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Improved Sealing and Remineralization at the Resin-Dentin Interface After Phosphoric Acid Etching and Load Cycling. The purpose of this study was to investigate micro-morphology of the resin-dentin inter-diffusion zone using two different single-bottle self-etching dentin adhesives with and without previous acid-etching, after in vitro mechanical loading stimuli. Extracted human third molars were sectioned to obtain dentin surfaces. Two different single-bottle self-etching dentin adhesives, Futurabond U and Experimental both from VOCO, were applied following the manufacturer's instructions or after 37% phosphoric acid application. Resin-dentin interfaces were analyzed with dye assisted confocal microscopy evaluation (CLSM), including the calcium-chelation technique, xylenol orange (CLSM-XO). CLSM revealed that resin-dentin interfaces of unloaded specimens were deficiently resin-hybridized, in general. These samples showed a Rhodamine B-labeled hybrid complex and adhesive layer completely affected by fluorescein penetration (nanoleakage) through the porous resin-dentin interface, but thicker after PA-etching. Load cycling promoted an improved sealing of the resin-dentin interface at dentin, a decrease of the hybrid complex porosity, and an increment of dentin mineralization. Load cycled specimens treated with the XO technique produced a clearly outlined fluorescence due to consistent Ca-mineral deposits within the bonding interface and inside the dentinal tubules, especially when the experimental adhesive was applied.
{ "pile_set_name": "PubMed Abstracts" }
Decoding calcium signals by multifunctional CaM kinase. Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is one of the three major protein kinases coordinating cellular responses to hormones and neurotransmitters. It mediates the action of Ca2+ on neurotransmitter synthesis and release, on carbohydrate metabolism and on the cytoskeleton. CaM kinase has structural/functional properties that facilitate its response to distinctive attributes of Ca2+ signals which often involve transient increases that span a narrow concentration range and increases that are pulsatile rather than persistent. The kinase responds to the narrow working range of Ca2+ signals by the use of calmodulin as the Ca2+ sensor. It is activated by the binding of calmodulin to an autoinhibitory domain that keeps the kinase inactive in the basal state. The transient nature of the signal is accommodated by autophosphorylation of this autoinhibitory domain which allows the kinase to remain partially active after calmodulin dissociates and thereby switches it to a Ca(2+)-independent species. The pulsatile nature of Ca2+ signals may also be decoded by CaM kinase. Autophosphorylation traps calmodulin on autophosphorylated subunits by greatly reducing its off-rate. At high frequency of stimulation, calmodulin would remain trapped during the brief interval between Ca2+ oscillations and each successive rise in Ca2+ would recruit more calmodulin. This may enable a stimulus frequency dependent activation of CaM kinase.
{ "pile_set_name": "PubMed Abstracts" }
Novel pH-responsive polymeric micelles prepared through self-assembly of amphiphilic block copolymer with poly-4-vinylpyridine block synthesized by mechanochemical solid-state polymerization. We fabricated polymeric micelles containing 5-fluorouracil (5-FU) or fluorescein using the amphiphilic block copolymer, poly-4-vinylpyridine-b-6-O-methacryloyl galactopyranose. Although the polymeric micelles were stable at pH 7.4, they readily decomposed at pH 5, resulting in near complete release of 5-FU. Uptake of polymeric micelles containing fluorescein by HepG2 and HCT116 cells was also investigated. With both cell types, strong fluorescence was observed after a 12-h incubation, but the fluorescence weakened after 24 h of incubation. The fluorescein incorporated into the polymeric micelles was released into acidic organelles (endosome and/or lysosome), from which it diffused throughout the cell. The cytotoxicity of polymeric micelles containing 5-FU was evaluated against HepG2 cells using a CCK-8 assay. The results suggest that polymeric micelles containing 5-FU are more cytotoxic to HepG2 cells than free 5-FU.
{ "pile_set_name": "PubMed Abstracts" }
Calcium transport by the proximal tubule. Taken together the results of these in vivo microperfusion experiments indicate that calcium absorption by the proximal tubule depends on more than one transport mechanism. We have observed that net calcium flux is affected by changes in calcium ion activity (even with constant total calcium concentration) and in transepithelial voltage. This sensitivity of calcium flux to changes in electrochemical driving force points to a diffusional component of calcium transport. Ng et al. (1984) have recently concluded that simple diffusion accounts for the majority of calcium absorption by superficial proximal convoluted tubules of the rabbit. The pathway for this diffusional component may involve paracellular channels. The permeability of this pathway appears to be as high for calcium as it is for sodium, potassium and chloride. Calcium flux is also affected by changes in osmotic water flow. The effect of changes in volume flow on calcium transport occurs even in the absence of concentration changes in bulk solutions. Thus, it does not appear to be the result of changes in passive driving forces secondary to dilution or concentration of tubule fluid. At present we are not able to distinguish between two other possible mechanisms: solute polarization in a microscopic unstirred fluid layer adjacent to the cell membrane, or true entrainment of calcium in the stream of osmotically driven water flow (solvent drag). Either mechanism could provide an additional component of total calcium transport independent of changes in bulk phase ion concentrations and electrical driving forces. A third component of total calcium absorption appears to involve active transport.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
Stimulation of growth hormone release in dwarf and normal chickens by thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF). The effect of thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF) on growth hormone (GH) release was studied in both dwarf and normal Rhode Island Red chickens with a similar genotype except for a sex-linked dw gene. Both TRH (10 micrograms/kg) and hpGRF (20 micrograms/kg) injections stimulated plasma GH release within 15 min in young and adult chickens. The increase in GH release was higher in young cockerels than that in adult chickens. The age-related decline in the response to TRH stimulation was observed in both strains, while hpGRF was a still potent GH-releaser in adult chickens. The maximal and long acting response was observed in young dwarf chickens, suggesting differences in GH pools releasable by TRH and GRF in the anterior pituitary gland. The pituitary gland was stimulated directly by perifusion with hpGRF (1 microgram/ml and 10 micrograms/ml) or TRH (1 microgram/ml). Repeated perifusion of GRF at 40 min intervals blunted further increase in GH release, but successive perifusion with TRH stimulated GH release. The results suggest the possibility that desensitization to the effects of hpGRF occurs in vitro and that the extent of response depends on the number of receptors for hpGRF or TRH and/or the amount of GH stored in the pituitary gland.
{ "pile_set_name": "PubMed Abstracts" }
Molecular pathways: regulation of metabolism by RB. The discovery of the retinoblastoma (RB-1) gene as a tumor suppressor that is disrupted in a majority of human cancers either via direct or indirect genetic alterations has resulted in increased interest in its functions and downstream effectors. Although the canonical pathway that links this tumor suppressor to human cancers details its interaction with the E2F transcription factors and cell-cycle progression, recent studies have shown an essential role for RB-1 in the suppression of glycolytic and glutaminolytic metabolism. Characterization of the precise metabolic transporters and enzymes suppressed by the RB-E2F axis should enable the identification of small molecule antagonists that have selective and potent antitumor properties.
{ "pile_set_name": "PubMed Abstracts" }
Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Early studies of liver resection for colorectal cancer metastases identified patients with concomitant extrahepatic disease as a group with poor outcomes. These studies concluded that the presence of extrahepatic disease should be a contraindication to resection. This contraindication has more recently been challenged. In this paper, we review the published work on metastatic colorectal cancer, pertaining to the role of surgery in patients with liver metastases and concomitant extrahepatic disease. 5-year survival after resection is worse in patients with extrahepatic disease than in patients with liver-only disease, but is similar to that seen in patients who underwent resection in the era before the use of modern chemotherapy. Recurrence occurs in most patients. There is a role for surgery in highly selected patients with single sites of extrahepatic disease, although expectations should be different than those of patients with liver-only metastases. Further studies are necessary to define the patient group best suited for resection of hepatic metastases with extrahepatic disease.
{ "pile_set_name": "PubMed Abstracts" }
Evaluation of Three Commercial Handheld Ultra-Low-Volume Foggers with Aqualure® 20-20 Against Adult Aedes albopictus. The Anastasia Mosquito Control District (AMCD) tests all equipment before field use to determine if machines are suitable for the needs of the district. Three handheld ultra-low-volume (ULV) foggers--the American LongRay (ULV) Fogger Model 3600B with rechargeable lithium battery (DC model), American LongRay ULV Fogger Model 3600E with 110V or 220V AC power (AC model), and Boston Fog Battery Motorized Fogger (Boston Fogger)--were compared to determine which fogger would be most suitable for use by AMCD. Mortality of caged Aedes albopictus was analyzed after 24 h to determine the success of a single application. All 3 foggers resulted in 100% mortality after 24 h using the insecticide Aqualuer 20-20 (active ingredients permethrin 20.6% and piperonyl butoxide 20.6%) 1:5 dilution with reverse osmosis water. Based on operator safety, robustness, and operational performance, the American LongRay DC model was found to be the most suitable at administering Aqualuer 20-20 against caged adult Ae. albopictus.
{ "pile_set_name": "PubMed Abstracts" }
Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Most actions of glucocorticoids (GCs) are mediated by the glucocorticoid receptor (GR). The interindividual response to GCs varies considerably, as demonstrated by a variable suppressive response to 0.25-mg dexamethasone (DEX). Several polymorphisms in the gene coding for the GR have been described. It is unclear to what extent the observed response variability is due to GR polymorphisms or to other factors. However, at least three polymorphisms seem to be associated with altered GC sensitivity and changes in body composition and metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to GCs, increased insulin response to DEX, a tendency towards lower bone mineral density, and increased body mass index (BMI). However, other reports found no associations with BMI. Another polymorphism, previously described as a BclI restriction fragment length polymorphism, recently was identified as a C --> G nucleotide change. The G allele also was associated with increased sensitivity to GCs. In middle-aged subjects, the G allele of this BclI polymorphism was associated with increased abdominal obesity, while at older age, a lower BMI was found, accompanied by a tendency towards lower lean body mass. A third polymorphism consists of two linked, single-nucleotide mutations in codons 22 and 23, of which the second mutation results in an amino acid change from arginine (R) to lysine (K). In contrast to the other polymorphisms, this ER22/23EK polymorphism was associated with a relative resistance to GCs. In line with this, ER22/23EK carriers had lower total cholesterol and low-density lipoprotein cholesterol levels as well as lower fasting insulin concentrations and a better insulin sensitivity. C-reactive protein levels were lower in ER22/23EK carriers, as was found in a different population of elderly males. In accordance with this healthy metabolic profile, we found in this population a significantly better survival in ER22/23EK carriers after a 4-year follow-up. GCs also affect the brain. Although a certain level of cortisol is essential for proper brain functioning, excessive GC levels have been shown to negatively affect brain morphology and functions. At older age, we found that the risk of dementia and white matter lesions was lower in ER22/23EK carriers. GCs are also important in the regulation of body fat distribution. At young age, we observed sex-specific differences in body composition. Male ER22/23EK carriers were taller, had more muscle mass, and were stronger than noncarriers. In young females, ER22/23EK carriers had tendencies towards smaller waist and hip circumferences and lower body weight. Another polymorphism (TthIIII) was not associated with altered GC sensitivity. In conclusion, these polymorphisms in the GR gene may contribute considerably to the observed variability in GC sensitivity. As a result, they are associated with several differences in body composition and metabolic factors.
{ "pile_set_name": "PubMed Abstracts" }
Developing the random phase approximation into a practical post-Kohn-Sham correlation model. The random phase approximation (RPA) to the density functional correlation energy systematically improves upon many limitations of present semilocal functionals, but was considered too computationally expensive for widespread use in the past. Here a physically appealing reformulation of the RPA correlation model is developed that substantially reduces its computational complexity. The density functional RPA correlation energy is shown to equal one-half times the difference of all RPA electronic excitation energies computed at full and first order coupling. Thus, the RPA correlation energy may be considered as a difference of electronic zero point vibrational energies, where each eigenmode corresponds to an electronic excitation. This surprisingly simple result is intimately related to plasma theories of electron correlation. Differences to electron pair correlation models underlying popular correlated wave function methods are discussed. The RPA correlation energy is further transformed into an explicit functional of the Kohn-Sham orbitals. The only nontrivial ingredient to this functional is the sign function of the response operator. A stable iterative algorithm to evaluate this sign function based on the Newton-Schulz iteration is presented. Integral direct implementations scale as the fifth power of the system size, similar to second order Moller-Plesset calculations. With these improvements, RPA may become the long-sought robust and efficient zero order post-Kohn-Sham correlation model.
{ "pile_set_name": "PubMed Abstracts" }
Peroxisome proliferator-activated receptor gamma (PPARγ) agonist fails to overcome trans-10, cis-12 conjugated linoleic acid (CLA) inhibition of milk fat in dairy sheep. The trans-10, cis-12 conjugated linoleic acid (CLA) causes milk fat depression by downregulating expression of genes and transcription factors involved in lipogenesis and it has been proposed that peroxisome proliferator-activated receptor gamma (PPARγ) can be inhibited by trans-10, cis-12 CLA. The PPARγ is a nuclear receptor activated by natural or synthetic ligands and promotes expression of lipogenic genes and its effect on mammary lipogenesis and the interaction with trans-10, cis-12 CLA in lactating ewes was evaluated using thiazolidinedione (TZD), a chemical PPARγ agonist. A total of 24 lactating ewes were randomly assigned to one of the following treatments for 7 days: (1) Control (5 ml/day of saline solution); (2) TZD (4 mg/kg of BW/day in 5 ml of saline solution); (3) CLA (27 g/day with 29.9% of trans-10, cis-12); (4) TZD+CLA. Compared with Control, milk fat content was not changed by TZD, but was decreased 22.3% and 20.5% by CLA and TZD+CLA treatments. In the mammary gland, TZD increased PPARγ gene expression by 174.8% and 207.8% compared with Control and TZD+CLA treatments, respectively. Conjugated linoleic acid reduced sterol regulatory element-binding transcription protein 1 (SREBP1) gene expression 89.2% and 75.3% compared with Control and TZD+CLA, respectively, demonstrating that TZD fails to overcome CLA inhibition of SREBP1 signaling. In adipose tissue, the expression of SREBP1 and stearoyl CoA desaturase 1 (SCD1) genes were increased by the TZD+CLA treatment, compared with the other treatments. Conjugated linoleic acid decreased milk fat concentration and expression of lipogenic genes, while TZD had no effect on milk fat concentration, expression of lipogenic enzymes or regulators in the mammary gland and failed to overcome the inhibition of these by CLA. Therefore, CLA inhibition of milk fat synthesis was independent of the PPARγ pathway in lactating dairy ewes.
