made to match the sex of the donor and the recipient; and 14. all patients received antibiotics postoperatively; however, none received immunosuppressive therapy postoperatively. In 3 of 10 patients receiving homografts, the malleus was normal, and only the tympanic membrane was reconstructed. In seven others there was a fixed, retracted, defective or absent malleus in addition to the tympanic membrane defect.(ABSTRACT TRUNCATED AT 400 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
The impact of BRCA1 on spina bifida meningomyelocele lesions.
We examined the BRCA1 gene in 268 patients, and their parents, with a specific diagnosis of spina bifida meningomyelocele (SBMM). We genotyped two intragenic microsatellite markers (BRCA1 D17S1323, BRCA1 D17S1322) and 2 single nucleotide polymorphisms (A1186G, A4956G) in our patients. Transmission disequilibrium testing (TDT) showed significant association with A4956G, but not with A1186G. Extended TDT demonstrated over-transmission of the 17GT allele in BRCA1 D17S1323 and the 14GTT allele in BRCA1 D17S1322, and under-transmission of the 20GT allele in BRCA1 D17S1323 and the 16GTT allele in BRCA1 D17S1322. Our data included location of the rostral edge of the lesion. Individuals homozygous for the 17GT allele for BRCA1 D17S1323 were more likely to have SB lesions located caudally, while heterozygotes with the 17GT allele for BRCA1 D17S1323 had a more rostral lesion. Individuals heterozygous for the 16GTT allele of BRCA1 D17S1322 were more likely to have rostral lesions. We measured gene expression in CEPH members and demonstrated differential expression levels of BRCA1 associated with these polymorphisms. Integrating our data with HapMap findings showed that the polymorphic markers are associated with distinct haplotypes. We conclude that the BRCA1 gene is associated with SBMM and participates in the phenotypic variability seen in SBMM. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation and identification of cholesteryl alkyl ethers from bovine cardiac muscle.
Cholesteryl alkyl ethers have been isolated from bovine cardiac muscle and characterized by thin-layer and gas-liquid chromatography. The fraction contained at least three homologues. Cholesteryl hexadecyl ether, which accounted for over 90% of the total components observed on gas chromatography, was identified by mass spectrometry. | {
"pile_set_name": "PubMed Abstracts"
} |
Spatial-frequency tuning in the pooling of one- and two-dimensional motion signals.
Cortical neurons that initially extract motion signals have small receptive-fields, and narrow orientation- and bandpass-spatial-frequency tuning. Accurate extraction of the veridical motion of objects typically requires the global pooling of the output of multiple local-motion units across orientation and space. We examined whether the narrow spatial-frequency tuning present at the local-motion level is preserved at the global-motion-pooling stage. Stimuli consisted of numerous drifting Gabor or plaid elements that were either signal (carrier drift-speed consistent with a given global-motion vector) or noise (drift speed consistent with a random, noise vector). The carrier spatial-frequencies of the signal and noise elements were independently varied. Regardless of the frequency of the signal elements, broad low-pass masking functions were obtained for both Gabor (one-dimensional) and Plaid (two-dimensional) conditions when measuring the threshold signal ratio for identification of the global-motion direction. For the Gabor stimuli, this pattern of results was also independent of the relative orientations of the signal and noise elements. These results indicate that in the global-motion pooling of one-dimensional and two-dimensional signals, local-motion signals of all spatial frequencies are pooled into a single system that exhibits broadband, low-pass tuning. | {
"pile_set_name": "PubMed Abstracts"
} |
[Crystal-induced activation of the inflammasome: gout and pseudogout].
Crystals in tissues lead the innate immune system to the same kind of acute response seen with pathogens. Via activation of the inflammasome, interleukin-1 (IL-1) is released, which upregulates mediators such as cyclooxygenase, tumor necrosis factor, and IL-8 and induces an acute granulocytic inflammation. Therefore, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and colchicine, IL-1 blockers appear to be effective. Large clinical trials have already been initiated. Such an approach could constitute a valuable alternative for patients with contraindications or insufficient response to NSAIDs. After the attack has subsided, control of uric acid metabolism is central. At least several of the responsible urate transporters have been unraveled, which could lead to more focused therapy in the future. At present, diet and blockade of uric acid synthesis remain the main pillars of therapy. The new xanthine oxidase inhibitor febuxostat constitutes a novel option for patients with renal insufficiency or intolerance to allopurinol. | {
"pile_set_name": "PubMed Abstracts"
} |
[Mechanical infertility in the female population of the Kielce province. IV. Evaluation of hypophyseal gonadotropin levels during the [Mechanical infertility in the female population of the Kielce province. IV. Evaluation of hypophyseal gonadotropin levels during the menstrual cycle].
The paper describes results of the RIA of the hypophyseal gonadotropins estimated in the menstrual cycle in the group of women with mechanical sterility in confrontation with the group of fertile women. Significantly higher mean concentration of FSH in follicular and luteal phase and higher concentration of LH after ovulation in the group of sterile women were found. There was no LH peak and mean concentration in 14th day of menstrual cycle was significantly lower in the group of women with mechanical sterility. Mean PRL concentration was higher but within the bounds of standard in sterile women. | {
"pile_set_name": "PubMed Abstracts"
} |
Sleep-EEG in dizygotic twins discordant for Williams syndrome.
Reports on twin pairs concordant and discordant for Williams syndrome were published before, but no study unravelled sleep physiology in these cases yet. We aim to fill this gap by analyzing sleep records of a twin pair discordant for Williams syndrome extending our focus on presleep wakefulness and sleep spindling. We performed multiplex ligation-dependent probe amplification of the 7q11.23 region of a 17 years old dizygotic opposite-sex twin pair discordant for Williams syndrome. Polysomnography of laboratory sleep at this age was analyzed and followed-up after 1.5 years by ambulatory polysomnography. Sleep stages scoring, EEG power spectra and sleep spindle analyses were carried out. The twin brother showed reduced levels of amplification for all of the probes in the 7q11.23 region indicating a typical deletion spanning at least 1.038 Mb between FKBP6 and CLIP2. The results of the twin sister showed normal copy numbers in the investigated region. Lower sleep times and efficiencies, as well as higher slow wave sleep percents of the twin brother were evident during both recordings. Roughly equal NREM, Stage 2 and REM sleep percents were found. EEG analyses revealed state and derivation-independent decreases in alpha power, lack of an alpha spectral peak in presleep wakefulness, as well as higher NREM sleep sigma peak frequency in the twin brother. Faster sleep spindles with lower amplitude and shorter duration characterized the records of the twin brother. Spectra show a striking reliability and correspondence between the two situations (laboratory vs. home records). Alterations in sleep and specific neural oscillations including the alpha/sigma waves are inherent aspects of Williams syndrome. | {
"pile_set_name": "PubMed Abstracts"
} |
A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients.
ISIS 14803 is a 20-unit antisense phosphorothioate oligodeoxynucleotide that binds to hepatitis C virus (HCV) RNA at the translation initiation region of the internal ribosome entry site (IRES) and inhibits protein expression in cell culture and mouse models. This Phase I, open-label, dose-escalation trial of ISIS 14803 was performed in chronic HCV patients. At least 7 days after receiving an initial single dose, twenty-eight patients received 0.5-3 mg/kg ISIS 14803 thrice weekly for 4 weeks by intravenous infusion or subcutaneous injection. In most patients, the 4-week treatment did not reduce plasma HCV RNA. However, 3 patients receiving > or =2 mg/kg had transient HCV reductions of 1.2-1.7 log(10) that persisted < or =32 days. These reductions were accompanied by asymptomatic, self-resolving elevations in serum alanine transaminase (ALT) levels to >10x the upper limit of normal. Two other patients had ALT flares without plasma HCV reduction. No clinical signs, symptoms of hepatic dysfunction, or laboratory changes in albumin or prothrombin time accompanied ALT elevations. ISIS 14803 treatment was associated with HCV reductions in only 3/28 patients. ALT flares in 5 patients also occurred. Further studies to evaluate ISIS 14803 treatment and the mechanisms of the ALT flares are now required. | {
"pile_set_name": "PubMed Abstracts"
} |
A balanced approach to the detection, characterisation and mechanism of the toxicity of industrial chemicals.
Several thousands of new chemical entities are synthesised each year in the laboratories of the world. Currently there are estimated to be some 100,000 substances used commercially of the 7 million chemicals recorded by chemical abstracts (Ca 1.5%). Public attention is mainly attracted to the potential life threatening and ill health effects of chemicals such as systemic poisoning, carcinogenicity, teratogenicity and mutagenicity, although there are relatively few proven human chemical carcinogens, teratogens or mutagens. Many substances have been examined in animal toxicity studies for their acute toxic effects, far fewer for chronic toxic effects. The public's perception is that chemicals are toxic. In our laboratory, minimal to no lethal toxic effects were recorded for more than 60% of substances examined at doses below 2000 mg/kg/bwt by either oral or dermal routes. A similar spectrum of chemicals did not elicit skin or ocular irritant or skin sensitisation response in 70-80% of studies. Perversely although toxicity studies reasonably predict the probable human response following exposure, they are a focus of a strong public lobby supported by many scientists to curtail studies in experimental animals. Consequently, much effort is devoted towards the development of "alternative" in vitro and ex-vivo procedures. Often these are empirically based without consideration of the underlying fundamental physiology, biochemistry or toxic mechanism of action. Consequently there can be an over-estimation or expectation of their ability to predict potential toxicity. Attention is seldom directed towards the design requirements of the validation studies needed to test, performance and reproducibility and the evaluation of the parameters of sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Photoinduced Rydberg ionization spectroscopy of phenylacetylene: vibrational assignments of the C state of the cation.
The photoinduced Rydberg ionization spectrum of the third excited electronic state of phenylacetylene cation was recorded via the origin of the cation ground electronic state. The origin of this state is 17 834 cm(-1) above the ground state of the cation, and the spectrum shows well-resolved vibrational features to the energy of 2200 cm(-1) above this. An assignment of the vibrational structure was made by comparison to calculated frequencies and Franck-Condon factors. From the assignments, and electronic structure considerations, the electronic symmetry of the C state is established to be (2)B(1). | {
"pile_set_name": "PubMed Abstracts"
} |
[Efficiency of use of resources in intensive care units in an urban area].