{ "pile_set_name": "PubMed Abstracts" }
Cytophotometric assessment of T-2 toxin induced alterations in azure B-RNA and Coomassie-protein in supraoptic-magnocellular neurons of rat hypothalami. Quantitative cytophotometry was used to monitor T-2 toxin-induced alterations in azure B-RNA and Coomassie-total cell protein in supraoptic-magnocellular neurons of rat hypothalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.00 and 1.50 x LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric azure B-RNA and Coomassie-protein staining of brain sections, scanning-integrating microdensitometry was used to quantify toxin-induced alterations in these well established indices of neuronal toxicity. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in azure B-RNA reactivity were observed in the 0.75, 1.00 and 1.50 x LD50 groups (i.e. 11%, 13% and 8%, respectively); no differences in RNA levels were observed between controls and the 0.50 x LD50 group. In addition, a decrease in Coomassie-total cell protein was seen in animals receiving 0.50, 0.75 and 1.50 x LD50 T-2 toxin (i.e. 33%, 21% and 12%, respectively); however, toxin administration did not alter protein levels in the 1.00 x LD50 group. Furthermore, a dose-dependent decrease in systolic blood pressure was observed at 8 hr. post-injections (i.e., approximately -39%, -52%, -66% and -64% for the 0.50, 0.75, 1.00 and 1.50 x LD50 groups, respectively). Additional observations include pronounced polydipsia, ascites, abdominal and subdural hemorrhage, and horripilation (piloerection) in experimental groups. It is postulated that the T-2 toxin-induced reductions in azure B-RNA and Coomassie-protein represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is advanced that the supraoptic-magnocellular compartment represents an important site in T-2 toxin mycotoxicosis. Moreover, these findings support previous claims that T-2 toxin intoxication may critically impair the vasopressinergic response to toxin-induced cardiovascular collapse.
{ "pile_set_name": "PubMed Abstracts" }
Long-term potentiation in dentate gyrus of the rat is inhibited by the phosphoinositide 3-kinase inhibitor, wortmannin. The pivotal role of inositol phospholipids in cell signalling has been placed centre-stage again with the recognition that phosphoinositide (PI) 3-kinase is implicated in several cellular processes. Stimulation of PI-3 kinase requires activation of the 85 kD regulatory subunit which relies on tyrosine phosphorylation, one consequence of which is activation of the 110 kD catalytic subunit. In this study, we have investigated the role of PI 3-kinase in the expression of long-term potentiation (LTP) in perforant path-granule cell synapses of the rat. We report that intracerebroventricular injection of wortmannin inhibited expression of LTP, though it did not affect the early change in the synaptic response. Activation of PI 3-kinase was enhanced in tetanized tissue prepared from dentate gyrus, compared with untetanized tissue, but this effect was inhibited in tissue prepared from wortmannin-pretreated rats. LTP was associated with increased glutamate release, as previously described, but this effect was also inhibited in tissue prepared from wortmannin-pretreated rats. The results presented demonstrate that wortmannin also exerted an inhibitory effect on KCl-stimulated glutamate release and calcium influx in hippocampal synaptosomes in vitro. The evidence presented is consistent with the hypothesis that PI 3-kinase activation, possibly by NGF, plays a role in expression of LTP in dentate gyrus.
{ "pile_set_name": "PubMed Abstracts" }
Evidence for localization of biologically active recombinant retroviral vector to lymph nodes in mice injected intramuscularly. We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes primarily to the site of injection. In this study, we have investigated more extensively the localization and biological activity of HIV-IT(V) administered intramuscularly to female mice. Consistent with our previous findings, retroviral DNA was detected by PCR at the site of injection. Retroviral DNA was also detected in proximal lymph nodes, a tissue not examined previously. Potential for drainage of vector particles to regional lymph nodes was indicated by experiments showing that intramuscular injection of fluorescein-labeled latex beads concentrated in the regional lymph nodes in mice. The localization of retroviral DNA to the injection site and regional lymph nodes may play a role in the induction of the HIV-specific CTL responses detected in splenocyte populations isolated from mice 21 days after injection with HIV-IT(V).
{ "pile_set_name": "PubMed Abstracts" }
Confined quantum time of arrivals. We show that formulating the quantum time of arrival problem in a segment of the real line suggests rephrasing the quantum time of arrival problem to finding states that evolve to unitarily collapse at a given point at a definite time. For the spatially confined particle, we show that the problem admits a solution in the form of an eigenvalue problem of a compact and self-adjoint time of arrival operator derived by a quantization of the classical time of arrival, which is canonically conjugate with the Hamiltonian in a closed subspace of the Hilbert space.
{ "pile_set_name": "PubMed Abstracts" }
Thermally induced delay and reversal of liquid film dewetting on chemically patterned surfaces. A thin liquid film resting on a solid substrate that is heated or cooled from below experiences surface tension gradients, which lead to Marangoni flows. We explore the behavior of such a film on a chemically patterned substrate which drives film dewetting in order to determine how surface patterning and applied temperature gradients can be designed to influence the behavior of thin-film coatings. A nonlinear partial differential equation for the film height based on lubrication theory is solved numerically for a broad range of problem parameters. Uniform cooling of the substrate is found to significantly delay dewetting that is driven by wettability gradients. Uniform heating speeds up dewetting but can destroy the near-perfect templating imposed by the surface patterning. However, localized heating and cooling together can accelerate dewetting while maintaining templating quality. Localized heating and cooling can also be used to drive liquid onto areas that it would dewet from in the absence of heating. Overall, these results indicate that applied temperature gradients can significantly influence dewetting driven by surface patterning, and suggest strategies for the creation of spatially patterned thin-film coatings and flow control in microfluidic devices.
{ "pile_set_name": "PubMed Abstracts" }
Laparoscopic Nissen fundoplication: preliminary report. Twelve patients presenting with symptomatic esophagitis associated with hiatal hernia and gastroesophageal reflux underwent operative management under laparoscopic guidance. The antireflux procedure employed was the Nissen fundoplication. The authors completed the operation laparoscopically in nine patients. Postoperatively, patients were evaluated with repeat fiberoptic endoscopy, esophageal manometry, and barium contrast studies. Postoperative results were considered excellent on the basis of these studies and complete control of symptoms. The mortality rate was 0%. The only major operative complication was a pneumonia that occurred in one patient. At 1 month follow-up, six patients were totally asymptomatic. The authors conclude that laparoscopic treatment of gastroesophageal reflux associated with a hiatal hernia is feasible by a procedure that has already proven its value during open surgery.
{ "pile_set_name": "PubMed Abstracts" }
Effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects in Madrid (Spain). We aim to assess the effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects. To do so, we describe and compare the influenza vaccination coverage in the 2006/2007 campaign between the Autonomous Community of Madrid (ACM), where in year 2005 the recommendation was extended by 5 years to cover all those aged 60 and over, and other regions of Spain where the universally recommended age was 65 years and above. We used individualized secondary data provided by two surveys carried out in 2007 in ACM and in the rest of Spain. The total number of subjects included in the study was 21,948. For the 60-64 years age group influenza vaccination coverage was significantly higher 40.1% (CI 95% 36.4-43.8) in ACM residents than among residents in the Rest of Spain 29.1% (CI 95% 24.5-33.7). The difference in vaccine uptake was even greater, 59% (CI 95% 51.8-66.2) vs. 43.5%(CI 95% 34.3-52.7), when we compared subjects who suffered a chronic condition, which represents an indication for the anti-influenza vaccination. The results of the multivariate analysis show that the probability of a subject aged 60-64 living in ACM of being vaccinated was almost two times higher (OR 1.95 CI 95% 1.46-2.61) than a person of the same age who lived in a region of Spain where the universal recommendation for influenza vaccine started at 65 years. In conclusion, the available evidence indicates the effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects aged 60-64 years in our population.
{ "pile_set_name": "PubMed Abstracts" }
Construction of β to carbonyl stereogenic centres by asymmetric 1,4-addition of alkylzirconocenes to dienones and ynenones. Copper-catalyzed asymmetric 1,4-addition of alkylzirconium species to linear α,β,γ,δ unsaturated dienones and ynenones is reported. A variety of alkyl nucleophiles are introduced with good yields and excellent regio- and enantio-selectivities to give tertiary carbon centres bearing multiple functional groups. The method is also applicable to an ynethioate with ee's over 96%.
{ "pile_set_name": "PubMed Abstracts" }
Human exposures to bisphenol A: mismatches between data and assumptions. Human exposure to bisphenol A (BPA), a synthetic estrogen found in numerous consumer products, is widespread. However, scientific knowledge about the sources and routes of exposure remains incomplete. Although human biomonitoring studies report small amounts of bioactive BPA in the blood of most subjects, toxicokinetic models suggest that circulating levels should be undetectable. The conflict between reported data and toxicokinetic models has spurred considerable debate, with some suggesting that data from analyses of human blood should be dismissed in their entirety. This review addresses the assumptions used by previous risk assessment panels regarding the sources and routes of exposure to BPA (specifically, that BPA exposures occur solely via a few dietary sources) and how these assumptions have affected the interpretation of BPA studies. Given new experimental evidence that route of exposure influences BPA pharmacokinetics, we consider the implications of basing regulatory decisions on limited data that have provided incomplete information about the products that contain this chemical and how it enters the body. We also address evidence that challenges the assumption that humans metabolize BPA rapidly enough to result in undetectable levels in blood and therefore determine that there is a possibility of harm from current exposure levels. Our conclusions are consistent with the large number of hazards and adverse effects identified in laboratory animals exposed to low doses of BPA.
{ "pile_set_name": "PubMed Abstracts" }
Determination of critical eluent composition for polyethylenglycols using on-line liquid chromatography-Fourier transform infrared spectrometry. In this work, it has been extended to methanol:water mobile phases, the use of a background correction method for on-line LC-FTIR measurements named Univariate background correction based on the use of a reference spectra matrix (UBC-RSM) and absorbance ratios. It permits to overcome the problem related to spectral changes occurring during the gradient elution, which in the past limited the on-line coupling of LC and FTIR to isocratic elutions. The combined use of the aforementioned background correction technique in on-line isocratic and gradient LC-FTIR, and partial least squares (PLS) has been applied for the search of the critical conditions for polymers. Polyethylenglycol (PEG) has been used as a model example and results found fitted well with previously published ones.
{ "pile_set_name": "PubMed Abstracts" }
Resonance energy transfer between guanine nucleotide binding protein subunits and membrane lipids. Resonance energy transfer was used to estimate the distances of closest approach between fluorescent labels on G protein subunits (alpha, beta, and gamma) and the phospholipid bilayer surface. Fluorescein-labeled alpha, beta, and gamma subunits were the energy transfer donors and hexadecylaminoeosin (HAE) in phospholipid vesicles was the acceptor. Bovine brain G protein (alpha o, beta, and gamma subunits) were individually labeled with fluorescein as described in the accompanying paper [Kwon et al. (1993) Biochemistry (preceding paper in this issue)]. Fluorescein-labeled subunits were combined with the appropriate unlabeled G protein subunits and reconstituted into phospholipid vesicles. HAE quenched the fluorescein emission in a concentration-dependent manner which was dependent upon the G protein subunit labeled (gamma = beta > alpha o). From steady-state quenching data with hexadecylaminofluorescein (HAF) as a standard to determine the density of HAE in the phospholipid bilayer, the calculated distances between fluorescein-alpha o, -beta, and -gamma and HAE are 46 +/- 2, 38 +/- 3, and 37 +/- 2 A, respectively. Energy transfer was identified as the means of fluorescence quenching by two methods: (1) addition of 0.1% Lubrol reversed the quenching of fluorescein-labeled G protein subunits by HAE and (2) sensitized HAE emission was observed in the presence of fluorescein-labeled G protein subunits. These results are the first physical measurements of the distances between sites on G protein subunits and the lipid bilayer. These data demonstrate that the label in the beta and gamma subunits is closer to the lipid bilayer than that in the alpha subunit.
{ "pile_set_name": "PubMed Abstracts" }
Microbial community dynamics in a chemolithotrophic denitrification reactor inoculated with methanogenic granular sludge. Denitrification is applied in the tertiary treatment of wastewater to reduce nitrogen pollution. Fluorescence in situ hybridization (FISH), catalyzed reporter deposition (CARD)-FISH, cloning, and scanning electron microscopy (SEM) were applied to follow the evolution of the microbial composition and structure of granular sludge in chemolithotrophic denitrifying bioreactors fed with nitrate and thiosulfate. FISH oligonucleotide probes for the chemolitoautotrophic denitrifiers Thiobacillus denitrificans and Thiomicrospira denitrificans were designed and their utility tested. CARD-FISH and cloning data showed that bacterial diversity in the biofilms changed during the reactor operation. Chemoorganotrophic fermentative Gram-positive strains in the phyla, Actinobacteria and Firmicutes, were dominant in the methanogenic inoculum, both in terms of biodiversity and in number. Other significant phyla were Bacteroidetes and Chloroflexi. After 6 months of operation, Proteobacteria became dominant (83% of the clones). The diversity of Gram-positive bacteria was partially maintained although their abundance decreased notably. After 110 d of operation, the abundance of Tb. denitrificans cells increased considerably, from 1% to 35% of total DAPI-stained cells and from no isolated clones to 15% of the total clones. Tm. denitrificans only represented a minor fraction of the microorganisms in the sludge (1-4% of the DAPI-stained cells). These findings confirm that Tb. denitrificans was the dominant chemolitoautotrophic denitrifying microorganism in the bioreactors. The Archaeal diversity remained almost unchanged and it was represented mostly by Methanosaeta soehngenii. SEM results indicated a considerable loss in the integrity of the sludge granules during the operation, with risk of sludge buoyancy.
{ "pile_set_name": "PubMed Abstracts" }
From Phenanthrylene Butadiynylene Macrocycles to S-Heterocycloarenes. The first member of S-heterocycloarenes was synthesized from an easily prepared phenanthrylene ethynylene macrocycle through diyne cyclocondensation and a Scholl reaction. The solution-processed thin film of this S-heterocycloarene behaved as a p-type semiconductor.
{ "pile_set_name": "PubMed Abstracts" }
Bromocriptine therapy in patients with acromegaly: effects on growth hormone, somatomedin A and prolactin. Six of ten patients were subjectively improved by bromocriptine treatment as illustrated by diminished sweating, reduction of soft tissue swelling and restoration of sexual potency and menstruations. These six patients had elevated or normal blood levels of prolactin, which could be stimulated by TRH and inhibited by bromocriptine. During medication two clinical responders normalized and one lowered plasma GH concentrations. Three clinical responders with initially increase somatomedin A levels normalized these levels during treatment, in one case despite lack of effect on GH levels. The four nonresponders had undetectable or notably depressed levels of prolactin, which could not be stimulated by TRH. It is suggested that the presence of prolactin, per se or as an indication of a certain dopaminergic situation, is a prerequisite for successful bromocriptine treatment of patients with acromegaly.
{ "pile_set_name": "PubMed Abstracts" }
[Update on neuro-oncology]. This paper summarizes the recent advances in the field of neuro-oncology. Improvement in the surgical procedures and radiosurgery, correlation between genetic alteration and the chemosensitivity of some primary brain tumors, definition of optimal therapeutic regimen in primary central nervous system lymphoma and better insights in the physiopathology of paraneoplastic syndrome represent the most significant contribution in the field over the past three years.
{ "pile_set_name": "PubMed Abstracts" }
[Somatostatin receptors in immune system cells]. Many hormones and some neuropeptides and neurotransmitters play a key role in regulating numerous lymphoid cell functions. In particular, somatostatin (ss), substance P (sp) and vasoactive intestinal polypeptide (vip) appear to be involved in numerous regulating mechanisms of cell activities in the immune system under both physiological and pathological conditions. ss may be produced by lymphoid cells and accessories as part of the immune system. The distribution of somatostatin receptors (ssr) in the normal human thymus has prompted the hypothesis that ss, and probably other neuropeptides, may play an important role in cell homeostasis in this organ, as well as being one of the processes that regulates the maturation of T lymphocytes. The advent of molecular biology has showed a variable expression of ssr on the various T and B cell lines or lines deriving from lymphoma/ leukemia and human myeloma. Using autoradiographic studies, ssr have been predominantly found in lymphoblastic areas of lymphoma, which represent the active part of the tumour. The expression of ssR has been found in vivo and in vitro, also in pathological sites in patients with autoimmune and granulomatous diseases like rheumatoid arthritis and sarcoidosis.
{ "pile_set_name": "PubMed Abstracts" }
Tracheal intubation with the Macintosh laryngoscope versus intubating laryngeal mask airway in adults with normal airways. We tested the hypothesis that haemodynamic changes to intubation and postoperative pharyngolaryngeal morbidity are similar for blind intubating laryngeal mask (ILM)-guided compared with laryngoscope-guided tracheal intubation in adults with normal airways. We also compared intubation success rates and airway complications. One-hundred and fifty paralysed, anaesthetized adult patients undergoing elective surgery were randomly assigned to one of three equal-sized groups: 1. blind intubation via the ILM using a straight, silicone tube; 2. intubation with a Macintosh laryngoscope using a straight silicone tube and 3. intubation with a Macintosh laryngoscope using a polyvinyl chloride tube (controls). A standard sequence of adjusting manoeuvres was followed if intubation was difficult. The number of adjusting manoeuvres and intubation attempts, time to intubation, intubation success rate (first attempt and within 3 min), haemodynamic changes (pre-induction, post-induction, post-intubation), oesophageal intubation, mucosal trauma (blood detected), hypoxia (SpO2 < 95%) and postoperative pharyngolaryngeal morbidity (double-blinded) were documented. Time to successful intubation was longer (57 vs 35 s), and more intubation attempts were required in the ILM group (P < 0.0001). The intubation success rate was 100% (all first attempt) for the laryngoscope groups and 94% (56% first attempt) for the ILM group. There were no significant differences in heart rate or blood pressure among groups. Oesophageal intubation (26 v 0%) and mucosal trauma (19 v 2%) were more common in the ILM group. Hypoxia and postoperative pharyngolaryngeal morbidity were similar among groups. Blind intubation through the ILM offers no advantages over the Macintosh laryngoscope for adult patients requiring intubation for elective surgery with normal airways, but it is a feasible alternative.
{ "pile_set_name": "PubMed Abstracts" }
Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinoma. The usefulness of high-resolution sonography in diagnosing cervical lymph node metastases from papillary thyroid carcinoma was investigated. The accuracy of a particular sign, cystic change within a node, in establishing the diagnosis was assessed. The sonographic findings in 63 patients with enlarged cervical lymph nodes were retrospectively reviewed. The patients had undergone high-resolution gray-scale and color Doppler sonography followed by ultrasound-guided fine-needle aspiration (FNA) in all patients and surgical excision in 27 patients. Abnormal sonographic features were present in the lymph nodes of all 63 patients. In 14 (70%) of 20 patients with papillary thyroid carcinoma, sonography depicted cystic changes. This pattern was not found in any of the other 43 patients, in whom FNA revealed either metastasis from another malignancy (22 patients) or benign reactive lymphadenopathy (21 patients). Among the 63 patients, there were 43 true-negative, 14 true-positive, 6 false-negative, and no false-positive results in the diagnosis of metastatic papillary thyroid carcinoma using the presence or absence of an intranodal cystic area on sonography. These results yielded a 70% sensitivity, 100% specificity, 100% positive predictive value, 88% negative predictive value, and 90% overall accuracy for this criterion. Cystic changes within a cervical lymph node are highly suggestive of metastatic papillary thyroid carcinoma.
{ "pile_set_name": "PubMed Abstracts" }
Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma. Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.
{ "pile_set_name": "PubMed Abstracts" }
Pilot evaluation of an instrument to measure quality of life in British children with inflammatory bowel disease. The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.
{ "pile_set_name": "PubMed Abstracts" }
Improvement in activities of daily living in elderly following treatment for post-bereavement depression. To determine if elderly bereaved depressed subjects display difficulty with activities of daily living (ADL) and if their ADL difficulty improves with psychopharmacologic intervention. The Assessment of Motor and Process Skills (AMPS), an ADL assessment measuring ADL motor and ADL process skills, was administered to a pilot sample of elderly persons with post-bereavement depression prior to psychopharmacologic intervention and subsequently during treatment response. In the pretreatment phase, subjects displayed difficulty with ADL motor and ADL process skills that significantly improved during the treatment response phase. Results suggest that elderly bereaved depressed individuals demonstrated ADL difficulty that responds positively to psychopharmacologic intervention.
{ "pile_set_name": "PubMed Abstracts" }
Universality in quantum chaos and the one-parameter scaling theory. The one-parameter scaling theory is adapted to the context of quantum chaos. We define a generalized dimensionless conductance, g, semiclassically and then study Anderson localization corrections by renormalization group techniques. This analysis permits a characterization of the universality classes associated to a metal (g-->infinity), an insulator (g-->0), and the metal-insulator transition (g-->g(c)) in quantum chaos provided that the classical phase space is not mixed. According to our results the universality class related to the metallic limit includes all the systems in which the Bohigas-Giannoni-Schmit conjecture holds but automatically excludes those in which dynamical localization effects are important. The universality class related to the metal-insulator transition is characterized by classical superdiffusion or a fractal spectrum in low dimensions (d < or = 2). Several examples are discussed in detail.
{ "pile_set_name": "PubMed Abstracts" }
Heavy metal uptake by polyphosphate bodies in living and killed cells of Plectonema boryanum (cyanophycae). The study was conducted to determine whether living or killed cell polyphosphate bodies (PPB) would sequester more of several heavy metals. Living and heat- or glutaraldehyde-killed cells were exposed to 20 ppm of Zn, Pb, Mn and Al. Air-dried cells on Formvar-coated grids were first observed in the transmission electron microscope. The unit was then switched to the scanning transmission mode of operation with the spot setting. X-rays were collected on an energy dispersive X-ray spectrometer and mass fractions of the metals were determined. In all cases live cells sequestered a larger amount of the metal than cells killed by boiling or with glutaraldehyde. In all cases the cells killed by glutaraldehyde sequestered more of the heavy metals than cells killed by boiling. The results of the investigation show that PPB in living cells with active uptake systems take up and sequester more of the metals Zn, Pb, Mn and Al than killed cells.
{ "pile_set_name": "PubMed Abstracts" }
Steroid hormone influence on melanomagenesis. Disparities in the prognosis and incidence of melanoma between male and female patients have led clinicians to explore the influence of steroid hormones on the development and progression of this malignancy. A better understanding of the disparities of melanoma behavior between sexes and ages could lead to improved prevention and treatment options. There are multiple themes in the literature that unify the physiologic functions of estrogen and androgen receptors; herein we discuss and map their pathways. Overall, it is important to understand that the differences in melanoma behavior between the sexes are multifactorial and likely involve interactions between the immune system, endocrine system, and environment, namely UV-radiation. Melanoma deserves a spot among hormone-sensitive tumors, and if tamoxifen is re-introduced for future therapy, tissue ratios of estrogen receptors should be obtained beforehand to assess their therapeutic predictive value. Because androgens, estrogens, and their receptors are involved in signaling of commonly mutated melanoma pathways, potential synergistic properties of the recently developed molecular kinase inhibitors that target those pathways may exist.
{ "pile_set_name": "PubMed Abstracts" }
Understanding the art of feminist pedagogy: facilitating interpersonal skills learning for nurses. The purpose of this study is to explore feminist pedagogy integrated with facilitation skills. A pedagogy project was undertaken with students participating in the BSc (Hons) Nursing programme, whereby a module, "Interpersonal Skills for Nurses" was developed for 72 year 1 students. A feminist pedagogy involves employing the powers of diversity to create an environment where all students' voices are heard. It values the power of sharing to create a community of learners in which teachers and students share their talents, skills and abilities to enhance the learning of all (Chinn, 2001). An end of semester evaluation provided feedback which indicated this was a valuable module to teach year 1 student nurses. It highlighted that student nurses found the topic both interesting and relevant and felt it was taught in a way that promoted their personal development and identity as a nurse.
{ "pile_set_name": "PubMed Abstracts" }
Membrane protein oxidation determines neuronal degeneration. Oxidative stress is an early hallmark in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. However, the critical biochemical effector mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In screening various peroxides and potential substrates of oxidation for their effect on neuronal survival, we observed that intramembrane compounds were significantly more active than aqueous or amphiphilic compounds. To better understand this result, we synthesized a series of competitive and site-specific membrane protein oxidation inhibitors termed aminoacyllipids, whose structures were designed on the basis of amino acids frequently found at the protein-lipid interface of synaptic membrane proteins. Investigating the aminoacyllipids in primary neuronal culture, we found that the targeted protection of transmembrane tyrosine and tryptophan residues was sufficient to prevent neurotoxicity evoked by hydroperoxides, kainic acid, glutathione-depleting drugs, and certain amyloidogenic peptides, but ineffective against non-oxidative inducers of apoptosis such as sphingosine or Akt kinase inhibitors. Thus, the oxidative component of different neurotoxins appears to converge on neuronal membrane proteins, irrespective of the primary mechanism of cellular oxidant generation. Our results indicate the existence of a one-electron redox cycle based on membrane protein aromatic surface amino acids, whose disturbance or overload leads to excessive membrane protein oxidation and neuronal death. Membrane proteins have rarely been investigated as potential victims of oxidative stress in the context of neurodegeneration. This study provides evidence that excessive one-electron oxidation of membrane proteins from within the lipid bilayer, depicted in the graphic, is a functionally decisive step toward neuronal cell death in response to different toxins.
{ "pile_set_name": "PubMed Abstracts" }
[Peribuccal esthetic surgery]. This paper concerns the procedures of remodelling the peribuccal area for aesthetic purposes; these techniques may be planned in isolation or as a complement to a face-lift. In our hands these interventions are helpful firstly to correct and excessively deep nasolabial fold and sublabial crease using dermis or fascia grafts. Secondly, are designed to correct the contour of the upper lip either by smoothening the fine vertical folds, excising a fine strip of skin along the cupid's bow associated with dermabrasion or by diminishing the labial height resecting a buffalo-horn shaped cutaneous strip at the nasal vestibular sill and at the base of the columella. The philtrum is sculptured by dissecting the philtral columns. The medial philtral depression is maintained using translabial mattress sutures. Furthermore the upper and lower lips themselves are able to be augmented by means of dermal or fascia grafts or on the contrary thinned by resecting an appropriate horizontal strip of vermilion or mucous membrane, without any lesion of the orbicularis muscle. To eliminate the sadness of sagging buccal angles, we model the subcutaneous tissue of the labial commissure.
{ "pile_set_name": "PubMed Abstracts" }
Evaluation of rhizobacterial indicators of tobacco black root rot suppressiveness in farmers' fields. Very few soil quality indicators include disease-suppressiveness criteria. We assessed whether 64 16S rRNA microarray probes whose signals correlated with tobacco black root rot suppressiveness in greenhouse analysis could also discriminate suppressive from conducive soils under field conditions. Rhizobacterial communities of tobacco and wheat sampled in 2 years from four farmers' fields of contrasted suppressiveness status were compared. The 64 previously identified indicator probes correctly classified 72% of 29 field samples, with nine probes for Azospirillum, Gluconacetobacter, Sphingomonadaceae, Planctomycetes, Mycoplasma, Lactobacillus crispatus and Thermodesulforhabdus providing the best prediction. The whole probe set (1033 probes) revealed strong effects of plant, field location and year on rhizobacterial community composition, and a smaller (7% variance) but significant effect of soil suppressiveness status. Seventeen additional probes correlating with suppressiveness status in the field (noticeably for Agrobacterium, Methylobacterium, Ochrobactrum) were selected, and combined with the nine others, they improved correct sample classification from 72% to 79% (100% tobacco and 63% wheat samples). Pseudomonas probes were not informative in the field, even those targeting biocontrol pseudomonads producing 2,4-diacetylphloroglucinol, nor was quantitative polymerase chain reaction for 2,4-diacetylphloroglucinol-synthesis gene phlD. This study shows that a subset of 16S rRNA probes targeting diverse rhizobacteria can be useful as suppressiveness indicators under field conditions.
{ "pile_set_name": "PubMed Abstracts" }
Pinning down the role of common luminal intestinal parasitic protists in human health and disease - status and challenges. While some single-celled intestinal parasites are direct causes of diarrhoea and other types of intestinal pathology, the impact of other gut micro-eukaryotes on human health remains elusive. The fact that some common luminal intestinal parasitic protists (CLIPPs) have lately been found more often in healthy than in diseased individuals has fuelled the hypothesis that some parasites might in fact be protective against disease. To this end, the use of new DNA technologies has helped us investigate trans-kingdom relationships in the gut. However, research into these relationships is currently hampered by the limited data available on the genetic diversity within the CLIPPs genera, which results in limited efficacy of publicly available DNA sequence databases for taxonomic annotation of sequences belonging to the eukaryotic component of the gut microbiota. In this paper, I give a brief overview of the status on CLIPPs in human health and disease and challenges related to the mapping of intestinal eukaryotic diversity of the human gut.