2710 patients were admitted during 1988 in 14 ICU of a crowded urban area. We determined OMEGA score at the end of the ICU stay. OMEGA scores the intensity of the treatment and depicts the utilisation of resources giving rise to the variable costs. 2085 patients intensively treated resulted in a higher mean OMEGA score than 625 patients only monitored, the length of ICU stay over 8th day increases the allocation of resources. This was conditioned also by the diagnosis in both groups of patients being liver transplant (OLTX) and chronic obstructive lung diseases (COLD), the most resources-consuming intensive patients and cardiovascular (CARD), and drug intoxication (TS), the least ones. The efficiency of the use of resources (i.e. use in survivors) in ICU treatment was 100% in monitored patients and ranges from 47.3% to 90.9% in intensively treated ones: medical unspecified (Mm), COLD, strokes, surgical unscheduled, cardiac arrest, OLTX, pneumonia and ARDS, pulmonary embolism, surgical scheduled, trauma, neurological diseases, TS. Intensive patients could be divided in a group with a good utilization (26.5%) of employed resources: TS, PE, CARD, SS, TR, PNM, NRL, OLTX) in a group with a mean utilisation (50-65%: CCA, strokes, SU) and finally in a group with a weak utilisation of resources (Mm and COLD). We computed also the mean loss of resources for each diagnosis that ranges from COLD (76.1 OMEGA points) to OLTX, strokes, Mm, SU, PNM, CCA, NRL, TR, CARD, SS, PE, and TS (10.2 points). The implications of these results and the possibilities of improving the utilisation of resources in ICU are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Neuronal survival: early dependence on Schwann cells.
Schwann cells fail to develop in mouse embryos lacking functional ErbB3 neuregulin receptors, and most sensory and motor neurons subsequently die in these mice. As ErbB3 acts cell autonomously in Schwann cell development but not in neuronal survival, neurons may depend on Schwann cells for survival. | {
"pile_set_name": "PubMed Abstracts"
} |
Total Gastrectomy with Roux-En-Y esophagojejunostomy for Chronic Complicated Post-Sleeve Gastric Fistula-Video Report.
Laparoscopic sleeve gastrectomy (LSG) has become one of the most popular bariatric surgeries worldwide. However, complications related to the stapler line can be very serious. Among several challenging post-LSG complications, fistula is the most feared. Its management can be very challenging and chronic. In case of chronic fistula and failure of surgical, endoscopic, and radiological treatment, total gastrectomy with esojejunal anastomosis (RYOJ) can be considered as an effective solution. We describe in this video the steps of our laparoscopic technique. We have performed a total gastrectomy with RYOJ in a particular patient with chronic and persisting gastric fistula 9 months after LSG. The body mass index (BMI) was initially 50 kg/m2 at the time of the LSG against 31 kg/m2 on the day of the RYOJ. The postoperative course was uneventful. An upper GI series was done at 1 week and 1 month postoperatively without any abnormality. The patient was evaluated clinically and biologically at 1, 3, and 6 months later on with no evidence of dysphasia or biological abnormality. RYOJ in our particular case was efficient. However, longer series and longer follow-up are needed to confirm the effectiveness of this rescue procedure. | {
"pile_set_name": "PubMed Abstracts"
} |
Sodium Excretion and Cardiovascular Structure and Function in the Nonhypertensive Population: The Korean Genome and Epidemiology Study.
The effect of sodium intake on the cardiovascular system remains controversial. The purpose of this study is to investigate the relation between sodium intake and cardiovascular structure and function in the nonhypertensive population. We performed a cross-sectional analysis in 1,586 nonhypertensive subjects who participated in the Korean Genome Epidemiology Study (2007-2008). Sodium intake was assessed by estimating the 24-hour urinary sodium excretion from a spot urine sample. Changes in cardiovascular structure and function were assessed by using tissue Doppler echocardiography, the carotid intima-media thickness (CIMT), and the brachial-ankle pulse wave velocity (baPWV). Systolic and diastolic blood pressures increased with increasing tertiles of estimated 24-hour urinary sodium excretion. In multivariate analyses adjusting for covariates, there were stepwise decreases in the baPWV (P = 0.003) and CIMT (P = 0.001) values as the estimated 24-hour urinary sodium excretion increased, whereas no significant differences in left ventricular (LV) structural and functional parameters were observed across the tertiles of estimated 24-hour urinary sodium excretion. Multiple linear regression analyses revealed that the estimated 24-hour urinary sodium excretion was independently and inversely associated with baPWV (P < 0.001) and CIMT (P = 0.001), but not with LV parameters. In the nonhypertensive population, urinary sodium excretion was inversely related to baPWV and CIMT. However, there were no associations between urinary sodium excretion and LV structure or function. | {
"pile_set_name": "PubMed Abstracts"
} |
Line probe assay for detection of rifampicin and isoniazid resistant tuberculosis in Pakistan.
To assess the efficacy of a line-probe assay delta (LiPA) as rapid diagnostic test for early detection of drug-resistant tuberculosis compared to conventional susceptibility methods in Pakistan. Resistance to rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis samples was detected using a line-probe assay [GenoType MTBDRplus (Hain Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of Aga Khan University Hospital in May, 2009. Results were compared with susceptibilities performed while using agar proportion. In comparison to the agar proportion method, the detection rate and specificity of resistance using MTBDR plus was 92.5% and 98.2% for rifampicin, and 76.3% and 100% for isoniazid. Mutations in codons 531 and 533 of rpoB gene (62%S531L) were responsible for 67.9% of rifampicin resistance. S315T mutation of katG gene was detected in 55.9% and inhA promoter mutation at positions -15 (C15T) in 11.9% of isoniazid resistant isolates. Four phenotypically rifampicin-resistant and 14 isoniazid-resistant strains were not detected by MTBDRplus. Sequencing these strains revealed mutations in 4 strains; 2 in rpoB gene S531W, del518 and 2 in katG genesW300L, S315N. Hence, two phenotypic rifampicin-resistant and 13 phenotypic isoniazid-resistant strains were not detected by the commercial line probe assay. The study showed that MTBDRplus had a high detection rate for rifampicin resistance. However, additional probes need to be included in the assay to improve the detection of isoniazid-resistant mycobacterium tuberculosis strains in Pakistan. | {
"pile_set_name": "PubMed Abstracts"
} |
Outside-to-inside signaling through transmembrane tumor necrosis factor reverses pathologic interleukin-1beta production and deficient apoptosis of rheumatoid arthritis monocytes.
Monocytes are a major source of proinflammatory cytokines in rheumatoid arthritis (RA), and inhibitors of monocytic cytokines are highly efficient agents for treatment of the disease. The aim of this study was to analyze the effects of a therapeutic anti-tumor necrosis factor alpha (anti-TNFalpha) antibody on monocytes from patients with RA and healthy control subjects. Peripheral blood monocytes from patients with RA and healthy control subjects were incubated in the presence of anti-TNFalpha antibody or IgG. Annexin V staining, caspase activation, poly(ADP-ribose) polymerase cleavage, and DNA staining with propidium iodide were used to analyze apoptosis. The signaling events elicited in monocytes by infliximab were analyzed by Western blotting and electromobility shift assay. Peripheral blood monocytes from patients with RA were characterized by increased expression of transmembrane TNFalpha, spontaneous in vitro production of interleukin-1beta (IL-1beta), and a decreased rate of spontaneous ex vivo apoptosis. Incubation with infliximab induced significantly increased apoptosis in monocytes from patients with RA but not in monocytes from healthy control subjects. This apoptosis was triggered by reverse signaling of transmembrane TNF after ligation by infliximab and was independent of caspase activation. Instead, transmembrane TNF reverse signaling inhibited the constitutive NF-kappaB activation in RA monocytes, suppressed IL-1beta secretion, and normalized spontaneous in vitro apoptosis. This normalization was reversible by the addition of exogenous IL-1beta. This study demonstrates that outside-to-inside signaling through transmembrane TNF after ligation by infliximab inhibits constitutive NF-kappaB activation and suppresses spontaneous IL-1beta production by monocytes from patients with RA. Besides the induction of monocyte apoptosis, this inhibition could also contribute to the therapeutic effects observed during treatment with TNFalpha inhibitors. | {
"pile_set_name": "PubMed Abstracts"
} |
Protein kinase C phosphorylates P-glycoprotein in multidrug resistant human KB carcinoma cells.
Studies were undertaken to identify the protein kinase(s) responsible for P-glycoprotein phosphorylation in multidrug-resistant (KB-V1) human carcinoma cells and to elucidate the functional role of phosphorylation. P-glycoprotein migrated on sodium dodecyl sulfate gels with apparent Mr 150,000 and is termed P150. When KB-V1 membrane vesicles were incubated with [gamma-32P] ATP, P150 was phosphorylated by an endogenous kinase that exhibited properties of membrane-inserted protein kinase C (PKC). Both membrane-bound P150 and purified P150 served as effective substrates for highly purified rat brain PKC which incorporated approximately 0.6 mol of phosphate/mol of P150. Enzyme assays showed that KB-V1 cells exhibit 4-fold higher PKC activity compared with the drug-sensitive KB-3 cell line. The basal phosphorylation of P150 observed in 32P-labeled cells was increased 2-fold by phorbol ester (PMA) treatment and reduced 30% by treatment with the isoquinolinsulfonamide H-7. Phosphopeptide maps of partially digested P150, phosphorylated either in vitro with PKC or in intact 32P-labeled control or PMA-stimulated cells, were indistinguishable from one another. Drug accumulation assays revealed that PMA treatment of KB-V1 cells significantly reduced [3H]vinblastine accumulation induced by verapamil or by tetrandrine. The results suggest that PKC is primarily responsible for P150 phosphorylation in KB-V1 cells and that phosphorylation may play a modulatory role in the drug transport process. | {
"pile_set_name": "PubMed Abstracts"
} |
Cloning and sequence analysis of tumor-associated gene hMMTAG2 from human multiple myeloma cell line ARH-77.