{ "pile_set_name": "PubMed Abstracts" }
Microwave Parboiling: Reduction in Process Time, Browning of Rice and Residual Phosphorus Content in the Waste Water. The conventional prolonged parboiling process results in high operation cost and grain darkening, which may limit consumption. Moreover, residue generation by rice industries is another challenge. The objective of this study was to evaluate the use of microwave irradiation during soaking and gelatinization stages of parboiling rice. Processing time, colorimetric profile, broken and nongelatinized grains, sucrose and glucose content, free 5-hydroxymethyl-2-furfural, and residual phosphorus were evaluated. As the soaking and gelatinization times during microwave treatments increased, the colorimetric parameters increased; however, the values were lower than those with the conventional process. Regardless of soaking time, a decrease in broken and nongelatinized grains was obtained by using the lowest steaming time (5 min). Additionally, lower residual phosphorus content was found in soaking water (10 and 20 min) when using microwave irradiation. Under favorable conditions, a reduction in the levels of broken and nongelatinized grains, residual phosphorus, and color changes was observed, indicating that microwave irradiation may be more beneficial than conventional parboiling. PRACTICAL APPLICATION: Parboiling requires a high volume of water and soaking time, which leads to high costs, underutilization of infrastructures, and high residue in the water after processing. The rapid parboiling process involves the use of microwaves during the soaking and gelatinization stages. The main advantages of the microwave parboiling process include reduced processing time, ranging from 83% to 95%, higher gelatinization, greater yield, reduced darkening, and reduced residual phosphorus in the effluents by 60%. This report can aid industries in streamlining their processes, thereby providing a high-quality, lower cost, and environmentally safe product.
{ "pile_set_name": "PubMed Abstracts" }
Cellular events in the evolution of experimental diabetic nephropathy. In several models of progressive glomerular disease, mesangial cell proliferation, phenotypic change and increased growth factor expression precede up-regulation of genes for extracellular matrix components (ECM) and mesangial expansion. To examine these events in diabetic nephropathy (DN) we conducted sequential studies of glomeruli in rats with streptozotocin induced DN. We found prominent mesangial cell proliferation at three days (4.34 +/- 2.24 PCNA + cells/glom vs. 1.6 +/- 0.74 in controls, P < 0.001) associated with increased alpha-actin expression. PDGF B-chain mRNA was slightly increased at day one, and PDGF B-chain immunostaining was slightly increased at days one and six. Staining for bFGF was significantly increased at three days (2.2 +/- 0.6 vs. 1.2 +/- 0.1 in controls, P < 0.01). There was also an early increase in platelets in glomeruli of diabetic animals, and platelet depletion significantly inhibited the early phase of proliferation. In addition to mesangial cell proliferation, a prominent glomerular macrophage infiltration began at day three and peaked at day 30 (3.94 +/- 1.47 vs. 2.08 +/- 1.13 in controls, P < 0.01). TGF-beta mRNA increased at days 14 and 30. Insulin treatment prevented mesangial cell proliferation, actin expression, and macrophage infiltration, and normalized TGF-beta expression at 14 and 30 days. These multiple cellular events preceded any detectable increases in glomerular gene expression or deposition of collagen I, IV or laminin.
{ "pile_set_name": "PubMed Abstracts" }
Cytofluorometry as a method for the differentiation of trypanosomes. The DNA binding guanine specific antibiotic, chromomycin A3, has been evaluated for fluorescence intensity measurements of T. cruzi, T. brucei brucei and T. musculi. Optimal fixation and staining conditions have been determined. The fluorometry was performed with a microscope photometer equipped with electronic systems for short time excitation of 7 milliseconds and operation control. The trypomastigote bloodstream forms of these species have a different chromomycin specific DNA content. The total DNA content of T. cruzi was 2.1-fold higher than for T.b. brucei and 2.3-fold higher than for T. musculi. The nuclear DNA content also was higher in T. cruzi. The nuclear DNA values were recorded to be 1.6-fold greater than in T.b. brucei and 2.0-fold greater than in T. musculi. The amount of the kinetoplast DNA of T. cruzi was shown to be 3.2-fold higher than in T. musculi and 11.7-fold higher than in T.b. brucei. The higher total DNA of T.b. brucei in relation to T. musculi was based on the nuclear values because the content of the kinetoplast DNA of T.b. brucei was 3.7-fold smaller than of T. musculi. The kDNA comprised 25% in T. cruzi, 18% in T. musculi and only 4% in T.b. brucei of the total amount of the chromomycin specific DNA. The chromomycin fluorescence intensities of the DNA of trypanosomes were subjected to a statistical model of discriminant analysis. It was possible to get perfect separation of the three trypanosome species. The hit rate was 100%.
{ "pile_set_name": "PubMed Abstracts" }
Effect of intracellular glutathione on the production of prostaglandin D2 in RBL-2H3 cells oxidized by tert-butyl hydroperoxide. The liberation of arachidonic acid and the production of prostaglandin D2 (PGD2) were significantly influenced by peroxide and the level of intracellular glutathione (GSH). The productions of free arachidonic acid and PGD2 in RBL-2H3 cells were enhanced considerably by exposure to tert-butyl hydroperoxide (t-BHP). The liberation of arachidonic acid induced by t-BHP was not inhibited by EGTA. The productions of PGD2 and arachidonic acid induced by t-BHP were significantly facilitated by the depletion of intracellular GSH using buthionine sulfoximine (BSO) or diethyl maleate (DEM), although the depletion of GSH had no effect on the production of PGD2 induced by A23187. t-BHP failed to activate the conversion of free arachidonic acid to PGD2, since the formation of PGD2 from exogenously added arachidonic acid was not enhanced by treatment with t-BHP. The level of lipid hydroperoxides in t-BHP-treated cells was significantly elevated by treatment with DEM. These results suggest that hydroperoxides increase the free arachidonic acid available for the synthesis of PGD2 by activating phospholipase A2 (PLA2) and that the depletion of GSH by DEM accelerates the activation of PLA2 by raising peroxide levels in cells. Thus, the observed alterations in GSH levels are large enough to cause increased PGD2 synthesis in RBL-2H3 cells exposed to oxidative stress.
{ "pile_set_name": "PubMed Abstracts" }
Molecularly imprinted silica prepared with immiscible ionic liquid as solvent and porogen for selective recognition of testosterone. 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF(4)), an ionic liquid (IL) immiscible with water, was used as a new type of solvent and porogen for the preparation of molecularly imprinted silica. The new imprinted silica was prepared by a sacrificial spacer molecular imprinting approach with testosterone as template molecule. The new covalent monomer-template complex used in the imprinting procedure was synthesized via the reaction of 3-(triethoxysilyl)propyl isocyanate with testosterone. The imprinted silica was characterized by FT-IR spectroscopy, N(2) gas adsorption-desorption isotherm and the high-resolution transmission electron microscopy. Moreover, the selective adsorption ability of the imprinted particles towards testosterone was investigated by the steady-state binding experiment with testosterone propionate as its structural analogue. Results showed that the imprinted silica obtained in this study had relatively homogenous structure with numerous mesopores, indicating that the IL used here is an excellent solvent and satisfactory porogen for the preparation of imprinted materials. Moreover, ILs are more environmentally friendly than traditional organic solvents due to their negligible vapor pressure. The imprinted silica possesses highly specific recognition property and high binding capacity towards testosterone, showing that the new imprinting technique is relatively successful.
{ "pile_set_name": "PubMed Abstracts" }
[Application of a pH feedback-controlled substrate feeding method in glutamic acid fermentation]. A novel method based on pH value was proposed to simplify the substrate feeding method for glutamic acid fermentation. The linear relationship between the consumption amounts of ammonia (x) and that of glucose (y) was established (y = 7.4744x, R2 = 0.9989) which could be used as the ratio of the amount of ammonia and that of glucose in the feeding broth. Thus the concentration of glucose could be controlled through the adjustment of pH automatically. In the glutamic acid fermentation using the pH feedback-controlled glucose feeding method, the glucose concentration in fermentation broth was maintained between 12 and 21 g/L. Compare with the constant glucose concentration feeding method, the glucose conversion rate and glutamic acid productivity increased by 9.06% and 17.5% respectively, when the pH feedback-controlled glucose feeding method was employed, and fermentation period was shorten above 2 h.
{ "pile_set_name": "PubMed Abstracts" }
Competence and Satisfaction in Occupational Performance Among a Sample of University Students: An Exploratory Study. Success at university may be influenced by concerns with occupation and occupational performance. To understand occupations of concern and occupational performance among a sample (N = 144) of university students in the Midwest United States, the Canadian Occupational Performance Measure was administered. Socially related (n = 103), academic-related (n = 75), and work-related (n = 64) occupations were the three most frequently reported occupational concerns. Time management (n = 79) was the most frequent person-level concern. Mean self-perceived competence in occupations was 29.83 (SD = 7.18) out of 50 and mean performance satisfaction was 26.80 (SD = 8.01) out of 50. There were no differences in occupational performance across gender, race/ethnicity, class standing, living environment, or work status. However, within participants, there was a significant and clinically relevant difference between performance satisfaction and self-perceived competence in occupation, t(143) = 7.052, p < .0005, d = 0.58. Students have varied occupations that they find important, and future research should explore how occupational performance and performance satisfaction influence university success.
{ "pile_set_name": "PubMed Abstracts" }
L-Carnitine inhibits eryptosis induced by uremic serum and the related mechanisms. To investigate whether L-carnitine (LC) inhibits eryptosis induced by uremic serum and the related mechanism. One percent erythrocyte suspension was cultured by three kinds of mediums in vitro, which was included in the control group (Group C, phosphate buffered saline [PBS]), the uremic serum group (Group U, 30% uremic serum + 70% PBS) and the LC group (Group L, 30% uremic serum + 70% PBS + 200 umol/L LC), respectively. Erythrocytes were collected at 24 and 48 h, respectively. Phosphatidylserine (PS) was estimated from Annexin-V-binding and reactive oxygen species (ROS) by flow cytometry, glutathione (GSH) was estimated from Enzyme linked immunosorbent assays (ELISA) by Microplate reader. Eryptosis in Group C increased as the incubating time extended (3.43 ± 0.37 at 24 h, 4.21 ± 0.44 at 48 h). Eryptosis increased in Group U compared with Group C (6.5 1 ± 0.71 at 24 h, p < 0.01; 8.55 ± 0.76 at 48 h, p < 0.01), while decreased in Group L compared with Group U (5.80 ± 0.69 at 24 h, p < 0.05; 7.87 ± 0.76 at 48 h, p < 0.05). Meanwhile, ROS of erythrocytes increased in Group U compared with Group C (33.12 ± 1.61 versus 14.83 ± 2.22 at 24 h, p < 0.01; 42.06 ± 1.81 versus 20.94 ± 1.78 at 48 h, p < 0.01), and GSH decreased in Group U compared with Group C (25.66 ± 0.32 versus 31.27 ± 0.38 at 24 h, p < 0.01; 8.53 ± 0.59 versus 17.29 ± 0.54 at 48 h, p < 0.01). ROS of erythrocytes decreased in Group L compared with Group C (26.29 ± 1.69 at 24 h, p < 0.01; 36.21 ± 2.00 at 48 h, p < 0.01). GSH increased in Group L compared with Group U (27.54 ± 0.60 at 24 h, p < 0.01; 15.18 ± 0.42 at 48 h, p < 0.01). LC inhibits eryptosis induced by uremic serum, which possibly relates to oxidative stress in part.
{ "pile_set_name": "PubMed Abstracts" }
A cysteine protease from Taenia solium metacestodes induce apoptosis in human CD4+ T-cells. Here we investigated whether the depletion of CD4+ lymphocytes, observed in mononuclear cells incubated with Taenia solium metacestode E/S products or with living cysts was due to apoptosis. Using the deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL), electron microscopy and DNA gel electrophoresis, we found signs of apoptosis in these cells. Results showed that cysteine protease activity was responsible for this effect, since E-64 prevented cell death in all cases. Electron microscopy studies showed that lymphocytes exhibited features of apoptosis such as cellular membrane integrity, strangling and fragmentation of nuclei, chromatin condensation, apoptotic bodies and loss of microvilli. In contrast, lymphocytes co-cultured with living metacestodes plus E-64 exhibited integrity of their structures. DNA fragmentation was detected by TUNEL assays and DNA gel electrophoresis. The results suggested that cell death induced by the cysteine protease from the T. solium metacestode may be involved in down-regulation of cell-mediated responses in infected hosts.
{ "pile_set_name": "PubMed Abstracts" }
Yawning. YAWNING IS A COMMON PHYSIOLOGICAL EVENT THAT CAN BE DIVIDED INTO THREE DISTINCT PHASES: a long inspiratory phase, a brief acme and a rapid expiration. The aim of yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning probably has an important role for social communication as well. Yawning can be responsible for pain, luxation or even transient ischaemic attack. Abnormal yawning is present in various pathologies: migraine, Parkinson's disease, tumours, psychiatric diseases, infections or iatrogenic pathologies. The neuro-pharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus. Oxytocin may then activate cholinergic transmission in the hippocampus and, finally, acetylcholine might induce yawning via the muscarinic receptors of the effectors. This is an over-simplification; many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides. Dopamine involvement in yawning could have practical applications in the study of new drugs or the exploration of neurological diseases such as migraine or psychosis. 2001 Harcourt Publishers Ltd
{ "pile_set_name": "PubMed Abstracts" }
Microtubule targeting agents: from biophysics to proteomics. This review explores various aspects of the interaction between microtubule targeting agents and tubulin, including binding site, affinity, and drug resistance. Starting with the basics of tubulin polymerization and microtubule targeting agent binding, we then highlight how the three-dimensional structures of drug-tubulin complexes obtained on stabilized tubulin are seeded by precise biological and biophysical data. New avenues opened by thermodynamics analysis, high throughput screening, and proteomics for the molecular pharmacology of these drugs are presented. The amount of data generated by biophysical, proteomic and cellular techniques shed more light onto the microtubule-tubulin equilibrium and tubulin-drug interaction. Combining these approaches provides new insight into the mechanism of action of known microtubule interacting agents and rapid in-depth characterization of next generation molecules targeting the interaction between microtubules and associated modulators of their dynamics. This will facilitate the design of improved and/or alternative chemotherapies targeting the microtubule cytoskeleton.
{ "pile_set_name": "PubMed Abstracts" }
Eight-membered-ring solid-state conformational interconversion via the atom-flip mechanism, a CPMAS 13C NMR and crystallographic stereochemical study. Nefopam methohalide (chloride, bromide, and iodide) medium-ring quaternary ammonium salts of the non-narcotic analgesic tertiary amine drug give crystals belonging to the identical monoclinic P2(1)/c space group, and all of these pseudopolymorphs exhibit the same packing motif. A singular boat-boat (BB) more compact conformation is observed in the nefopam methochloride crystal. Larger halide anions (bromide and iodide) increase the void distance between the 2(1)-screw axis related adjacent ammonium cations to accommodate void-size dependent equilibrium quantities of the twist-chair-chair (TCC) more extended conformation. The BB:TCC occupancy factors are 0.961(5):0.039(5) [193 K], 0.780(5):0.220(5) [293 K], and 0.755(6):0.245(6) [343 K] for the methobromide crystal, while values of 0.657(5):0.343(5) [193 K] and 0.592(7):0.408(7) [293 K] were measured for the methiodide. Above a minimum of ca. 2.53 A, the occupancy factors were found to be linearly correlated to the intermolecular (TCC)Me(eq)-H...H-Me(ax)(TCC) distance between abutting methyl group protons in 2(1)-screw axis related neighbors. Temperature-dependent occupancy factors for the two conformers are interpreted in terms of a medium ring atom-flip facile interconversion between the two low energy conformations in crystals containing the appropriate size intercation void. A BB/TCC atom-flip interconversion in the methochloride unit cell would result in van der Waals interactions due to an estimated 2.31 A close intermolecular (TCC)Me(eq)-H...H-Me(ax)(TCC) distance between adjacent 2(1)-screw symmetry ammonium cations. The 203 K low-temperature CPMAS 13C NMR spectrum of the methiodide salt showed two slow exchange limit (SEL) delta 57.91 [BB] and delta 63.10 [TCC] OCH2CH2N peaks. A variable low-temperature CPMAS NMR investigation of the solid methiodide showed complex dynamic behavior that cannot be interpreted solely on the basis of an atom-flip conformational interconversion. Local magnetic fields from the gem-dimethyl rapidly rotating proton magnetic dipoles provide a distance-dependent T1 relaxation mechanism for neighboring carbons in the solid-state.
{ "pile_set_name": "PubMed Abstracts" }
Access to self-management education, conservative treatment and surgery for arthritis according to socioeconomic status. There is now a considerable body of research investigating inequities in access to health care for arthritis according to socioeconomic status (SES). Conducted in a range of settings internationally, studies have examined specific socioeconomic factors (including education, income, deprivation and health insurance status) in relation to access to treatment. This chapter provides a comprehensive review of the available evidence on disparities in access to self-management education, conservative therapy and surgical treatment for arthritis, according to SES. There is some evidence of SES disparities in access to self-management education and advice, primary care, specialist care, physical therapy and medications, and strong evidence that people with less education or lower income experience significant disparities in access to joint replacement surgery. In view of research indicating that disparities may adversely affect patient outcomes, examples of initiatives designed to optimise access to care for disadvantaged groups are also described.
{ "pile_set_name": "PubMed Abstracts" }
The effect of isolated soy protein adjunctive with flaxseed oil on markers of inflammation, oxidative stress, acute phase proteins, and wound healing of burn patients; a randomized clinical trial. The objective was to determine the effect of isolated soy protein (ISP) and flaxseed oil (FO) on inflammatory and oxidative stress indices, acute phase proteins, and wound healing of burn patients. One hundred eighty-eight patients were assessed for eligibility in this randomized controlled trial. Of these, seventy-three eligible patients (total burn surface area 20-50%) were randomly assigned to 3 isocaloric groups, labeled as control (wheat flour+corn oil (CO)), ISP+FO, and ISP+CO, to receive these nutrients for 3 weeks. We used intention to treat analysis to overcome bias. Because of the large perturbation in water compartments, patients received nutrients from 4th to 25th day of admission. Serum high sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), superoxide dismutase (SOD), ferritin, albumin, and transferrin were measured. The wound area was evaluated by stereological test. During the 3-week intervention, hs-CRP (-19.4±5.6, -11.7±4.7μg/ml) and ferritin (-83.8±20.5, -80.1±19.6ng/ml) levels changes significantly reduced compared to the control group (P<0.05). MDA level (-0.05±0.21μmol/l) significantly decreased in group A (P<0/05) but was not significant in groups B and control (P>0.05). Albumin level (0.59±0.14, 0.30±0.12g/dl) significantly increased in group A compared to the control group (P<0.05), but no significant relationship was found between other groups (P>0.05). Transferrin level (4.9±3.6, 2.9±5.1g/dl) significantly increased in ISP groups compared to the control (P<0.05). SOD improved in all groups with no significant difference between them (P>0.05). The stereology examination showed significant improvement in wound healing in the ISP groups on days 22 and 25 compared to the control group. Nutritional supplements with ISP may attenuate post-burn oxidative stress and inflammation, leading to improved wound healing in burn patients. Flaxseed oil may not exert a beneficial effect over the ISP.
{ "pile_set_name": "PubMed Abstracts" }
Application of electrical impedance analysis for diagnosis of a pulmonary mass. The electrical impedance of a pulmonary mass was measured in 53 patients of whom 44 had primary lung cancer, 5 had metastatic lung tumor, and 4 had organizing pneumonia. Because biologic tissue can be regarded, electrically, to consist of extracellular resistance (Re), intracellular resistance (Ri), and the electrical capacitance of the cell membrane (Cm), these three parameters were calculated from the measured electrical impedance of tissue by a curve-fitting technique using a computer program. The Re of lung tissue was significantly greater (p < 0.01) and the Cm of lung tissue was significantly less (p < 0.01) than that of a pulmonary mass. The Re of malignant tumors (both lung cancer and metastatic tumors) was significantly greater (p < 0.01) and the Cm of malignant tumors was significantly less (p < 0.01) than that of organizing pneumonia. With this information, we used a biopsy needle to diagnose nine intrathoracic lesions. This technique additionally allowed us to confirm the proximity of the needle tip of the mass. The electrical impedance of the lung mass was measured through the biopsy needle using a modified impedance analysis system before the biopsy was performed. There were no false-negative results, and one false-positive result. The rapid measurement of the electrical impedance of a pulmonary mass, preoperatively, may be of value in the clinical evaluation of a pulmonary mass both by facilitating needle guidance and by permitting diagnosis based on electrical impedance.
{ "pile_set_name": "PubMed Abstracts" }
Successive episodes of synapses production in the developing rat nucleus tractus solitarii. In the rat nucleus tractus solitarii (NTS), synaptogenesis is thought to occur both pre- and postnatally. The present study was performed to precisely define the timetable of synapse formation in the NTS after birth. Changes in synapse morphology and densities were analyzed between postnatal day 3 (P3) and P28 using electron microscopy and ethanol phosphotungstic acid (E-PTA) staining. The proportion of morphologically immature synapses was high at P3 (38%) and P14 (30%) and low (8-14%) at the other ages investigated (P7, P21, and P28). Synaptic density significantly increased between P7 and P14 (60%) and between P21 and P28 (54%), but did not significantly change between P3 and P7 and between P14 and P21. Mean synaptic diameter also increased over the first postnatal month. Significant increases in synaptic size occurred between P3 and P7 (28%) and between P14 and P21 (15%). The present data indicate that, in the NTS, synaptogenesis occurs over a protracted period of time and involves distinct successive episodes of synapse production.
{ "pile_set_name": "PubMed Abstracts" }
[Electrophysiologic study, diagnosis and cases of acquired sensory polyneuropathy]. Sensory neuropathies encompass a group of neuropathies affecting solely or predominantly peripheral sensory nerves. They are rarely encountered in clinical practice. The authors review sensory nerve conduction studies and compare the various recording technics. Values of compound sensory action potential amplitude and sensory nerve conduction velocity are analyzed. On the basis of clinical and electrophysiological sensory impairment, three types of neuropathies can be proposed: neuropathies with either large, small or total myelinated fibers involvement. Lastly definable causes of sensory neuropathies are reviewed.
{ "pile_set_name": "PubMed Abstracts" }
Characterization of a new methylated beta-cyclodextrin with a low degree of substitution by matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography using evaporative light scattering detection. A new methylated beta-cyclodextrin with a low degree of substitution was characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high-performance liquid chromatography (HPLC) with evaporative light scattering detection. Using alpha-cyano-4-hydroxycinnamic acid as the matrix and the thin layer method as the deposition procedure, MALDI-TOF-MS revealed that the mixture was composed of CDs bearing from 2 to 8 methyl groups with an average degree of substitution (DS) of 0.7 (i.e. 0.7 methyl groups per glucopyranose unit). Using a Purospher Star RP-18 endcapped column with acetonitrile-water mobile phase in gradient elution mode, HPLC was employed at analytical scale to obtain a chromatographic fingerprint of the crude mixture and at semi-preparative scale to fractionate it. MALDI-TOF-MS of these fractions revealed that the overall retention of the different derivatives, which depicts their polarity, was mainly driven by the DS and increased with the number of methyl groups on the CD moiety.
{ "pile_set_name": "PubMed Abstracts" }
[Alterations in erythrocyte membrane. Effect of neutrophil activation]. White blood cells, especially polymorphonuclear neutrophils (PMN), are known to alter some hemorheological parameters. Most of in vitro results have been obtained with passive PMN. Stimulated PMN also lead to other hemorheological changes. In our study, we have firstly activated PMN with opsonized zymosan and collected a PMN-free supernatant after 30 minutes activation. This supernatant was secondarily incubated with erythrocytes either in whole blood or in suspension. After 10 minutes incubation, hemorheological parameters were evaluated: 1) red blood deformability (RBC) (Ektacytometer* Technicon), 2) RBC filtration (Hemorheometer MK 1), 3) RBC aggregation (Erythroaggregometer* Sefam), 4) Plasmatic and whole blood viscosities (Low Shear 30* Contraves). Our results show that activated PMN-supernatant increases rigidity index (IR) of RBC in suspensions (IR of RBC control = 14.59 +/- 3.30 towards RI of incubated RBC = 22.91 +/- 7.06 p less than 0.001). Other rheological parameters remain unchanged. Activated PMN suspenatant influence on RBC is slight but could suggest of an alteration of RBC membrane. With an in vitro model of washed platelets aggregation, we have previously demonstrated that proaggregant activity of PMN supernatant was inhibited by specific Platelet-Activating Factor (PAF-acether) antagonists: BN 52021, BN 50723, Web 2086. We have so compared both effects of activated PMN-supernatant and synthetic PAF-acether on RBC membrane fluidity. Membrane fluidity was studied by fluorescence polarization of 4 probes embedded at different deep in the membrane of intact RBC. Similar modifications of RBC membrane fluidity are observed with either synthetic PAF-acether or PMN supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
Conformational mapping of amyloid peptides from the putative neurotoxic 25-35 region. The secondary structure of amyloid beta A(25-35) and its deletion analogues was studied by circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy and molecular dynamics calculation. Data of our comparative CD and FTIR measurements in trifluoroethanol suggest that beta A(25-35)NH2 has a preferred beta-sheet conformation. Contrary to this beta A(31-35)NH2 tends to adopt a beta-turn conformation. Based on the comparable neurotoxic effect of beta A(25-35)NH2 and beta A(31-35)NH2 the neurotoxicity likely involves the same 31-35 core sequence and the "biologically active conformation" is a beta-turn rather than a beta-sheet structure.
{ "pile_set_name": "PubMed Abstracts" }
Prevalence of echocardiographic left-atrial enlargement in hypertension: a systematic review of recent clinical studies. Left atrial enlargement (LAE) is a marker of hypertensive heart disease associated with increased cardiovascular risk. We reviewed recent literature about the prevalence of LAE, as assessed by echocardiography, to update our information about the clinical relevance of this cardiac phenotype in human hypertension. We performed a search of MEDLINE using the key words "left atrial enlargement," "left atrial dilatation," "left atrial size," "hypertension," "echocardiography," and "atrial fibrillation" to identify relevant papers. We considered full articles published in English from January 1, 2000 to July 1, 2012 reporting studies involving adult individuals. We analyzed a total of 15 studies, including 10,141 untreated and treated subjects. LAE was defined according to 11 different criteria (4 studies applied two or three criteria), and its prevalence consistently varied among studies, from 16.0-83.0%, with a prevalence in the pooled population of 32%. A gender-based analysis of 9 studies (8,588 patients) showed the prevalence of LAE as being similar in women and men (OR, 1.23; 95% CI, 0.83-1.83; P = 0.30). Data provided by 10 studies (n = 9,354 patients) showed the prevalence of left-ventricular hypertrophy as being significantly higher in patients with LAE (68.2%) than in their counterparts without LAE (41.8%) (OR, 2.97; 95% CI, 2.68-3.29; P < 0.01). Our analysis shows that LAE is present in a relevant fraction of the hypertensive population. Because LAE is an independent predictor of cardiovascular events, the accurate detection of this phenotype may improve the evaluation of risk in hypertensive patients.
{ "pile_set_name": "PubMed Abstracts" }
Systematic identification of suspected anthelmintic benzimidazole metabolites using LC-MS/MS. Metabolite reference standards are often not available, which results in a lack of MS/MS spectra for library matching. Consequently, the identification of suspected metabolites proves to be challenging. The present study aims at structurally elucidating the MS/MS fragmentation behavior of selected benzimidazole anthelmintics to theoretically predict characteristic product ions for rapid and systematic tentative metabolite identification. A set of common characteristic product ions was identified from accurate mass MS/MS experiments for five parent compounds. It was hypothesized that the mass shift of any metabolic transformation at the parent molecule also is observable in the mass spectrum of the corresponding metabolite. This was tested and verified with six metabolite reference standards and subsequently, formulated as a general prediction scheme. The approach was integrated into a rapid MSe QTOF workflow and tested in mouse plasma for mebendazole and its metabolites. The presented scheme allows the prediction of characteristic product ions for suspected unknown metabolites. These can be matched with measured product ions of suspected metabolites for tentative identification. The theoretically predicted spectra can contribute to the tentative identification of unknown compounds in non-target and suspect screening approaches.
{ "pile_set_name": "PubMed Abstracts" }
The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia. Based on the fact that human bile and, particularly gallbladder bile, contains high physiological levels of the antioxidant melatonin, the aim of this study was to investigate whether the melatonin receptor MT1 is present in human gallbladder. Expression and localization of MT1 was assessed by RT-PCR, Western blotting and immunofluorescence analysis in gallbladder samples from patients with cholelithiasis and with advanced gallbladder carcinoma. Additionally, we monitored mRNA expression of the two key enzymes of melatonin synthesis, i.e. arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT). MT1 mRNA and protein were present in all cholelithiasis (n = 10) and gallbladder carcinoma (n = 5) samples. As indicated from RT-PCR and Western blot studies, MT1 is located in gallbladder epithelia. Epithelial expression was further proven by immunofluorescence staining of MT1 in paraffin-embedded cholelithiasis and gallbladder carcinoma sections. Analysis of AANAT and HIOMT mRNA expression showed that HIOMT mRNA is present in gallbladder. Surprisingly, AANAT was not detectable under conditions where it was found in a human colon specimen. The absence of AANAT suggests that in human gallbladder, HIOMT might be involved in the formation of 5-hydroxytryptamine products other than melatonin. In summary, our results provide the first evidence for the presence of MT1 in human gallbladder epithelia. Therefore, in addition to its profound antioxidative effects in the biliary system, melatonin might also act through MT1-mediated signal transduction pathways. Thereby, it might be involved in the regulation of gallbladder function.