In order to look for the tumor-associated genes from human multiple myeloma (MM), a cDNA library of human multiple myeloma cell line ARH-77 was constructed with eukaryote expression vector pcDNA3.1(+). The length of inserted fragments in library was 1.2 kb in average. All clones in cDNA library were transferred in situ to nylon membrane, which was divided into eight equal parts (A-H) and cultured in LB medium to set up gene pools. The plasmids in cDNA library and in gene pools were extracted and NIH/3T3 cells were transfected respectively. By G418 screening and colonies counting, gene pool A was chosen for the second cycle transfection. After several cycles, a clone, A62-17, was obtained, which had significant transforming ability. The length of this clone was 993 bp. The RACE technique was used for rapid amplification of A62-17 5'-end. The full length of this sequence has 1300 bp and was named as hMMTAG2 gene. hMMTAG2 consists of 8 exons and codes for a polypeptide of 263 amino acids (the accession number in GenBank: AY137773). It was located at chromosome 1q42.13. hMMTAG2 had same transforming activities in NIH/3T3 cells as the clone A62-17, and the number of transformant foci was 6 folds more than the blank vector pcDNA3.1(+). The analysis of bioinformatics revealed that hMMTAG2 had many phosphorylation sites for several protein kinases, N-myristoylation sites and nuclear localization signals, so it may be a signal molecule in the nucleus. | {
"pile_set_name": "PubMed Abstracts"
} |
Heavy metals and the mammalian thymus: in vivo and in vitro investigations.
This experiment was performed to investigate changes in the thymus of Wistar-strain male rats administered cadmium chloride (CdCl2), mercuric chloride (HgCl2), and lead chloride (PbCl2) salts. The study involved measurement of: 1) deoxyribonucleic acid (DNA) content; 2) ascorbic acid (vitamin C) content; 3) incorporation of 3h-thymidine during in-vitro investigation; and 4) histological and morphological changes. It was shown in investigations on DNA content that administration of heavy metal salts caused an average 76% decrease in DNA content compared to the control. Moreover, in the thymus of experimental animals, an average 69% decrease in vitamin C content was recorded. In in vitro cultures, heavy metal salts decreased the incorporation of 3H-thymidine in thymic cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Intravesical therapy with adriamycin in urothelial dysplasia and early carcinoma in situ.
The authors studied the effect of instilling Adriamycin intravesically in 21 patients with urothelial dysplasia and early carcinoma in situ. The effectiveness of the treatment was assessed by repeated urine cytology, cystoscopy and repeated biopsy of the bladder mucosa. No serious side effects were noted. Adriamycin causes the death of malignant cells, general improvement in the appearance of the bladder mucosa at cystoscopy and histologic evidence of endothelial damage to the bladder mucosa. The cytologic changes continue for many months after treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
An immunolocalization study of tissue inhibitors of metalloproteinase-1 of bone graft healing on parietal bone.
This immunolocalization study was performed to investigate the temporal and spatial expression of tissue inhibitors of metalloproteinase (TIMP) 1 within endochondral and intramembranous bone grafts during the early stages of healing, in the hope of gaining a better understanding of the mechanisms of bone graft healing, which could influence the choice of bone graft used. Twenty-seven adult New Zealand White rabbits were used as the experimental model. Autogenous bone grafts taken from the cranial bone (intramembranous in origin) and the femur (endochondral in origin) were grafted into skull defects created on either side of the parietal suture. Rabbits were killed on days 1 to 9 postgrafting, and the bone graft alone was harvested for immunolocalization of TIMP-1. In endochondral bone grafts, TIMP-1 was expressed on days 1 to 3, followed by a period of absence until days 8 and 9. Intramembranous bone grafts did not express TIMP-1 until days 6 to 9. The timing and location of TIMP-1 expression coincided with osteogenesis, which indicates a role for TIMP-1 in preserving newly formed bone during the initial stages of graft healing. The differential temporal expression of TIMP-1 in endochondral and intramembranous bone grafts suggests that bone graft type plays an important role in influencing the healing process mediated by the host tissues. The earlier expression of TIMP-1 in endochondral bone grafts could be the reason for delayed vascularization of defects containing these grafts, whereas the delayed expression of TIMP-1 in intramembranous bone grafts could allow earlier vascularization of the intramembranous bone grafts. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of novel bepotastine salicylate salt bioequivalent to the commercial bepotastine besilate in beagle dogs.
To develop a novel salt form of bepotastine with bioequivalent to the commericial bepostastine besilate, bepostastine salicylate was prepared and its physicochemical properties were investigated. Furthermore, the bepotastine salicylate-loaded tablet was prepared by the wet granulation method, and the dissolution and bioavailability in beagle dogs were evaluated compared to the bepotastine besilate-loaded commercial product. Bepotastine salicylate improved the solubility of bepotastine, and the extent of solubility improvement by salicylate form was similar to that by besilate form. However, this novel salt exhibited negligible hygroscopicity similar to besilate form, and showed slightly higher melting point than besilate form. It was stable in various pH solutions. Furthermore, the bepotastine salicylate-loaded tablet composed of bepotastine salicylate, microcrystalline cellulose, D-mannitol, povidone, sodium starch glycolate and sodium stearyl fumarate at the weight ratio of 9.63/60.97/38/3.6/6/1.8 showed similar dissolution to the bepotastine besilate-loaded commercial product in water, pH 1.2, pH 4.0 and pH 6.8 and was bioequivalent to the commercial product in beagle dogs. Thus, this bepotastine salicylate-loaded tablet would be a promising candidate with bioequivalence to the bepotastine besilate-loaded commercial product. | {
"pile_set_name": "PubMed Abstracts"
} |
Etoposide-containing regimens with autologous bone marrow transplantation in children with malignant brain tumors.
Despite improvements in neurosurgical and neuroradiotherapeutic techniques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensification of effective chemotherapeutic agents followed by autologous bone marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administered to 11 children with malignant brain tumors: 10 had recurrent (n = 8) or progressive (n = 2) disease, and 1 was treated before progression. The histological diagnoses were medulloblastoma (3), glioblastoma multiforme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocytoma (1), and anaplastic oligodendroglioma (1). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative regimen included BCNU 600 mg/m2 and VP16 1500 mg/m2 in 5 cases, and thiotepa 900 mg/m2 and VP16 1500 mg/m2 in 6 cases. The median times to achieve a neutrophil count over 0.5 x 10(9)/l and a platelet count over 50 x 10(9)/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III-IV) was 18% and consisted of oropharyngeal mucositis and diarrhea. Among the 6 patients with measurable disease at the time of BMT there were 2 with stable disease, whereas 4 patients had tumor progression: all these patients died of tumor recurrence 2-10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a median follow-up of 20 months (range 3-67). These preliminary results show that high-dose chemotherapy and BMT may be effective in children with malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable. The most important variable prognostic for progression-free survival is the disease status at the time of transplantation. | {
"pile_set_name": "PubMed Abstracts"
} |
Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.
To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs. | {
"pile_set_name": "PubMed Abstracts"
} |
RAAS inhibition and renal protection.
Chronic kidney disease has become a major public health problem worldwide mainly as a consequence of the emerging epidemic of hypertension, diabetes, and obesity. It is currently estimated that nearly 15% of the general population has some degree of renal damage, a figure that reaches 50% in at-risk subgroups. Renin-angiotensin-aldosterone system (RAAS) inhibitors represent the agents of choice to control hypertension and reduce urinary albumin excretion, thereby delaying renal function deterioration. Greater blockade of the RAAS either by the combined use of multiple drugs or by supramaximal doses of single agents may provide greater renal protection. Furthermore, it has been proposed especially in the presence of proteinuria. However, at this time there is insufficient evidence to routinely recommend this therapeutic approach in patients with chronic kidney disease. The present article examines the currently available evidence and practical implications of pharmacological disruption of RAAS activity for renal protection. | {
"pile_set_name": "PubMed Abstracts"
} |
Larval development assay for detection of anthelmintic resistance in cyathostomins of Swedish horses.
The aim of this study was to investigate the suitability of a larval development assay (LDA) for the determination of anthelmintic resistance in cyathostomin nematode populations of the horse. In addition, comparison of results between geographic regions, types of horse establishment, and the use of anthelmintics in Sweden, was established. Seventy horse herds from different parts of Sweden were sampled, and strongyle eggs from the faeces of 54 of those were investigated by an LDA (DrenchRite). The following anthelmintics were tested: thiabendazole (TBZ), levamisole (LEV), ivermectin monosaccharide (IVM-MS), ivermectin aglycone (IVM-AG) and pyrantel (PYR). The LC50 values for TBZ and LEV were generally lower than those previously reported in other LDA studies on horse nematodes. This could be related to the infrequent use of these compounds for the past 20 years in Sweden. In this study, there was a great variation within and between assay plates that could not be explained. Still the LC50 values differed significantly between the regions for all anthelmintics, except for pyrantel. The highest LC50s were observed in parasite populations from the south of Sweden. There were no significant differences between riding schools and studs. Limitations of this technique exist, namely the lack of established cut-off values for susceptible and resistant populations and interpretation problems related to multi-species infections. Although there are advantages with LDA such as the possibility of testing several compounds simultaneously without interference with the deworming programmes on the farms, we conclude that LDA currently is not a reliable alternative to the faecal egg count reduction test (FECRT). | {
"pile_set_name": "PubMed Abstracts"
} |
The effect of tiotropium on the pulmonary diffusing capacity.
To our knowledge, there is no data on the effect of tiotropium on pulmonary gas exchange in healthy subjects. The aim of this study was to assess the effects of tiotropium on pulmonary diffusing capacity. Twenty-one healthy volunteers were enrolled for a prospective, randomized, double-blind, placebo-controlled study. Spirometric measurements, including pulmonary-diffusing capacity, were obtained before and after inhalation of drug or placebo. There was a significant decrease in forced vital capacity (FVC) and, consequently, an increase in the forced expiratory volume in one second (FEV1) to FVC ratio after placebo inhalation (p < 0.05), but no changes were found for percent-predicted FVC, FEV1, percent-predicted FEV1, percent-predicted forced expiratory flow (FEF25%-75%), percent-predicted peak expiratory flow (PEF), diffusing capacity of the lung for carbon monoxide (DLCO), single-breath alveolar volume (VA) and DLCO/VA ratio when compared with the baseline. Tiotropium inhalation caused a significant increase in FVC, percent-predicted FEV1, FEV1/FVC and percent-predicted FEF25%-75%, although the decrease in DLCO was insignificant (12.4 +/- 0.9 to 11.4 +/- 0.9). In conclusion, tiotropium does not change the pulmonary-diffusing capacity in healthy volunteers. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of quantitative thin layer chromatography using staining reagents.