{ "pile_set_name": "PubMed Abstracts" }
Resistance of Glycine tomentella to soybean leaf rust Phakopsora pachyrhizi in relation to ploidy level and geographic distribution. Accessions of five diploid and five tetraploid isozymically defined groups of Glycine tomentella collected from throughout the species range in Australasia were scored for resistance to three separate isolates of Phakopsora pachyrhizi, the causal agent of soybean leaf rust. Resistance levels were found to be high (>75%) in most of the groups. While resistance levels differed among groups, the overall levels in polyploids were similar to those in diploids. Geographical patterns of resistance and susceptibility to P. pachyrhizi indicate that two regions of susceptibility exist. The highest proportion of susceptible accessions occurs in the Kimberley Plateau region of Western Australia and the Northern Territory, while another region of susceptibility is found in the Townsville/Cairns region of Queensland. Results from genetic crosses between accessions within two forms of the tetraploids indicate that in the aneuploid form (2n = 78), resistance to P. pachyrhizi was under the control of a single dominant gene, whereas in a second group of tetraploids (2n=80), resistance was controlled by two or three gene loci.
{ "pile_set_name": "PubMed Abstracts" }
[Central pontine myelinolysis and hyponatremia]. Central pontine myelinolysis is a rare, but probably underreported, complication of the treatment of severe hyponatraemia. The typical presentation, with pseudobulbar palsy, quadriplegia and locked-in syndrome, made the diagnosis clinically possible in the two new cases reported. It was confirmed by computed tomography (CT). Serial CT scans in one case showed the chronological dissociation, as there was complete resolution of the pontine lucency several months after complete clinical recovery. Osmotic demyelination is suspected, but it remains unproven. Although recent evidence has suggested that too rapid a correction of severe hyponatraemia may be a possible factor, the two cases described occurred after slow correction. It would seem that rapid correction to a level of mild hyponatraemia (128-132 mmol.l-1) may be safe, reducing the morbidity of severe hyponatraemia without having central pontine myelinolysis.
{ "pile_set_name": "PubMed Abstracts" }
Current status of antioxidant therapy for Alzheimer's Disease. Accumulating evidence from preclinical and clinical studies supports the hypothesis that oxidative stress may be associated with the onset and progression of Alzheimer's Disease (AD). Antioxidant therapies are being promoted in the lay press to enhance mental functions and delay cognitive losses with aging. An increasing number of physicians are also recommending antioxidant therapies, such as high dose vitamin E, for subjects with AD and other neurodegenerative disorders. High dose vitamin E, ginkgo biloba, and selegiline are three putative antioxidants that have been tested in randomized multicenter trial conditions in the US. This paper summarizes the oxidative stress hypothesis of AD and reviews the strengths and limitations of published antioxidant studies in AD in relation to the role of such therapies in practice.
{ "pile_set_name": "PubMed Abstracts" }
Spontaneous imbibition of surfactant solution into an oil-wet capillary: wettability restoration by surfactant-contaminant complexation. For a given type of rock, the effectiveness of oil recovery through wettability alteration is highly dependent upon the nature of the water-soluble surfactant used. Different mechanisms have been proposed by others to explain wettability alteration by surfactants, and understanding the process is crucial to improve recovery performance. Known mechanisms include (1) surfactant adsorption onto the oil-wet solid surface (coating mechanism) and (2) surfactant molecules complexing with contaminant molecules from the crude oil which are adsorbed on the rock surface so as to strip them off (cleaning mechanism). With the second mechanism, the wettability is restored by lifting the contaminant layer away, exposing the rock surface which was originally water-wet. We previously focused on the numerical modeling of the surfactant coating mechanism (Hammond and Unsal Langmuir2009, 25, 12591; 2010, 26, 6206), and we now present a numerical study for the cleaning process. Our new model shows that when a wettability altering surfactant solution is allowed to imbibe spontaneously and acts by the cleaning process, the meniscus advances more rapidly than when there was wettability alteration by coating alone. In our previous model there was a concentration threshold below which imbibition was not possible. That threshold arose because a finite amount of surfactant needs to be adsorbed onto the oil-wet surface to change the contact angle to a water-wet value, but the maximum amount that can be absorbed is limited by the requirement that it be in equilibrium with the surfactant concentration near the meniscus. In the new model, with the cleaning mechanism there is no such threshold, since the cleaning process is driven by the surfactant flux into the vicinity of the advancing meniscus rather than the surfactant concentration there. As long as there are surfactant molecules present in the aqueous solution, the flux is nonzero and molecule pairs can form and alter the wettability by removing the contaminant from the oil-wet surface. However, under very low surfactant concentrations, the process is extremely slow compared to at higher concentrations.
{ "pile_set_name": "PubMed Abstracts" }
A novel photoelectrochemical biosensor for protein kinase activity assay based on phosphorylated graphite-like carbon nitride. Protein kinases are general and significant regulators in the cell signaling pathway, and it is still greatly desired to achieve simple and quick kinase detection. Herein, we develop a simple and sensitive photoelectrochemical strategy for the detection of protein kinase activity based on the bond between phosphorylated peptide and phosphorylated graphite-like carbon nitride (P-g-C3N4) conjugates triggered by Zr(4+) ion coordination. Under optimal conditions, the increased photocurrent is proportional to the protein kinase A (PKA) concentration ranging from 0.05 to 50 U/mL with a detection limit of 0.077 U/mL. Moreover, this photoelectrochemical assay can be also applied to quantitative analysis of kinase inhibition. The results indicated that the IC50 value (inhibitor concentration producing 50% inhibitor) for ellagic acid was 9.1 μM. Moreover, the developed method is further applied to detect PKA activity in real samples, which contains serum from healthy person and gastric cancer patients and breast tissue from healthy person and breast cancer patients. Therefore, the established protocol provides a new and simple tool for assay of kinase activity and its inhibitors with low cost and high sensitivity.
{ "pile_set_name": "PubMed Abstracts" }
[Proliferation and differentiation of hematopoietic stem cells in hypokinesia]. Using the method of exogenous cloning in vivo of the hemopoietic stem cells of the bone marrow and spleen in the femur and the spleen of mice it was shown that during hypokinesia the kinetics of the stem cells differed in both organs (the spleen and the bone marrow). Differentiation of transplanted stem cells from different sources was unchanged in the spleen, but stem cells of the bone marrow seeding in the femur changed the character of their differentiation in the direction of increase of the erythopoietic function, whereas stem cells of the spleen failed to alter the direction of differentiation.
{ "pile_set_name": "PubMed Abstracts" }
Endotoxin stimulates interleukin-6 production by human Kupffer cells. Interleukin-6 (IL-6) induces acute-phase protein synthesis in human hepatocytes. We evaluated whether the contiguous hepatic macrophages, human Kupffer cells (HKC), produce IL-6 in response to an inflammatory stimulus. HKC were harvested from collagenase-digested normal liver biopsies and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture, 5 x 10(5) HKC were repleted with fresh media with or without 2.5 micrograms/ml of endotoxin (LPS). Parallel cultures contained polymyxin-B (10 micrograms/ml) or antihuman-IL-6 antibody (4 units/ml). Timed supernatants were collected and IL-6 levels (ng/ml) measured (B9.9 proliferative bioassay). Data analysis was by the paired Student's t test. Unstimulated HKC produced negligible IL-6 levels (less than 0.150 ng/ml). Endotoxin invoked early and sustained HKC production of IL-6, which was completely (P less than 0.001) abrogated by the addition of the anti-IL-6 antibody. Polymyxin B, an LPS-inhibitor, also blocked (P less than 0.001) IL-6 production, indicating the specificity of the response to the inflammatory stimulus. This is the first evidence that HKC can produce IL-6 in response to LPS. Local intrahepatic production of IL-6 may provide a necessary paracrine signal for HKC to amplify directly neighboring hepatocyte acute-phase responses during inflammation in man.
{ "pile_set_name": "PubMed Abstracts" }
Dyslipidaemic pancreatitis clinical assessment and analysis of disease severity and outcomes. The relationship between pancreatitis and dyslipidaemia is unclear. Admissions with acute pancreatitis were prospectively evaluated. A comparison of the demographic profile, aetiology, disease severity scores, complications and deaths was made in relationship to the lipid profiles. From June 2001 to May 2005, there were 230 admissions. The pancreatitis was associated with alcohol (63%), gallstones (18%), idiopathic (9%) and isolated dyslipidaemia (10%). Dyslipidaemia was significantly different between the two predominant race groups: Indian 50.5% and African 17.9% (p < 0.000017). Seventy-eight (34%) had associated dyslipidaemia and 152 (66%) were normolipaemic at admission. The average body mass index was higher in the dyslipidaemic group (27 +/- 6) than in the normolipaemic group (24.5 +/- 6.20; p = 0.004). The mortality rate was similar between the dyslipidaemic and normolipaemic patients (10 and 8%, respectively) and unrelated to race (p = 0.58). The 9 deaths in the dyslipidaemic group occurred in those with persistent hypertriglyceridaemia irrespective of its level (p = 0.003). Dyslipidaemic pancreatitis was more common in the Indian ethnic group. Adverse outcomes in those with dyslipidaemia were predominantly associated with hypertriglyceridaemia.
{ "pile_set_name": "PubMed Abstracts" }
Adaptive changes of rat liver cells induced by repeated intraperitoneal injections of d-galactosamine. III-Light- and electron-microscopic investigations of hepatocellular cytoplasmic changes. In rats hepatocellular cytoplasmic changes after daily repeated D-galactosamine (GalN) intoxication--i.e. subacute GalN intoxication--were studied by light and electron microscopy. The number of GalN injections--and thus the days of survival--was between one and 30. The rats were killed six hours after the last GalN injection. Less degenerative changes were found after repeated GalN injections. An increased formation of atypical dense bodies (ADB), a temporary pronounced lipid accumulation and changes of the rough and smooth endoplasmic reticulum were prominent features of subacute GalN intoxication. The implications with respect to a modified GalN action in subacute GalN intoxication are discussed with special reference to biochemical data obtained in the same experimental model (Schuchhardt et al., 1977).
{ "pile_set_name": "PubMed Abstracts" }
Meta-analysis of failure-time data with adjustment for covariates. The objective of this study was to present and illustrate a technique for combining failure-time data from various sources, adjusting for differences in case-mix among studies. Based on the proportional-hazards model and the actuarial life-table approach, the method used assumes that the variation across studies is in part due to heterogeneity of the case-mix and adjusts for the case-mix before pooling results. As an example, the technique is applied to life-table data from six selected papers reporting patency of affected arteries following femoropopliteal angioplasty. Published 4- and 5-year patency results ranged from 25% to 58%, with a pooled five-year cumulative patency rate (without adjustment for case-mix) of 45% (+/- 2%). The populations in these studies, however, differed markedly in the prevalence of factors with prognostic value: type of lesion and distal runoff vessels. After adjustment for these differences in case-mix, the pooled five-year patency rates ranged from 60% (+/- 2%) for patients with stenotic lesions and good runoff to 24% (+/- 9%) for those with occlusion and poor runoff. The authors conclude that pooling studies without considering the effect of case-mix yields an average result with inappropriately narrow confidence intervals that does not reflect the variability across subgroups. The presented technique provides a method for combining failure-time data, adjusting for case-mix.
{ "pile_set_name": "PubMed Abstracts" }
The effects of lactic acid production on contraction and intracellular pH during hypoxia in cardiac muscle. During hypoxia cardiac contraction declines and there is an intracellular acidosis. We find that, if this acidosis is abolished by decreasing pCO2 there is little restoration of force. Therefore the acidosis is not the major cause of the decline of force. The acidosis may partly result from the generation of lactic acid. No acidosis, is however, seen in isolated cardiac cells. Furthermore a theoretical model shows that lactic acid production would be expected to produce a transient acidosis. We suggest that the observed maintained acidosis may be a consequence of extracellular lactic acid accumulation affecting intracellular pH.
{ "pile_set_name": "PubMed Abstracts" }
Ecto-alkaline phosphatase considered as levamisole-sensitive phosphohydrolase at physiological pH range during mineralization in cultured fetal calvaria cells. Alkaline phosphatase (ALP) activity expressed on the external surface of cultured fetal rat calvaria cells and its relationship with mineral deposition were investigated under pH physiological conditions. After replacement of culture medium by assay buffer and addition of p-nitrophenyl phosphate (pNPP), the rate of substrate hydrolysis catalyzed by whole cells remained constant for up to seven successive incubations of 10 min and was optimal over the pH range 7.6-8.2. It was decreased by levamisole by a 90% inhibition at 1 mM which was reversible within 10 min, dexamisole having no effect. Values of apparent Km for pNPP were close to 0.1 mM, and inhibition of pNPP hydrolysis by levamisole was uncompetitive (Ki = 45 microM). Phosphatidylinositol-specific phospholipase C (PI-PLC) produced the release into the medium of a p-nitrophenyl phosphatase (pNPPase) sensitive to levamisole at pH 7.8. The released activity whose rate was constant up to 75 min represented after 15 min 60% of the value of ecto-pNPPase activity. After 75 min of PI-PLC treatment the ecto-pNPPase activity remained unchanged despite the 30% decrease in Nonidet P-40-extractable ALP activity. High levels of 45Ca incorporation into cell layers used as index of mineral deposition were decreased by levamisole in a stereospecific manner after 4 h, an effect which was reversed within 4 h after inhibitor removal, in accordance with ecto-pNPPase activity variations. These results evidenced the levamisole-sensitive activity of a glycosylphosphatidylinositol-anchored pNPPase consistent with ALP acting as an ecto-enzyme whose functioning under physiological conditions was correlated to 45Ca incorporation and permit the prediction of the physiological importance of the enzyme dynamic equilibrium at the cell surface in cultured fetal calvaria cells.
{ "pile_set_name": "PubMed Abstracts" }
Nuchal translucency measurement in first trimester Down syndrome screening. (1) Approximately three in every four fetuses with Down syndrome have increased nuchal translucency (NT), which is a larger than normal build-up of fluid at the back of the neck. (2) The ultrasound measurement of NT between 11 and 14 weeks' gestation, in combination with the mother's age and the levels of placental biochemical markers in her blood, can be used to detect approximately 84% of fetuses with Down syndrome. (3) The accuracy of NT measurement is affected by fetal position, measurement technique, the type of risk-calculation software used, and the sonographer's experience and technical expertise. (4) A rigorous standardization and quality assurance system for NT measurement is needed before any test using NT ultrasound is offered universally. The cost of establishing such a program is unknown.
{ "pile_set_name": "PubMed Abstracts" }
Serum immunoglobulin E in atopic and non-atopic children aged 6 months to 5 years. A follow-up study. In order to obtain serum IgE reference values for small children we measured the total serum IgE concentration at the ages of 6 months, 1, 3, and 5 years in 66 healthy, non-atopic children who were followed from birth to 5 years of age. From this reference group we had excluded children with symptoms or signs of atopy during the follow-up period, as well as children with blood or nasal smear eosinophilia or positive skin prick tests. We also studied serum IgE levels in groups of children having latent atopy, symptomatic atopy, or severe atopic disease. We suggest that in the definition of reference values the upper limit of normal should be replaced by a zone of uncertainty, lying between the 95th and 97.5th percentiles. Serum IgE is a useful test with high specificity but low sensitivity in the differentiation between atopy and non-atopy. Thus high levels suggest atopy, while normal or low values yield little information. A normal serum IgE level does not necessarily exclude atopic disease.
{ "pile_set_name": "PubMed Abstracts" }
The anti-reproductive pharmacology of LH-RH and agonistic analogues. LH-RH and three particular ("super") analogues were evaluated for agonistic (ovulation-induction and short-term uterotrophic properties) and postcoital contraceptive activity in rodents. Additionally, LH-RH and/or a representative analogue (D-Ala6-des Gly10-Pro9-LH-RH ethylamide) were tested for postcoital contraceptive/vaginal smear/return to fertility effects, precoital contraceptive activity, and effects on puberty in the immature female. All compounds induced ovulation and uterotrophic effects and terminated pregnancy when administered either pre- or post-implantation. LH-RH and the representative analogue, while terminating pregnancy postcoitally, produced an associated break in the characteristic leucocytic vaginal smear of pregnancy to one of cornification by day 12; at this time mating and insemination were reestablished and all rats carried to normal term. Precoitally, LH-RH administered to nembutalized (but not to unblocked) rats produced a 50% reduction in the pregnancy rate and a 38% decrease in the number of viable pups delivered. In immature rats, the representative analogue delayed puberty (i.e. vaginal canalization) and retarded the growth of the ovaries, uteri, and anterior pituitary gland. The collective data strongly support the concept that LH-RH and agonistic derivatives, in spite of their putative pro-fertility classification, are characteristically antifertility by nature. Since the latter effect appears to be the paradoxically dominant one, it is suggested that LH-RH agonism is synonymous with contraception. Furthermore, such peptides may represent a new potential approach to fertility control.
{ "pile_set_name": "PubMed Abstracts" }
Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects. Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.
{ "pile_set_name": "PubMed Abstracts" }
p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. In normal human fibroblasts, cyclin A-CDK2 exists in a quaternary complex that contains p21 and PCNA. In many transformed cells, p21 disappears, and a substantial fraction of cyclin A-CDK2 complexes with p9CKS1/CKS2, p19, and p45. To investigate the significance of these rearrangements, we have isolated cDNAs encoding p19 and p45. In vitro reconstitution demonstrated that binding of p19 to cyclin A-CDK2 requires p45. Addition of these proteins to the kinase had no substantial effect on the kinase activity in vitro. Interference with p45 function in vivo by microinjection of antibodies or antisense oligonucleotides prevented entry into S phase in both normal and transformed cells. Cyclin A-CDK2 has previously been identified as a kinase whose activity is essential for S phase. Our results identify p45 as an essential element of this activity. The abundance of p45 is greatly increased in many transformed cells. This could result in changes in cell cycle control that contribute to the process of cellular transformation.
{ "pile_set_name": "PubMed Abstracts" }
L-selectin blockade and liver function in rats after uncontrolled hemorrhagic shock. Hemorrhagic shock (HS) and resuscitation can be seen as a global body ischemia-reperfusion (I/R) injury characterized by neutrophil infiltration and organ damage. Liver dysfunction occurs early after HS. Adhesion molecules are needed for the first steps ofneutrophil migration. Thus, the purpose of this study was to investigate the role of L-selectin in the liver after uncontrolled HS and resuscitation. Forty-eight Sprague Dawley rats were subjected to uncontrolled HS and resuscitation. Animals were divided into three groups: sham, uncontrolled HS and resuscitation, and uncontrolled HS and resuscitation with anti-L-selectin treatment. At 6 we evaluated liver injury tests, liver tissue myeloperoxidase (MPO), and liver histology. Survival was followed for 3 days and compared between groups. Statistical analysis included Fisher's exact test and one-way analysis of variance. Survival significantly increased from 30% in the control group to 60% in the treated group (p < .05). Hepatocellular and structural injury as well as neutrophil infiltration was significantly decreased in treated animals (p < .05). Thus, blockade of L-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.
{ "pile_set_name": "PubMed Abstracts" }
[Effect of TGF-beta1 on epithelial-mesenchymal transition of rat peritoneal mesothelial cells and its mechanism]. To explore the effect of transforming growth factor beta1 (TGF-beta1) on epithelial-mesenchymal transition in rat peritoneal mesothelial cells(RPMCs) and its mechanism. Primary peritoneal mesothelial cells of SP rats were cultured in vitro. After synchronization for 24 h, RPMCs were randomly divided into 2 groups: Group A (control), Group B (TGF-beta1, 10 mug/L). RPMCs were stimulated by 10 mug/L TGF-beta1 for different time. The mRNA and protein expression levels of E-cadherin, alpha-smooth muscle actin (alpha-SMA) and collagen I were measured by RT-PCR and Western blot, respectively. The protein expression level of total RhoA was measured by Western blot. Active RhoA was extracted by Plasma Membrane Protein Extraction Kit, and assessed by Western blot. TGF-beta1 down-regulated mRNA and protein expression of E-cadherin in RPMCs, and upregulated mRNA and protein expression of alpha-SMA and CollagenI. TGF-beta1 stimulation elicited a robust increase in RhoA activity in a time-dependent manner. RhoA activity peaked at 1 h. RPMCs can be transdifferentiated into myofibroblast under the effect of TGF-beta1,and the mechanism may be related to the activation of RhoA associated signal pathway.
{ "pile_set_name": "PubMed Abstracts" }
Comparison of the antibacterial activity of different self-etching primers and adhesives. The aim of this study was to evaluate the antibacterial effects of different one-step and two-step self-etching primer/adhesives on Streptococcus mutans (S. mutans), Lactobacillus casei (L. casei), and Lactobacillus acidophilus (L. acidophilus). The antibacterial effects of Clearfil Protect Bond Primer and Bonding agent; AdheSE Primer and Bonding agent; Adper Prompt L-Pop; Futurabond NR; Clearfil Tri S Bond; and Cervitec (positive control, 1% chlorhexidine varnish) were tested against standard strains of S. mutans, L. Casei, and L. acidophilus using the disk diffusion method. Standard filter paper disks (n=5) impregnated with 20 microL of each material were prepared. After incubation at 37 masculineC for 48 hours in a 5-10% CO2 atmosphere, the diameter of inhibition zones were measured in millimeters. Data were analyzed using one way analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA). Duncan's Multiple Range Test was used for pairwise comparison. The size of inhibition zones produced by primer/adhesives varied among the brands. AdheSE Primer: S. mutans (20.6+/-1.51); L. casei (14.8+/-1.78); L. acidophilus (11.4+/-0.54). Adper Prompt L-Pop: S. mutans (19.6+/-1.51); L. casei (13.8+/-1.64); L. acidophilus (13.8+/-1.09). Cervitec: S. mutans (23+/-0.00); L. casei (27+/-0.70); L. acidophilus (22.4+/-0.54). Clearfil Protect Bond Primer: S. mutans (17+/-0.00); L. casei (17.6+/-0.54); L. acidophilus (22.4+/-0.54). Futurabond NR was found effective only against S. mutans (14.6+/-1.67). Of all the materials tested, AdheSE Bonding agent, Clearfil Protect Bond Bonding agent, and Clearfil Tri S Bond exhibited no inhibition zone (-) for all bacteria tested. Among the adhesives tested Clearafil Protect Bond Primer based upon monomer methacryloyloxydodecylpyridiniium bromide (MDPB) was found to be the most potent material against L. acidophilus and L. casei. AdheSE Primer and Adper Prompt L-Pop are highly effective against S. mutans. Compared with other adhesive systems, Clearfil Protect Bond Primer (containing MDPB) showed a high antibacterial effect against all microorganizms tested. Two-step, self-etching primer/adhesive system Clearfil Protect Bond might be a suitable choice under minimally invasive restorations. The recently developed one-step, self-etching system Clearfil Tri S Bond showed no antibacterial effect against microorgazims tested.
{ "pile_set_name": "PubMed Abstracts" }
Outcome of mantle cell lymphoma patients treated at a single institution over the past decade. Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma entity with a heterogeneous clinical presentation. Various therapeutic considerations in MCL for younger and elderly patients were used over the past decade. We retrospectively analyzed all 44 patients consecutively treated in a tertiary hospital between 2000 and 2010 with newly diagnosed MCL. Patient characteristics, treatment regimens and biological markers were evaluated with regard to overall survival (OS). Treatment regimens were categorized into internationally accepted intensive standard therapies and less intensive alternative treatment regimens given with palliative intent. Biological markers were correlated with clinical outcome by univariate analysis. The median age of the entire study group was 66 years (range: 42-88), with 23 (52%) patients ≥65 years. Thirty-one (70%) patients received standard regimens, the remaining 13 (30%) patients were treated with other, less intensive regimens with palliative intent. With a median follow-up of 5.25 years, the three-year OS rate was 60% [95% confidence interval (CI) 0.47-0.77]. Patients treated with standard regimens had a three-year survival rate of 77% (range: 64-94%). Of these, patients younger than 65 years were observed to have better OS (83% at 3 years; 95% CI 68-100%) than those older than 65 years (69% at 3 years; 95% CI 48-99%). In univariate analysis, the only parameters with a statistically significant prognostic impact on OS were absolute monocyte count as a continuous variable, lactate dehydrogenase and absolute lymphocyte count (>0.5 × 10(9) /l) at diagnosis. In conclusion, our data of an unselected group of patients with newly diagnosed MCL treated at a single centre tertiary hospital are in line with results from larger randomized trials demonstrating an improved OS rate of younger as well as elderly MCL patients within the last decade.
{ "pile_set_name": "PubMed Abstracts" }
Assembly of cytoskeletal proteins into cleavage furrows of tissue culture cells. We review results obtained after fluorescent actin and myosin II probes were microinjected into interphase and prophase PtK2 and LLC-PK tissue culture cells to follow the changing distribution of these cytoskeletal proteins in the live cells during division. The fluorescent probes first begin to assemble into the future furrow region during mid-anaphase before any sign of initial contractions. The total concentrations of F-actin and myosin in the cleavage furrow begin to decrease a few minutes after the onset of furrow contraction. The cell's shape and the position of its mitotic spindle affect the deposition of cytoskeletal proteins in the forming cleavage furrow. In cells with two spindles, contractile proteins were recruited not only to the cortex bordering the former metaphase plates but also to the cortex midway between each pair of adjacent non-daughter poles or centrosomes. The furrowing between adjacent poles seen in these cultured cells are similar to the furrows observed by Rappaport [(1961) J Exp Zool 148:81-89] when echinoderm eggs were manipulated into a torus shape so that the poles of two mitotic spindles were adjacent to one another. These observations on injected tissue culture cells suggest that vertebrate cells share common mechanisms for the establishment of the cleavage furrow with echinoderm cells.
{ "pile_set_name": "PubMed Abstracts" }
Episodic memory and executive functioning in informal dementia caregivers. Objectives: Informal dementia caregivers are thought to experience high levels of depression and burden, which can contribute to worse cognitive functioning. However, poorer cognitive functioning in caregivers is not always found. The current study explored whether caregivers perform better, worse, or similar to non-caregivers on tasks for executive functioning and memory. Whether sociodemographic and psychosocial characteristics are associated with caregivers' performance was also assessed. Methods: One hundred forty-five caregivers completed the Letter Fluency and Category Fluency, the Logical Memory test from the WMS-III, and five questionnaires assessing psychological characteristics. Standardized z-scores (based on age, education, and sex) were calculated using data from a matched control group (187 non-caregivers). One sample z-tests were executed to examine if the caregivers' standardized mean z-score significantly deviated from the population mean of z = 0. The z-scores were used as dependent variables in multivariable regression analyses. Results: The caregivers performed significantly better on Logical Memory - Immediate Recall than non-caregivers (z = 2.92, p = .004). The obtained z-scores on the other tasks did not deviate significantly from 0. Male sex and social reliance predicted higher scores on Category Fluency, but the F-test was non-significant, and the explained variance was low (adjusted R2 = .068). Conclusions: We found no evidence for poorer cognitive performance among informal caregivers compared to non-caregivers. Our results suggest that caregiving for a loved one with dementia does not impair the caregivers' episodic memory or executive functioning when measured cross-sectionally.
{ "pile_set_name": "PubMed Abstracts" }
Tensile radial stress in the spinal cord related to arachnoiditis or tethering: a numerical model. Spinal arachnoiditis comprises fibrous scarring of the subarachnoid space, following spinal trauma or inflammation, and is often associated with syringomyelia. We hypothesised that cord-to-dura attachments could cause transient tensile cord radial stress, as pressure waves propagate. This was tested in a fluid-structure interaction model, simulating three types of cord tethering, with 'arachnoiditis' confined to a short mid-section of the cord. The annular system was excited abdominally with a short transient, and the resulting Young and Lamb waves and reflections were analysed. Radial mid-section tethering was less significant than axial tethering, which gave rise to tensile radial stress locally when the cord was not fixed cranially. Simulated as inextensible string connections to the dura, arachnoiditis caused both localised tensile radial stress and localised low pressure in the cord as the transient passed. The extent of these effects was sensitive to the relative stiffness of the dura and cord. Tensile radial stress may create a syrinx in previously normal cord tissue, and transiently lowered pressure may draw in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited. The suggested mechanism could also explain the juxtaposition of syrinxes to regions of arachnoiditis.