Thin layer chromatography (TLC) using staining reagents is a superior method for analyzing organic compounds without chromophores. It is fast, versatile and sometimes the only viable method. We have investigated quantitative TLC using staining reagents, in combination with modern image analysis software. Our results show that it is possible to get reliable measurements, suitable for high-throughput screening or physical organic investigations. The range of detection and the errors for the different parts of the process are illustrated. We show that the errors are largely due to the staining process and can be diminished by measuring ratios of compounds. | {
"pile_set_name": "PubMed Abstracts"
} |
Sociopsychological factors affecting the human response to noise exposure.
Community noise is reported to be the most often mentioned undesirable neighborhood condition in a recent U.S. Census survey. Understanding community response to noise involves the measurement of a number of complex acoustic and nonacoustic variables and establishing the chain of relationships between physical exposure, perception, annoyance, and acceptability responses and finally complaint behavior. The perceived loudness of a noise is the most important acoustic parameter influencing annoyance and complaints, and the simple dBA unit can be used to integrate spectral characteristics of complex sounds in community studies. Although energy averaging such as Leq or Ldn can be used to describe multiple noise exposures over time, the variable trade-off relationships between number and level of exposures are somewhat obscured by such summary measures. However, they are still the best available descriptors and, until more accurate ones are developed, can be used to measure community noise environments. Perception of an identical noise exposure can vary according to the physiological noise sensitivity of a person and the activity context in which the noise is heard. Although the acoustic quality of the noise itself usually explains about 10 to 25 per cent of the variability in annoyance responses, sociopsychological variables measured in field studies account for 35 to 50 per cent of the variations in human annoyance responses. Three of the most important nonacoustic factors are the connotative fear effects of the noise signal, the feeling that those responsible for the noise are misfeasant in not reducing the noise, and the feeling that harmful health effects are produced by the noise. When residents report great fear, a high misfeasance, and marked health effects, about 90 per cent report a high annoyance level whether their noise exposure level is above 90 Ldn or 65 to 70 Ldn. In contrast, if the feelings are a low fear level, a low degree of misfeasance, and minimal health effects, only 3 to 10 per cent give high annoyance responses. Complaint behavior, although based on intensity of annoyance, is modified by a number of other sociopsychological factors and often is an unreliable indicator of an environmental problem. | {
"pile_set_name": "PubMed Abstracts"
} |
[Personalized therapy concepts for malignant melanoma].
Metastatic melanoma is commonly regarded as one of the most difficult tumor entities to treat. Up to 2011 no systemic therapy had been able to achieve a prolongation of overall survival in controlled randomized trials. Cytotoxic chemotherapy resulted in objective remission in only a small subgroup of patients. The growing insight into the molecular pathology and the discovery of frequent mutations made it possible to define melanoma subgroups suitable for targeted therapies. In approximately 50% of melanomas activating mutations of the BRAF gene were identified and can be treated with specific inhibitors. Further mutations which can be approached by targeted therapies are found on the c-Kit and NRAS genes. Another promising approach is immunotherapy aimed to activate cytotoxic T cells. A monoclonal antibody directed against CTLA-4 was approved after convincing results in clinical trials and antibodies against PD-1 or PD-L1 are currently under clinical investigation. Through these achievements life prolonging therapies are available for melanoma patients for the first time. | {
"pile_set_name": "PubMed Abstracts"
} |
ERCC polymorphisms and risk of osteosarcoma: a meta-analysis.
The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to evaluate the association between ERCC1 or ERCC2 and osteosarcoma risk by systematic meta-analysis. Relative studies were retrieved from electronic databases without language restriction. The last search was updated on March 2017. Quality assessment was analyzed by the Newcastle-Ottawa Scale (NOS) score, which was recommended by the Agency for Healthcare Research and Quality (AHRQ). Meta-analysis was conducted by R language package (R 3.12). This meta-analysis was performed based on 4 case-control studies that included 1208 cases and 2448 controls. The ERCC2-rs1799793 AA+AC > CC (OR=1.3428, 95% CI=1.0201; 1.7674) had an effect on the risk of osteosarcoma development, whereas, there were no significant associations among the other ERCC SNPs (ERCC1 rs3212986, ERCC1 rs11615, and ERCC2 rs13181) and osteosarcoma. The ERCC2 rs1799793 polymorphism is related to the high risk of osteosarcoma development. | {
"pile_set_name": "PubMed Abstracts"
} |
Bio-based ionic liquid crystalline quaternary ammonium salts: properties and applications.
In the present work, we describe the preparation, properties, and applications of novel ionic liquid crystalline quaternary ammonium salts (QSs) of 3-pentadecylphenol, a bio-based low-cost material derived from cashew nut shell liquid. Amphotropic liquid crystalline phase formation in QSs was characterized using a combination of techniques, such as DSC, PLM, XRD, SEM, and rheology, which revealed the formation of one, two, and three dimensionally ordered mesophases in different length scales. On the basis of these results, a plausible mechanism for the formation of specific modes of packing in various mesophases was proposed. Observation of anisotropic ionic conductivity and electrochemical stability suggests their application as a solid electrolyte. | {
"pile_set_name": "PubMed Abstracts"
} |
The contribution of changes in milk delivery to the prolongation of lactational infertility induced by food restriction or increased litter size.
In rats, the length of lactational anovulation is prolonged when litter size is increased or when the dam is food restricted. In both of these situations the energetic demand on the dam is increased, milk delivery to each pup is reduced, and consequently, patterns of pup suckling may be changed. We investigated the contribution of these factors to the maintenance of lactational anovulation by examining the effect of eliminating milk delivery on the length of lactational diestrus in food restricted and ad lib-fed females nursing litters of 8 pups and in females nursing large (14 pups) and small (6 pups) litters. The results of these studies show that preventing milk delivery neither extends the period of lactational infertility in ad lib-fed females nursing eight pups nor eliminates the effects of increasing litter size on this period. | {
"pile_set_name": "PubMed Abstracts"
} |
Limited reliability of lipid-laden macrophage index restricts its use as a test for pulmonary aspiration: comparison with a simple semiquantitative assay.
The lipid-laden macrophage index (LLMI) is a semiquantitative evaluation of alveolar macrophage lipid content used in diagnosis of pulmonary aspiration. To date, there are no published reports regarding the reliability of LLMI. We sought to evaluate the interobserver and intraobserver variability and validity of LLMI and to compare it to a simpler macrophage lipid content index (LCI). To evaluate reliability we compared both the LLMI and LCI of 26 bronchoalveolar lavage (BAL) specimens from 14 aspirators and 12 non-aspirators on 10 separate occasions by two observers. The ranges of means and standard deviations (SD) of LLMI for observer 1 (Obs 1) were 19-160 (5-31) for aspirators, and 0-48 (0-15) for non-aspirators; and those of observer 2 (Obs 2) were 77-249 (13-33) for aspirators and 47-170 (8-37) for non-aspirators. The ranges of means and SD of LCI for Obs 1 were 2-8 (0-2) for aspirators and 0-4 (0-1) for non-aspirators, compared with 2-9 (0-2) for aspirators and 1-6 (0-2) for non-aspirators for Obs 2. No statistical significance was found between LLMI and LCI by comparing coefficients of variation (CV) in either groups or observers. Poor agreement between the two observers was found using a Bland Altman analysis, with the difference of the two observations mostly exceeding zero and becoming larger as the average of the two observations became bigger. The combined sensitivity, specificity, and positive and negative predictive value (PPV and NPV) for both observers of the LLMI were 57%, 75%, 84%, and 69% and those of LCI were 58%, 92%, 93%, and 69%. We conclude that there is poor reliability for both methods. The LCI is simpler and appears to be at least as good as the LLMI. | {
"pile_set_name": "PubMed Abstracts"
} |
Center-based patient care enhances survival of elderly patients suffering from peripheral arterial disease.
Recent advances in catheter-based intervention in patients with symptomatic peripheral arterial disease (PAD) have halved mortality. Mortality of PAD patients still remains high compared to other clinical forms of atherosclerosis. Intensified patient care might increase adherence to medical management and benefit the survival of PAD patients. Two patient cohorts were compared in a longitudinal prospective follow-up study. 370 PAD patients were included in the intensified center-based vascular medicine group (VMC group) and 332 PAD patients were treated by their usual primary care physician (PCP group). Survival in both groups was compared by Kaplan-Meier and Cox-regression analyses after 5 years. Survival of patients in the VMC group was 90.8% compared to 66% in the PCP group. Thus, survival was improved by 24.9% by center-based care (absolute risk CI: 19-30.7%; 38% relative risk). PCP treatment increased all-cause mortality by a hazard ratio of 3.7 (95% CI: 2.5-5.5; p < .001). Mortality in the VMC group was significantly associated with the non-modifiable risk factors age, C-reactive protein, and nephropathy in multivariable analyses. These data imply that multi-morbid elderly PAD patients still benefit by intensified specialist care compared to the usual primary care setting. KEY MESSAGES Center-based patient care improves survival in patients with peripheral arterial disease; mortality was reduced from 82 to 21 events per 1000 patient-years (rate ratio 0.26). Mortality was related to age (HR 1.46), CRP (HR 1.36), and nephropathy (HR 2.7). A multifactorial approach combining adequate drug prescription, accomplishment of agreed goals and repetitive training to initiate, implement, and persist treatment adaptations was applied. | {
"pile_set_name": "PubMed Abstracts"
} |
An evaluation of bupivacaine for regional nerve block in oral surgery.
Bupivacaine provided profound local anesthesia for the removal of impacted third molars in 49 of 50 patients with a minimum of side effects. The drug provides rapid onset and prolonged duration of anesthesia and has good tissue-penetrating properties. | {
"pile_set_name": "PubMed Abstracts"
} |
Propolis allergy. (I). Origin, properties, usage and literature review.
Propolis or bee-glue, a resinous bee-hive product, is the cause of an increasing number of cases of allergic contact dermatitis. Formerly only observed in bee-keepers, propolis allergy today is mainly seen in individuals who use propolis in bio-cosmetics and self treatment of various diseases. Nearly 200 cases are summarized in an overview, including the first description of 'poplar bud' contact dermatitis from 1887. As practically all flavonoid aglycones and most of the other phenolics present in propolis are identical with the bud secretion of poplars, evidence is given that the poplar bud constituents are responsible for propolis hypersensitivity. | {
"pile_set_name": "PubMed Abstracts"
} |
Laparoscopic splenectomy: operative technique and preliminary report.
A technique of laparoscopic splenectomy was developed on animal models and subsequently applied in two human patients. After creation of a 15 mm Hg pneumoperitoneum, five trocars, two with 12-mm diameters, were introduced into the upper abdomen. The spleen was approached directly by dissection of the gastrosplenic ligament. The short gastric vessels and hilar vessels were individually ligated with metallic clips or a surgical stapler, depending on their size. A plastic bag was then introduced into the abdominal cavity and the spleen slipped inside. An umbilical incision measuring 2 to 3 cm was used for extraction after finger fracture of the spleen. After laboratory experience with seven animals, we used this operation on two patients. The first procedure had to be converted to open surgery because of hemorrhage; the second was successfully performed within 4 h. Knowledge of anatomic variations and meticulous surgical technique are necessary for the successful completion of splenic laparoscopic surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Carotid artery stenting: anatomy of a Medicare coverage decision.
The Centers for Medicare and Medicaid Services has made an important reimbursement decision regarding carotid artery stenting for patients at high risk for carotid endarterectomy surgery. This article will identify the carotid coverage questions and process as a case study of the issues that the Centers and stakeholders can face regarding complex new technologies, as well as the questions for carotid artery stenting and other new technologies that the process raises for your hospital. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of selected diphosphonic acid derivatives used in treatment of osteoporosis. Part I. Complexometric determination of diphosphonic acid derivatives.
The purpose of the study was to develop a simple method for determination of diphosphonic acid derivatives in pharmaceutical preparations used in treatment of osteoporosis: disodium etidronate, disodium clodronate, disodium tiludronate, disodium pamidronate, sodium alendronate. The analysis performed by the visual end point titration method with complexing reagent Th(DCTA) in presence of xylenol orange used the ability of these compounds to form complexes. | {
"pile_set_name": "PubMed Abstracts"
} |
Propionibacterium acnes populations involved in deep pathological samples and their dynamics along the cardiac surgical pathway.
Propionibacterium acnes belongs to the normal skin microbiota, but it is also responsible for acne vulgaris and causes serious infections such as endocarditis and surgical site infections (SSI). The P. acnes population is structured into phylogenetic groups, with phylotype I being associated with acne. Herein, we explore the link between phylotypes and clinical origins in a collection of P. acnes isolated from different body sites, involved in deep infections or healthcare-associated infections (HAI), with particular emphasis on strains from cardiac SSI. Cardiac SSI have been further studied in terms of P. acnes population dynamics during the care pathway. The recA and tly genes phylotypes were compared to hemolytic behavior, susceptibility to antimicrobial agents, and clinical origins. An original approach of recA polymerase chain reaction temporal temperature gel electrophoresis (PCR-TTGE) was developed and applied for the direct identification of P. acnes phylotypes in surgical samples, in order to assess their temporal dynamics during the surgical course. Our results underlined the preferential involvement of IA-2/IB and II phylogroups in HAI and SSI. Unlike IA and II, type IA-2/IB presented a gradual increase with the depth of sampling in the peroperative phase of cardiac surgery. Phylotypes IA and IA-2/IB were both predominant in scar tissues and on postoperative skin, suggesting a specific predisposition to recolonize skin. Particular association of the phylotype IA-2/IB with SSI and its propensity to colonize wounds in cardiac surgery was observed. We assumed that the follow-up of P. acnes phylotypes during pathological processes could give new clues for P. acnes pathogenicity. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes in localization of chosen lectins in gerbil's brain submitted to 3 and 4 minute-long CNS ischemia.
The gerbils brains after 3- and 4-minute-long ischemia caused by bilateral common carotid artery occlusion and 14 days survival were investigated using lectin techniques. Chosen lectins, represented by synthetic plant glycoproteids, which are specifically bound to particular sugar residues (receptors) located on the cell surfaces were examined. Lectins recognizing the following sugar residues have been used in our experiment: 1. N-acetyl-D-galactosyl (using Helix pomatia agg., HPA) 2. alpha-D-mannosyl and alpha-D-glucosyl (using Concanavalin A, Con A). 3. beta-D-galactosyl (using Ricinus communis agg., RCA-120). 4. beta-D-galactosyl and neuraminic acid (using Arachis hypogaea-Peanut agg., PNA). 5. N-acetyl-galactosaminyl and N-acetyl-neuraminic acid (using Wheat germ agg., WGA). Changes in the glycoconjugates localization were found in neurons, glial cells, vessels, white matter fibers or neuropil. They were expressed by the weaking of the reaction with HPA in the hippocampus and white matter comparing to control. Con A receptors were considerably less susceptible to ischemia, though appearance of positively stained glial cells not found in the control group has been observed. Reaction with RCA-120 localized selectively in the network of capillary vessels decreased considerably. Similarly, receptors marked using PNA revealed reduction of staining reaction in white matter as well as in hippocampal interneurons. Using WGA we have also observed that staining reaction was reduced in capillary as well as in neuropil. That lectin indicated additionally strong accumulation of its sugar residues in glial cells appearing as a result of ischemia in particular sectors of hippocampus. The same cells were also Con A positive. The presented results indicate functionally and histochemically perceptible changes taking place in particular CNS elements as a result of short ischemia, expressed by the disturbances in the localization and accumulation of specific sugar residues examined with the use of lectin technique. | {
"pile_set_name": "PubMed Abstracts"
} |
Ultrasound-assisted technique for challenging jejunostomy balloon-tube replacements.
The authors present a case of a 38-year-old man with a 4-hour history of accidental removal of a jejunostomy balloon-tube replacement (PEG-18-BRT-S, Cook Medical Inc., Bloomington, USA). The patient had undergone a direct percutaneous endoscopic jejunostomy (DPEJ) ten months ago, before chemoradiotherapy treatment for an esophageal squamous-cell carcinoma (uT3N2cM0). His past medical condition included alcoholic liver disease and distal gastrectomy from a life-threatening duodenal bleeding ulcer. | {
"pile_set_name": "PubMed Abstracts"
} |
Genotoxic and carcinogenic risk to humans of drug-nitrite interaction products.
The large majority of N-nitroso compounds (NOC) have been found to produce genotoxic effects and to cause tumor development in laboratory animals; four NOC have been classified by the International Agency for Research on Cancer (IARC) as probably and another 15 as possibly carcinogenic to humans. A considerable fraction of drugs are theoretically nitrosatable due to the presence of amine, amide or other groups which by reacting with nitrite in the gastric environment, or even in other sites, can give rise to the formation of NOC, and in some cases other reactive species. This review provides a synthesis of information on the chemistry of NOC formation, the carcinogenic activity of NOC in animals and humans and the inhibitors of nitrosation reactions. It contains information on the drugs which have been tested for the formation of NOC by reaction with nitrite and the genotoxic-carcinogenic effects of their nitrosation products. In an extensive search we have found that 182 drugs, representing a wide variety of chemical structures and therapeutic activities, were examined in various experimental conditions for their ability to react with nitrite, and 173 (95%) of them were found to form NOC or other reactive species. Moreover, 136 drugs were examined in short-term genotoxicity tests and/or in long-term carcinogenesis assays, either in combination with nitrite or using their nitrosation product, in order to establish whether they produce genotoxic and carcinogenic effects; 112 (82.4%) of them have been found to give at least one positive response. The problem of endogenous drug nitrosation is largely unrecognized. Only a small fraction of theoretically nitrosatable drugs have been examined for the possible formation of genotoxic-carcinogenic NOC, guidelines for genotoxicity testing of pharmaceuticals do not indicate the need of performing the appropriate tests, and patients are not informed that the drug-nitrite interaction and the consequent risk can be reduced to a large extent by consuming the nitrosatable drug with ascorbic acid. | {
"pile_set_name": "PubMed Abstracts"
} |
High-performance liquid chromatographic analysis with diode-array detection of bradykinin, neuropeptide K, and substance P in human plasma.
A method is described for the determination of bradykinin, neuropeptide K (NPK), and substance P in patients with atypical carcinoid syndrome. The developed method uses a combination of conventional and solid-phase extraction as well as high-performance liquid chromatographic techniques. A narrow-bore C18 column with ultraviolet detection is used (200 nm). The technique recovers bradykinin at a level of 98%, NPK at 96%, and substance P at 98% (when pure standards are dissolved) at concentration levels relevant to the atypical carcinoid syndrome. In biological samples, the recovery rate of bradykinin, NPK, and substance P drops to 88, 86, and 88% respectively. The overall analysis time is 150 min from receipt of samples. This method proves to be a valuable tool in the identification of neuropeptides and thus the diagnosis of atypical carcinoid syndrome, especially in puzzling cases with nonspecific symptoms. | {
"pile_set_name": "PubMed Abstracts"
} |
On-line kinetic model discrimination for optimized surface plasmon resonance experiments.
In order to improve the throughput of surface plasmon resonance-based biosensors, an on-line iterative optimization algorithm has been presented aiming at reducing experimental time and material consumption without any loss of confidence on kinetic parameters [De Crescenzo (2008) J. Mol Recognit., 21, 256-66.]. This algorithm was based on a simple Langmuirian model to compute the confidence and predict optimal injections. However, this kinetic model is not suitable for all interactions, as it does not include mass transfer limitation that may occur for fast interaction kinetics. If a simple model was to be used when this phenomenon influenced the interactions, kinetic parameters would be biased. On the other hand, we show in this paper that data analysis with a kinetic model including a mass transfer limitation step would lead to longer experiments and poorer confidence if the interactions were simple. So, in this manuscript, we present an on-line model discrimination and optimization approach to increase the throughput of surface plasmon resonance biosensors. | {
"pile_set_name": "PubMed Abstracts"
} |
Risks for preterm delivery and low birth weight are independently increased by severity of maternal anaemia.