{ "pile_set_name": "PubMed Abstracts" }
Postradiation pleomorphic malignant fibrous histiocytoma of the breast. A case of primary malignant fibrous histiocytoma (MFH) of the breast occurring two years after surgical excision and radiation therapy for a carcinoma of the left breast is reported. Fine needle aspiration was positive for malignant cells, consistent with a pleomorphic sarcoma. Cytologic examination revealed giant cells with marked pleomorphism. Some cells showed single large nuclei with cytoplasmic vacuoles while others revealed multinucleation with foamy cytoplasm, phagocytosed erythrocytes and cellular debris. These findings are considered useful in the cytologic diagnosis of the pleomorphic variant of MFH.
{ "pile_set_name": "PubMed Abstracts" }
Early-stage small-bowel adenocarcinoma: a review of local endoscopic therapy. Early adenocarcinomas in the small intestine are a rare entity. Most adenocarcinomas in the small intestine are diagnosed at a more advanced stage. After surgical resection, only 3 - 10 % are found in stage T1 and 0 - 3 % in stage Tis (high-grade intraepithelial neoplasia), resulting in an overall 3 - 13 % rate of early-stage small-intestinal adenocarcinomas. The diagnosis of early small-intestinal carcinoma by endoscopy is still very rare, although it will probably improve with the development of new endoscopic techniques. At present there have been only two studies and a few case reports on the treatment of early duodenal carcinoma by endoscopic resection. No major complications such as massive bleeding or perforation occurred in the studies and case reports, which show that endoscopic resection is a safe and effective treatment for early duodenal cancers that have not invaded the submucosa. Endoscopic resection can be carried out with reduced costs and lower morbidity and mortality rates in comparison with surgery.
{ "pile_set_name": "PubMed Abstracts" }
[Practice of intranasal allergic tests under rhinorheomanometric control (author's transl)]. The present report describes the method of rhinorheomanometry in intranasal allergic tests, how it is practised at the ENT-Clinic of Heidelberg University. In addition, we give a survey of the steps taken in order to diagnose rhinitis allergica, and explain particularly the necessity of the differentiation from non-allergical reactions as well as of histaminic control. These examinations are illustreated by describing serveral cases.
{ "pile_set_name": "PubMed Abstracts" }
Diffuse Lewy body disease presenting as multiple system atrophy. The majority of patients with diffuse Lewy body disease have cognitive or psychiatric manifestations as part of their initial presentation. A sizable minority present with parkinsonian features alone. Autonomic features may also occur, typically after the development of cognitive changes. We aim to demonstrate that diffuse Lewy body disease may rarely also present with parkinsonism accompanied by marked autonomic dysfunction in the absence of significant cognitive or psychiatric abnormalities. Case report based on a retrospective chart review and neuropathological examination. We report on a patient in whom a clinical diagnosis of multiple system atrophy was made based on a presentation of parkinsonism with prominent and early autonomic involvement. The former included postural tremor, rigidity and bradykinesia, while the latter consisted of repeated falls due to orthostasis and the subsequent development of urinary incontinence midway through the course of her illness. She was poorly tolerant of dopaminergic therapy due to accentuated orthostasis. Benefit from levodopa was limited and only evident when attempted withdrawal resulted in increased rigidity. There was no history of spontaneous or drug-induced hallucinations, delusions or fluctuating cognition, and in contrast to the prominence and progression of her parkinsonian and autonomic features over the first several years, cognitive impairment did not occur until the final stages of her illness, seven years after the onset of initial symptoms. Neuropathological examination revealed numerous Lewy bodies in both neocortical as well as subcortical structures consistent with a diagnosis of diffuse Lewy body disease. There was marked neuronal loss in the substantia nigra as well as the autonomic nuclei of the brainstem and spinal cord. In addition to cognitive, psychiatric, and parkinsonian presentations, diffuse Lewy body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA.
{ "pile_set_name": "PubMed Abstracts" }
Anti-inflammatory therapy in Alzheimer's disease: is hope still alive? Based on observations from neuropathology, epidemiology, and in vitro and animal experiments, the inflammatory component of Alzheimer's disease (AD) has been considered a compelling target for therapeutic intervention. However, a summary of all published trial reports to date suggests that AD patients do not benefit from treatment with anti-inflammatory drugs. In this brief review, we try to reconcile these sobering trial results with recent observations from basic research and epidemiology that continue to strengthen the idea that inflammatory mechanisms play an important role in the pathogenesis of AD. We review the possibilities that (1) not all components of the inflammatory response in AD are detrimental, (2) beneficial effects of anti-inflammatory drugs may not be mediated by inflammatory pathways, and (3) the timing of the intervention should be in the earliest stages of the pathogenesis of AD, perhaps even before the first symptoms emerge. We conclude that studies on primary prevention of AD are the logical next step in testing the inflammatory hypothesis of AD.
{ "pile_set_name": "PubMed Abstracts" }
Alveolar bone loss in rats infected with a strain of Prevotella intermedia and Fusobacterium nucleatum isolated from a child with prepubertal periodontitis. Prevotella intermedia and fusobacterium nucleatum are associated with various forms of periodontal disease. The purpose of the present study was to infect the clinical isolates of these periodontopathic bacteria and to induce a significant loss of alveolar bone in specific pathogen-free (SPF) rats in the absence of ligatures. P. intermedia YKD8 and F. nucleatum YKZ5 were isolated from a prepubertal periodontitis patient, while P. gingivalis MWB13 was from a patient with juvenile periodontitis. At first, SPF Sprague-Dawley rats (70 days of age, male) were infected with A. viscosus Ny1R and subsequently superinfected with P. gingivalis MWB13, P. intermedia YKD8, or F. nucleatum YKZ5, respectively. The control group was infected with A. viscosus Ny1R alone. All rats were killed and periodontal bone levels were assessed morphometrically 135 days after the first infection with A. viscosus. P. intermedia YKD8 was recovered frequently from rats, with serum antibody levels remaining highly elevated throughout the experiment. Significant loss of alveolar bone was found in rats infected with P. intermedia YKD8, the virulence of which was equivalent to that of P. gingivalis MWB13. F. nucleatum YKZ5 also induced alveolar bone loss, but not significantly when compared with rats infected with A. viscosus Ny1R alone.
{ "pile_set_name": "PubMed Abstracts" }
Geographical Inequality in Tobacco Control in China: Multilevel Evidence From 98 058 Participants. We investigated the spatial patterning and correlates of tobacco smoking, exposure to secondhand smoke, smoking in public places, workplace smoking prohibition, pro- and counter-tobacco advertisements in mainland China. Choropleth maps and multilevel models were used to assess geographical variation and correlates of the aforementioned outcome variables for 98 058 participants across 31 provinces of China in 2010. Current tobacco smoking prevalence was higher in the central provinces for men and in the north eastern provinces and Tibet for women. Secondhand smoke was higher for both genders in Qinghai and Hunan provinces. Workplace tobacco restrictions was higher in the north and east, whereas smoking in public places was more common in the west, central, and far northeast. Protobacco advertising was observed in public places more often by men (18.5%) than women (13.1%). Men (35.5%) were also more likely to sight counter-tobacco advertising in public places than women (30.1%). Awareness of workplace tobacco restrictions was more common in affluent urban areas. Lower awareness of workplace tobacco restrictions was in less affluent urban and rural areas. Sightings of tobacco smoking in public places was highest in restaurants (80.4% for men, 75.0% for women) and also commonly reported in less affluent urban and rural areas. Exposure to secondhand smoke was lower among women (but not men) where workplace tobacco restrictions was more common and higher regardless of gender in areas where smoking in public places was more commonly observed. Geographical and gender-sensitive targeting of tobacco prevention and control initiatives are warranted. This study demonstrates spatial patterning of China's 300 million smokers across the country that are different for men and women. Many of the factors that influence tobacco use, such as pro- and counter-advertising, also vary geographically. Workplace smoking restrictions are more commonly reported among individuals with higher educational attainment, but this not does appear to translate into reduced exposure to secondhand smoke. There is a need to intervene in other contexts, especially in restaurants and on public transport. Geographically targeted and gender-sensitive policy is required to advance effective tobacco control and prevention of noncommunicable diseases across all of China.
{ "pile_set_name": "PubMed Abstracts" }
The medical mystery of Napoleon Bonaparte: an interdisciplinary exposé. Napoleon Bonaparte (1769 to 1821) is one of the most studied historical figures in European history. Not surprisingly, amongst the many mysteries still surrounding his person is the cause of his death, and particularly the suspicion that he was poisoned, continue to intrigue medical historians. After the defeat of the Napoleonic Army at the battle of Waterloo in 1815, Napoleon was exiled to the small island of Saint Helena in the South Atlantic, where he died 6 years later. Although his personal physician, Dr François Carlo Antommarchi, stated in his autopsy report that stomach cancer was the cause of death, this diagnosis was challenged in 1961 by the finding of an elevated arsenic concentration in one of Napoleon's hair samples. At that time it was suggested that Napoleon had been poisoned by one of his companions in exile who was allegedly supported by the British Government. Since then Napoleon's cause of death continues to be a topic of debate. The aim of this review is to use a multidisciplinary approach to provide a systematic and critical assessment of Napoleon's cause of death.
{ "pile_set_name": "PubMed Abstracts" }
Atopic dermatitis and food hypersensitivity reactions. To determine the role of food hypersensitivity in atopic dermatitis and to determine whether patients with atopic dermatitis who had food hypersensitivity could be identified by screening prick skin tests using a limited number of food allergens. Patients with atopic dermatitis attending the Arkansas Children's Hospital Pediatric Allergy Clinic underwent allergy prick skin testing to a battery of food antigens. Patients with positive prick skin tests underwent double-blind, placebo-controlled food challenges. One-hundred sixty-five patients were enrolled and completed the study. Patients ranged in age from 4 months to 21.9 years (mean 48.9 months). Ninety-eight (60%) patients had at least one positive prick skin test. A total of 266 double-blind, placebo-controlled food challenges were performed. Sixty-four patients (38.7% of total) were interpreted as having a positive challenge. Seven foods (milk, egg, peanut, soy, wheat, cod/catfish, cashew) accounted for 89% of the positive challenges. By use of screening prick skin tests for these seven foods we could identify 99% of the food allergic patients correctly. This study confirms that most children with atopic dermatitis have food allergy that can be diagnosed by a prick skin test for the seven foods.
{ "pile_set_name": "PubMed Abstracts" }
Investigation of self-phase modulation based optical regeneration in single mode As2Se3 chalcogenide glass fiber. We investigate the feasibility of all-optical regeneration based on self-phase modulation in single mode As2Se3 chalcogenide fiber. By combining the chalcogenide fiber with a bandpass filter, we achieve a near step-like power transfer function with no pulse distortion. The device is shown to operate with 5.8 ps duration pulses, thus demonstrating the feasibility of this device operating with high bit-rate data signals. These results are achieved with pulse peak powers <10 W in a fully passive device, including only 2.8 m of chalcogenide fiber. We obtain an excellent agreement between theory and experiment and show that both the high nonlinearity of the chalcogenide glass along with its high normal dispersion near 1550 nm enables a significant device length reduction in comparison with silica-based devices, without compromise on the performance. We find that even for only a few meters of fiber, the large normal dispersion of the chalcogenide glass inhibits spectral oscillations that would appear with self-phase modulation alone. We measure the two photon absorption attenuation coefficient and find that it advantageously affects the device transfer function.
{ "pile_set_name": "PubMed Abstracts" }
Medium-throughput production of recombinant human proteins: ligation-independent cloning. Structural genomics groups have identified the need to generate multiple truncated versions of each target to improve their success in producing a well-expressed, soluble, and stable protein and one that crystallizes and diffracts to a sufficient resolution for structural determination. At the SGC, we opted for the Ligation-Independent Cloning (LIC) method which provides the medium throughput we desire to produce and screen many proteins in a parallel process. Here, we describe our LIC protocol for generating constructs in a 96-well format and provide a choice of vectors suitable for expressing proteins in both E. coli and the baculovirus expression vector system (BEVS).
{ "pile_set_name": "PubMed Abstracts" }
Donor-to-host transmission of streptococcal infection by corneas stored in McCarey-Kaufman medium. Two patients developed streptococcal endophthalmitis following penetrating keratoplasty. These cases may represent the third and fourth cases of donor-to-host transmission of streptococcal infection by corneas stored in McCarey-Kaufman (M-K) medium. Streptococcal agents now account for 50-59% of the total number of reported cases of M-K medium contamination by donor tissue with resultant infection in the host. Gentamicin sulfate, the sole antibiotic used in the M-K medium in all cases, has poor activity against most streptococci. The addition of a second antibiotic to the M-K medium to provide an improved spectrum of antimicrobial activity should be considered.
{ "pile_set_name": "PubMed Abstracts" }
One-year outcome after percutaneous rotational and aspiration atherectomy in infrainguinal arteries in patient with and without type 2 diabetes mellitus. To compare the safety and efficacy of a rotational aspiration atherectomy system (Jetstream) for the treatment of infrainguinal arteries in diabetic versus nondiabetic patients. A total of 172 patients with Rutherford stage 1-5 lower limb ischemia were treated with rotational aspiration atherectomy between February 2006 and February 2007. Of these, 80 patients with type 2 diabetes mellitus (DM: 46.5%) were compared with 92 nonDM (53.5%) patients. Overall, 210 target lesions (99 DM; 111 nonDM) were treated, located in the superficial femoral (67% DM; 61% nonDM), popliteal (25% DM; 30% nonDM), and tibial (8% DM; 9% nonDM) arteries. Lesion characteristics were comparable in both groups, mean lesion length was 28.5 mm (DM) and 26.2 mm (nonDM); total occlusions were present in 29% (DM) and 32% (nonDM), and 15% (DM) and 14% (nonDM) were restenotic. In the entire cohort, device success was 99% (all but two lesions). The major adverse event (MAE) rate (death, index limb amputation, myocardial infarction, target lesion revascularization [TLR] and target vessel revascularization) in DM at 30 days was 2.5% (n = 2 planned amputations) and 0% in nonDM. At 6 and 12 months, MAE in DM was seen in 13.8% (11/80) and 25% (20/80) compared with 21.7% (20/92) and 31.5% (29/92) in nonDM, respectively. TLR rate through 12 months was 20% (16/80) in DM and 28% in nonDM (26/92). Overall, 1 year restenosis rate was 38.2% based on duplex. The ankle-brachial index, mean Rutherford categories, and walking impairment questionnaire did not differ between groups at baseline and were increased significantly in both study cohorts at 12 months. Jetstream-assisted atherectomy in infrainguinal arteries is safe and effective in DM compared with nonDM patients. In this short-lesion cohort, vessel patency in diabetics was as good as for non-DM at 1 year. TLR and MAE were higher by trend in nonDM, although planned amputations were seen only in DM. The clinical benefit was similar in both groups.
{ "pile_set_name": "PubMed Abstracts" }