To estimate the effect of the severity of maternal anaemia on various perinatal outcomes. A cross-sectional study. Labour Ward, Muhimbili National Hospital, Dar es Salaam, Tanzania. The haemoglobin of eligible pregnant women admitted for delivery between 15 November 2002 and 15 February 2003 was measured. Data on socio-demographic characteristics, iron supplementation, malaria prophylaxis, blood transfusion during current pregnancy, and current and previous pregnancy outcomes were collected and analysed. Anaemia was classified according to the World Health Organization (WHO) standards: normal--Hb > or = 11.0 g/dl; mild--Hb 9.0-10.9 g/dl; moderate--Hb 7.0-8.9 g/dl; and severe--Hb < 7.0 g/dl. Logistic regression analysis was performed to estimate the severity of anaemia. The following outcome measures were used: preterm delivery (<37 weeks), Apgar score, stillbirth, early neonatal death, low birth weight (LBW) (<2500 g) and very low birth weight (VLBW) (<1500 g). A total of 1174 anaemic and 547 non-anaemic women were enrolled. Their median age was 24 years (range 14-46 years) and median parity was 2 (range 0-17). The prevalence of anaemia and severe anaemia was 68% and 5.8%, respectively. The risk of preterm delivery increased significantly with the severity of anaemia, with odds ratios of 1.4, 1.4 and 4.1 respectively for mild, moderate and severe anaemia. The corresponding risks for LBW and VLBW were 1.2 and 1.7, 3.8 and 1.5, and 1.9 and 4.2 respectively. The risks of preterm delivery and LBW increased in proportion to the severity of maternal anaemia. | {
"pile_set_name": "PubMed Abstracts"
} |
Chemical transmission in the sea anemone Nematostella vectensis: A genomic perspective.
The sequencing of the starlet sea anemone (Nematostella vectensis) genome provides opportunities to investigate the function and evolution of genes associated with chemical neurotransmission and hormonal signaling. This is of particular interest because sea anemones are anthozoans, the phylogenetically basal cnidarians least changed from the common ancestors of cnidarians and bilaterian animals, and because cnidarians are considered the most basal metazoans possessing a nervous system. This analysis of the genome has yielded 20 orthologues of enzymes and nicotinic receptors associated with cholinergic function, an even larger number of genes encoding enzymes, receptors and transporters for glutamatergic (28) and GABAergic (34) transmission, and two orthologues of purinergic receptors. Numerous genes encoding enzymes (14), receptors (60) and transporters (5) for aminergic transmission were identified, along with four adenosine-like receptors and one nitric oxide synthase. Diverse neuropeptide and hormone families are also represented, mostly with genes encoding prepropeptides and receptors related to varying closeness to RFamide (17) and tachykinin (14), but also galanin (8), gonadotropin-releasing hormones and vasopressin/oxytocin (5), melanocortins (11), insulin-like peptides (5), glycoprotein hormones (7), and uniquely cnidarian peptide families (44). Surprisingly, no muscarinic acetylcholine receptors were identified and a large number of melatonin-related, but not serotonin, orthologues were found. Phylogenetic tree construction and inspection of multiple sequence alignments reveal how evolutionarily and functionally distant chemical transmitter-related proteins are from those of higher metazoans. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of losartan on pressure overload-induced cardiac gene expression profiling in rats.
1. In the present study, the effects of losartan on myocardial gene expression changes following cardiac hypertrophy were investigated. 2. Male Wistar rats were randomized to receive 5 or 30 mg/kg per day losartan (i.p.) 1 day after suprarenal abdominal aortic constriction. Two weeks later, cardiac morphology and function were recorded with echocardiography and mean arterial central pressure was measured using carotid catheters. Myocardial gene expression was assessed with cDNA microarrays. 3. The ratios of left ventricular weights to bodyweights, the posterior thickness of the left ventricle and mean arterial central pressure were significantly increased by aortic constriction and attenuated by losartan in a dose-related manner. Genes in different functional categories were regulated in pressure overload-induced cardiac hypertrophy and the majority of changes in gene expression were inhibited by losartan in a dose-dependent manner. 4. However, there were still some genes that were unaffected by losartan, even at a higher dose. In contrast, losartan, especially at a lower dose, was able to induce changes in the expression of several additional genes that were unregulated in simple aortic constriction. 5. In conclusion, losartan is able to inhibit pressure overload-induced cardiac hypertrophy, as well as the majority of pressure overload-related changes in gene expression. The genes that remained unaffected or those that were additionally induced by losartan are likely to be new targets for investigation or therapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Assembly of homotrimeric type XXI minicollagen by coexpression of prolyl 4-hydroxylase in stably transfected Drosophila melanogaster S2 cells.
We established stably transfected insect cell lines containing cDNAs encoding the alpha and beta subunits of human prolyl 4-hydroxylase in both Trichoplusia ni and Drosophila melanogaster S2 cells. The expression level and enzymatic activity of recombinant prolyl 4-hydroxylase produced in the Drosophila expression system were significantly higher than those produced in the T. ni system. We further characterized the involvement of prolyl 4-hydroxylase in the assembly of the three alpha chains to form trimeric type XXI minicollagen, which comprises the intact C-terminal non-collagenous (NC1) and collagenous domain (COL1), in the Drosophila system. When minicollagen XXI was stably expressed in Drosophila S2 cells alone, negligible amounts of interchain disulfide-bonded trimers were detected in the culture media. However, minicollagen XXI was secreted as disulfide-bonded homotrimers by coexpression with prolyl 4-hydroxylase in the stably transfected Drosophila S2 cells. Minicollagen XXI coexpressed with prolyl 4-hydroxylase contained sufficient amounts of hydroxyproline to form thermal stable pepsin-resistant triple helices consisting of both interchain and non-interchain disulfide-bonded trimers. These results demonstrate that a sufficient amount of active prolyl 4-hydroxylase is required for the assembly of type XXI collagen triple helices in Drosophila cells and the trimeric assembly is governed by the C-terminal collagenous domain. | {
"pile_set_name": "PubMed Abstracts"
} |
Glutamate 107 in subunit I of the cytochrome bd quinol oxidase from Escherichia coli is protonated and near the heme d/heme b595 binuclear center.
Cytochrome bd is a quinol oxidase from Escherichia coli, which is optimally expressed under microaerophilic growth conditions. The enzyme catalyzes the two-electron oxidation of either ubiquinol or menaquinol in the membrane and scavenges O2 at low concentrations, reducing it to water. Previous work has shown that, although cytochrome bd does not pump protons, turnover is coupled to the generation of a proton motive force. The generation of a proton electrochemical gradient results from the release of protons from the oxidation of quinol to the periplasm and the uptake of protons used to form H2O from the cytoplasm. Because the active site has been shown to be located near the periplasmic side of the membrane, a proton channel must facilitate the delivery of protons from the cytoplasm to the site of water formation. Two conserved glutamic acid residues, E107 and E99, are located in transmembrane helix III in subunit I and have been proposed to form part of this putative proton channel. In the current work, it is shown that mutations in either of these residues results in the loss of quinol oxidase activity and can result in the loss of the two hemes at the active site, hemes d and b595. One mutant, E107Q, while being totally inactive, retains the hemes. Fourier transform infrared (FTIR) redox difference spectroscopy has identified absorption bands from the COOH group of E107. The data show that E107 is protonated at pH 7.6 and that it is perturbed by the reduction of the heme d/heme b595 binuclear center at the active site. In contrast, mutation of an acidic residue known to be at or near the quinol-binding site (E257A) also inactivates the enzyme but has no substantial influence on the FTIR redox difference spectrum. Mutagenesis shows that there are several acidic residues, including E99 and E107 as well as D29 (in CydB), which are important for the assembly or stability of the heme d/heme b595 active site. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional brain networks for sensory maintenance in top-down selective attention to audiovisual inputs.
Sensory maintenance in top-down selective attention to audiovisual inputs involves distributed cortical activations, while the connectivity between the widespread cortical regions has not been well understood. Graph theory has been demonstrated to be a useful tool in the analysis of brain networks. In this study, we used graph theoretical analysis to investigate the functional brain networks for sensory maintenance in top-down selective attention to audiovisual inputs. Electroencephalograms (EEGs) of 30 channels were recorded from 13 young healthy subjects during a passive view task and a top-down intersensory selective attention task. Phase synchronization indices of EEG signals in pair were computed to construct weighted brain networks. We found small-world properties of the brain networks during both passive view state and top-down selective attentional state in α, β, and γ bands. In addition, the significantly increased clustering coefficient and decreased characteristic path length were observed for brain networks during attentional state compared with passive view state in both β band and γ band. Our results suggest that functional brain networks in higher frequency bands, i.e., β band and γ band, are integrated in different ways during attentional state compared with passive view state. | {
"pile_set_name": "PubMed Abstracts"
} |
Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen.
Cross-reactivity with environmental antigens has been postulated as a mechanism responsible for the induction of autoimmune disease. Experimental autoimmune encephalomyelitis is a T cell-mediated autoimmune disease model inducible in susceptible strains of laboratory animals by immunization with protein constituents of myelin. We used myelin proteolipid protein (PLP) peptide 139-151 and its analogues to define motifs to search a protein database for structural homologues of PLP139-151 and identified five peptides derived from microbial Ags that elicit immune responses that cross-react with this self peptide. Exposure of naive SJL mice to the cross-reactive environmental peptides alone was insufficient to induce autoimmune disease even when animals were treated with Ag-nonspecific stimuli (superantigen or LPS). However, immunization of SJL mice with suboptimal doses of PLP139-151 after priming with cross-reactive environmental peptides consistently induced experimental autoimmune encephalomyelitis. Furthermore, T cell lines from mice immunized with cross-reactive environmental peptides and restimulated in vitro with PLP139-151 could induce disease upon transfer into naive recipients. These data suggest that expansion by self Ag is required to break the threshold to autoimmune disease in animals primed with cross-reactive peptides. | {
"pile_set_name": "PubMed Abstracts"
} |
Cooperation between general practitioners and diabetologists and clinical audit improve the management of type 2 diabetic patients.
A programme was set up in the Essonne (France) between 1994 and 1998 to improve the quality of care for Type 2 diabetic patients. A consensus panel of general practitioners and diabetes specialists established guidelines based on the French St. Vincent recommendations. An audit involving 73 volunteer general practitioners (out of 965 in the Essonne) then evaluated compliance with these guidelines. Care and outcome were assessed in 505 (1995) and 604 (1996) Type 2 diabetic patients. The first audit cycle showed that defined standards were not met for several criteria and also revealed a lack of standardisation of HbA1c measurements and delayed intervention when blood glucose control was inadequate. Corrective measures were adopted: cooperative protocols for foot care, prevention of nephropathy and retinopathy, standardisation of HbA1c, and an educational programme at the primary health care level. The second audit cycle showed improvement in foot care (+33.6%), quality (+39.9%), prescription of HbA1c (+11.9%), and control of blood pressure (+11.9%) and blood lipids (+12.8%). The proportion of early interventions in case of inadequate glucose control increased significantly (+10.5%). However, some gaps persisted, mainly regarding screening for complications, diet counselling and patient education. This study shows that cooperation between general practitioners and diabetes specialists is feasible and effective in the context of a district-wide approach, and that it facilitates the adoption of international guidelines by local physicians. A project has been developed to provide structured diabetes care in general practice and better access to specialist services in order to improve the outcome of Type 2 diabetic patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Omalizumab attenuates airway inflammation and interleukin-5 production by mononuclear cells in patients with severe allergic asthma.
Omalizumab, an anti-immunoglobulin E monoclonal antibody, has shown an inhibitory effect on airway inflammation, which may be associated with clinical improvement of severe asthma. This study evaluated changes in airway inflammation and cytokine release by the peripheral blood mononuclear cells (PBMCs) of Japanese patients with severe asthma after administration of omalizumab. Sixteen Japanese patients with severe asthma who were allergic to house-dust mites were enrolled in this study. Eight received omalizumab every 2 or 4 weeks for 16 weeks, and 8 control subjects were treated with conventional drug treatment. Changes in clinical scores for sputum eosinophils and levels of fraction of exhaled nitric oxide (FeNO) were measured at the time of enrollment and at week 16. Cytokines from PBMCs stimulated by house-dust mite (Dermatophagoides farinae) or ionomycin/phorbol myristate acetate (PMA) were measured at baseline and at week 16. In the omalizumab-treated group, decreases in sputum eosinophils and FeNO were observed following treatment. Furthermore, the ex vivo production of interleukin (IL)-5 by PBMCs in response to both mite allergen and ionomycin/PMA decreased significantly. In contrast, interferon (IFN)-γ production was unchanged. There were no changes in any of the parameters observed in the control group. Omalizumab exerts inhibitory effects on airway inflammation in Japanese patients with severe allergic asthma. This treatment attenuates production of IL-5 by PBMCs stimulated with both a specific allergen and a nonspecific activator. Reduction of the Th2 inflammatory cascade likely contributes to clinical benefits; however, further studies are required to clarify these results due to the small sample size in this study. | {
"pile_set_name": "PubMed Abstracts"
} |
Platelet function testing: quality assurance.
Platelet function tests are widely used for the diagnosis of platelet disorders. In recent years there has been increasing interest in the use of platelet function tests to monitor antiplatelet drug therapy. Quality assurance is important to optimize the performance of laboratory assays but it has not been widely applied to platelet function tests. This deficiency likely reflects the need to use freshly collected blood samples for platelet function tests, and the complex, time-consuming nature of some assays such as aggregation studies. Platelet function testing lacks guidelines, is poorly standardized between laboratories, and rarely is evaluated by internal and external quality assurance exercises. The sensitivity, specificity, and diagnostic utility of some newer, simplified assays of platelet function have been evaluated in a range of clinical settings but corresponding quality assurance data for many established as well as emerging platelet function assays are lacking. Quality assurance issues relevant to testing platelet function are reviewed in this article, with a focus on their application to established and to new and emerging tests. | {
"pile_set_name": "PubMed Abstracts"
} |
Possible role of polyamines in the function of brown adipose tissue.
In order to ascertain possible involvement of polyamines in the physiological regulation of brown fat function, effect of temperature acclimation on the polyamine contents of this tissue and effects of polyamines on the noradrenaline-induced thermogenesis is isolated brown adipocytes were investigated in rats. Daily urinary excretion of polyamines measured collectively for spermidine and spermidine per body weight was decreased in heat acclimation and increased in cold acclimation. Polyamine concentrations per fresh weight of brown fat showed extremely low values compared with those of other tissues previously reported. Putrescine and spermidine contents per fat-free dry matter of brown fat were decreased in cold acclimation, but were not affected in heat acclimation. Spermidine and spermine inhibited the noradrenaline-induced thermogenesis of brown adipocytes dose-dependently. These results suggest that polyamines regulate the heat production of brown adipose tissue in an inhibitory way and cold acclimation potentiates heat production of this tissue by reducing polyamine levels. | {
"pile_set_name": "PubMed Abstracts"
} |
The differential effect of low- versus high-frequency random noise stimulation in the treatment of tinnitus.
Tinnitus is the sensation of a ringing, buzzing, roaring or hissing sound in the absence of an external sound. As tinnitus has been related to hyperactivity and synaptic plasticity changes in the central auditory system, invasive and noninvasive neuromodulation methods have been used to interfere with this underlying mechanism to reduce tinnitus loudness and distress. Recently, transcranial random noise stimulation applied over the auditory cortex induced a more pronounced effect on tinnitus loudness than transcranial direct current and alternating current stimulation. We performed tRNS over the temporoparietal cortex in 154 patients with non-pulsatile tinnitus. A total of 119 patients received low-frequency tRNS (lf-tRNS), 19 high-frequency tRNS (hf-tRNS) and 16 whole frequency spectrum tRNS (wf-tRNS). The effect was evaluated by using the numeric rating scale loudness and distress pre- and post-stimulation. This study revealed a significant reduction in tinnitus loudness when lf-tRNS and hf-tRNS were applied as well as a reduction in tinnitus-related distress with lf-tRNS. Moreover, we observed a significantly more pronounced reduction in loudness and distress in pure tone (PT) tinnitus compared to narrow band noise (NBN) tinnitus when hf-tRNS was applied, a difference that could not be obtained with lf-tRNS. Based on these results, tRNS might be a promising treatment option for non-pulsatile tinnitus; however, we cannot yet provide a clear mechanistic explanation for the different results obtained with different types of stimulation, i.e., lf-tRNS, hf-tRNS and wf-tRNS, or with different types of tinnitus, i.e., PT and NBN tinnitus. | {
"pile_set_name": "PubMed Abstracts"
} |
Pharmacologic prevention of microvascular and macrovascular complications in diabetes mellitus: implications of the results of recent clinical trials in type 2 diabetes.
Observational epidemiologic data indicate that lower blood glucose levels, blood pressure (BP), and lipid parameters are associated with a lower incidence of micro- and macrovascular complications in people with diabetes. While no threshold for this effect is discernible in these observational studies, intervention studies do not mirror this finding. The earliest glycemia target study in type 2 diabetes mellitus, UKPDS, demonstrated unequivocal benefits of tight glucose control on microvascular complications, but needed a prolonged follow-up to demonstrate a benefit on macrovascular outcomes and mortality. Recently, three major studies, ACCORD, ADVANCE, and VADT, evaluated the impact of attaining euglycemia (ACCORD) or near-euglycemia (ADVANCE, VADT) in older patients with diabetes and high cardiovascular (CV) risk. None of these studies, either individually or on pooled analysis, demonstrated any reduction in all-cause or CV mortality, although the meta-analyses revealed 15-17% reductions in the incidence of non-fatal myocardial infarction in those exposed to tight glucose control. A higher mortality was observed in the intensive glucose control arm of ACCORD, resulting in the premature termination of the glucose-lowering component of this study. Also, the occurrence of hypoglycemic episodes (total and major) was significantly higher in the intensive glucose control arm. ADVANCE and ACCORD also had BP-lowering components. While data from ADVANCE demonstrated a benefit of routine use of a combination of perindopril and indapamide, with a decline in all-cause mortality, CV mortality, and new-onset microalbuminuria, reducing systolic BP to <120 mmHg in ACCORD did not result in any incremental benefits over a systolic BP<140 mmHg. A residual CV risk observed in people with diabetes even after low-density lipoprotein (LDL) cholesterol lowering has led to trials evaluating additional therapy with fibric acid derivatives to reduce triglyceride levels. The lipid-lowering arm of ACCORD failed to demonstrate any benefit of add-on therapy with fibric acid derivatives to LDL-lowering treatment with HMG-CoA reductase inhibitors (statins) on vascular outcomes in patients with diabetes. However, data from earlier studies, and also from the subgroup analysis of ACCORD, indicate a probable benefit of adding treatment with fibric acid derivatives to individuals with persistently elevated triglyceride levels despite statin therapy. The most compelling evidence comes from studies assessing the impact of multiple risk factors - glucose, BP, and cholesterol. Studies like the Steno study unequivocally demonstrate the benefit of aggressive control of all three parameters on vascular outcomes in patients with diabetes. In conclusion, attempts to achieve euglycemia in older patients with type 2 diabetes with co-morbidities are not associated with any survival benefit, but may reduce the occurrence of non-fatal CV events. There is a significant risk of major hypoglycemia with this approach, thereby probably limiting its utility to younger patients with new-onset disease. Similarly, lowering systolic BP below 120 mmHg in high CV risk people with diabetes is associated with significant excess adverse events, limiting the utility of such an intervention. However, a clear benefit, which is also cost effective, is observed with strategies for multiple risk-factor control, which should be universally adopted in clinical practice. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of chronic trifluoperazine administration and subsequent withdrawal on the production and persistence of perioral behaviours in two rat strains.
The effect of chronic administration of trifluoperazine on the perioral movement profile of Wistar and Sprague-Dawley rats was examined. Perioral movements were characterised by visual observations, coupled with electromyographic recording from the masseter muscle. In drug-naive animals from both strains the spectrum of perioral behaviours was essentially identical, primarily consisting of purposeless chewing, accompanied by occasional bursts of facial tremor and teeth chattering, with occasional yawning. Each burst of facial tremor was accompanied by a transient increase in the rate of purposeless chewing. Wistar rats exhibited a higher level of spontaneous purposeless chewing compared to Sprague-Dawley rats. In both strains, chronic administration of trifluoperazine (5 mg/kg per day, PO) for 5 months induced an increase in perioral behaviour, which primarily consisted of enhanced purposeless chewing. In Wistar rats the drug-induced increase in purposeless chewing was accompanied by an increase in the incidence of yawning, with no change in the incidence of either facial tremor or teeth chattering. In contrast, Sprague-Dawley rats displayed a drug-induced increase in purposeless chewing, accompanied by an increase in the incidence of facial tremor and teeth chattering, but not yawning. In Wistar rats withdrawal of trifluoperazine diminished but did not reverse the drug-induced increase in purposeless chewing. Drug withdrawal also precipitated a transient increase in the incidence of facial tremor and teeth chattering, but had no effect on yawning. In Wistar rats, the level of purposeless chewing and the incidence of yawning remained elevated above control levels for at least 13 weeks after drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Lyme borreliosis.
Lyme borreliosis is a multi-organ infection caused by spirochetes of the Borrelia burgdorferi sensu lato group with its species B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, which are transmitted by ticks of the species Ixodes. Laboratory testing of Lyme borreliosis includes culture, antibody detection using ELISA with whole extracts or recombinant chimeric borrelia proteins, immunoblot, and PCR with different levels of sensitivity and specificity for each test. Common skin manifestations of Lyme borreliosis include erythema migrans, lymphocytoma, and acrodermatitis chronica atrophicans. The last two conditions are usually caused by B garinii and B afzelii, respectively, which are seen more frequently in Europe than in America. Late extracutaneous manifestations of Lyme borreliosis are characterised by carditis, neuroborreliosis, and arthritis. We present evidence-based treatment recommendations for Lyme borreliosis and review the prevention of Lyme borreliosis, including the Lyme vaccines. | {
"pile_set_name": "PubMed Abstracts"
} |
Xylem embolism and drought-induced stomatal closure in maize.
Water relations during drought and xylem vulnerability to embolism were studied on four maize ( Zea mays L.) genotypes having contrasting grain yields under drought conditions. Drought provoked a drop in xylem pressure, leaf water potential and whole-plant transpiration. Transpiration was reduced to a minimum value when xylem pressures reached ca. -1.6 MPa. This value corresponded to the threshold xylem pressure below which xylem embolism developed to a substantial degree in leaf midribs. Therefore, xylem embolism always remained low in leaf veins, even when plants exhibited clear water-stress symptoms. This suggests that stomatal closure during drought contains xylem embolism to a minimum value. Cavitation resistance was not related to grain yield under drought conditions for the four genotypes evaluated. However, it can be speculated that an increase in cavitation resistance by cultural practices or genetic selection may increase drought survival in maize. | {
"pile_set_name": "PubMed Abstracts"
} |
Differences in the nonreducing ends of heparan sulfates excreted by patients with mucopolysaccharidoses revealed by bacterial heparitinases: a new tool for structural studies and differential diagnosis of Sanfilippo's and Hunter's syndromes.
Enzymatic and chemical analyses of the structures of heparan sulfates excreted in the urine by patients with Sanfilippo's and Hunter's syndromes revealed that their nonreducing ends differ from each other and reflect the enzyme deficiency of the syndromes. The heparan sulfates from the different syndromes were treated with heparitinase II, crude enzyme extracts from Flavobacterium heparinum, and nitrous acid degradation. The heparan sulfates from patients with Sanfilippo A (deficient in heparan N-sulfatase) and Sanfilippo B (deficient in alpha-N-acetylglucosaminidase) were degraded with heparitinase II producing, besides unsaturated disaccharides, substantial amounts of glucosamine N-sulfate and N-acetylglucosamine, respectively. The heparan sulfate from patients with Hunter's syndrome (deficient in iduronate sulfatase) were degraded by heparitinase II or crude enzyme extracts to several products, including two saturated disaccharides containing a sulfated uronic acid at their nonreducing ends. The heparan sulfate from patients with Sanfilippo's C syndrome (deficient in acetyl Co-A: alpha-glucosaminide acetyltransferase) produced, by action of heparitinase II, among other products, two sulfated trisaccharides containing glucosamine with a nonsubstituted amino group. In addition to providing a new tool for the differential diagnosis of the mucopolysaccharidoses, these results bring new insights into the specificity of the heparitinases from Flavobacterium heparinum. | {
"pile_set_name": "PubMed Abstracts"
} |
Liver regeneration in partially hepatectomized rats infused with carnitine and lipids.
Male Wistar rats were subjected to 65-70% hepatectomy. Immediately after surgery a 6-hour infusion was given containing 115 kJ/kg b.w. of long-chain fatty acids (Nutralipid Spofa) (N) or N combined with L-carnitine (Carnitene Sigma Tau) in doses 8 mg (12.4 mumol), 40 mg (62 mumol) and 200 mg (310 mumol)/kg b.w. The rats were killed 6, 18, 21, 24 and 30 h after surgery. The results of our study demonstrate that infusion of lipids combined with carnitine, has a stimulating dose-dependent effect on liver regeneration in partially hepatectomized rats, excluding the low dose of carnitine--8 mg/kg. The dose of carnitine of 40 mg/kg had the highest stimulating effect on the course of the liver DNA synthesis, culminating 21 h after partial hepatectomy. Later, 24 and 30 h after hepatectomy, the mitotic activity of hepatocytes was highest in rats infused with carnitine in doses of 200 mg/kg b.w. | {
"pile_set_name": "PubMed Abstracts"
} |
Work- and nonwork-related factors associated with PACU nurses' fatigue.
The purpose of this study was to describe postanesthesia care unit (PACU) nurses' fatigue and link fatigue levels to work- and nonwork-related factors. The study design is a pilot study using a descriptive correlation design. Participants used a 4-week daily diary to record hours worked, breaks taken, and sleep patterns and completed the Occupational Fatigue Exhaustion Recovery Scale (OFER). The sample included 20 experienced (17.3 ± 9.5 years) nurses. Only 4% reported no breaks during their shift. Median sleep time was 6 hours 40 minutes. OFER scores were acute fatigue (66.5 ± 19.3), intershift fatigue (52 ± 18.6), and chronic fatigue (35.7 ± 17.2). In conclusion, acute fatigue scores reflect the challenges of working in the PACU. Despite high acute fatigue scores, intershift fatigue scores reflected recovery and chronic fatigue scores were low. Fatigue reduction strategies may account for these results including processes to ensure breaks are taken, use of a flex shift nurse to prevent shift overruns, and reduction of the number of three consecutive 12-hour shifts. | {
"pile_set_name": "PubMed Abstracts"
} |
Migraine and haemostasis.
Migraine is a risk factor for cerebral infarction in young women. The nature of the connection between these diseases remains however essentially unknown. Abnormalities of haemostasis leading to an increased thrombotic risk would provide a logical link. Platelets, antiphospholipid antibodies and more recently congenital thrombophilia have thus successively been implicated. The different studies concerning these topics have been reviewed. Because of the conflicting results obtained and because of the numerous methodological shortcomings of many of these studies, no definite conclusion can be reached. It is possible that these 3 factors play a role in the ischemic risk of migraine, but it is as likely or even more likely that other factors (inside or outside the hemostatic system) play a more important role. Further studies are thus deeply needed. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical analysis of tamoxifen, an anti-neoplastic agent, in plasma.
Tamoxifen, a phenylstilbene derivative, is currently being used to treat metastatic breast cancer. We describe an analytical method for monitoring the parent drug and its 4-hydroxylated derivative in whole blood and plasma. After extraction from biological media, the analytes are converted to highly fluorescent products by ultraviolet irradiation, and then separated by liquid-chromatography on a muBondapak CN column, with spectrofluorometric detection of components. Detection limits for tamoxifen and its 4-hydroxy derivative are 1 and 2 microgram/liter of biological fluid, respectively. Conditions have been optimized so that the reaction proceeds fast enough for convenient sample handling without jeopardizing fluorescence yield due to the photocatalyzed degradation of the fluorescent product. Evidence suggests that the fluorophore being monitored is a phenanthrene derivative. | {
"pile_set_name": "PubMed Abstracts"
} |
Remembering Bruce: the early years.
This paper summarizes Merrifield-Stewart interactions during the years 1952-1968. | {
"pile_set_name": "PubMed Abstracts"
} |
MSE for Label-Free Absolute Protein Quantification in Complex Proteomes.
Label-free peptide quantification is a promising approach for the large-scale characterization of proteome dynamics at low cost. Here, we describe a method for absolute label-free quantification using an untargeted approach for peptide fragmentation referred to as MSE. We show that spiked external standards provide sufficient accuracy for the quantification of proteins in complex samples resulting in similar protein quantification results as spectral counting. As an advantage, label-free quantification also works for small numbers of samples whereas spectral counting requires large datasets to result in a similar robustness. The sensitivity of protein identification increases significantly when ion mobility separation is included in addition to the standard LC-MS setup in the analysis workflow. Ion mobility decreases sample complexity and serves as an additional separation criterion to align a parent ion with its product ions after MSE fragmentation. As a drawback, quantification of high abundance proteins becomes inaccurate because of detector saturation. We describe here a suitable workflow to achieve good sensitivity for protein quantification and give initial guidance on data interpretation. To achieve good identification and quantification accuracy, the protein amount loaded onto the column should not exceed 400-600 ng. In a dynamic range window of 3-4 orders of magnitude, robust quantification can be obtained with complex samples comprising up to 2000-3000 proteins. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors associated with the functional capacity of older adults with leprosy.
to investigate the association between socio-demographic and clinical factors and the functional capacity of older adults with leprosy. cross-sectional analytical study conducted in Fortaleza, Ceará, Brazil, with 77 older adult patients with leprosy in a referral service, through interview, medical records and application of the Katz Index and the Lawton and Brody Scale. the mean age was 68.23 years, with prevalence of men, in stable union/married, with mean monthly family income of 2.04 minimum wages, positive bacillary index, clinical dimorphic form and grade zero disability. In the Lawton and Brody scale, independence (58.5%) was predominant and associated to the variables "living arrangement" and "educational attainment". Total independence (87.0%) was predominant in the Katz Index and statistically associated to the variable monthly family income. most of the participants were classified as independent in the instruments used. Furthermore, the instruments pointed to a greater number of associations with socio-demographic and clinical factors not related to leprosy. investigar a associação de fatores sociodemográficos e clínicos à capacidade funcional de idosos com hanseníase. estudo transversal, analítico realizado em Fortaleza, Ceará, com 77 idosos com hanseníase acompanhados em serviço de referência, através de entrevista, consulta ao prontuário e aplicação do Índice de Katz e Escala de Lawton e Brody. a média de idade foi de 68,23 anos, com prevalência de sexo masculino, união estável/casado, renda familiar mensal média de 2,04 salários mínimos, índice baciloscópico positivo, forma clínica dimorfa e Grau de Incapacidade Física zero. Na escala de Lawton e Brody prevaleceu a independência (58,5%) com associação às variáveis "com quem reside" e "escolaridade". Destacou-se a independência total (87,0%) no índice de Katz, associando-se estatisticamente a variável renda familiar mensal. a maioria dos participantes mostrou-se independente nos instrumentos utilizados. Ademais, os instrumentos apontaram mais associações a fatores sociodemográficos e clínicos não relacionados com a hanseníase. | {
"pile_set_name": "PubMed Abstracts"
} |
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