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Production of surfactin and fengycin by Bacillus subtilis in a bubbleless membrane bioreactor.
Surfactin and fengycin are lipopeptide biosurfactants produced by Bacillus subtilis. This work describes for the first time the use of bubbleless bioreactors for the production of these lipopeptides by B. subtilis ATCC 21332 with aeration by a hollow fiber membrane air-liquid contactor to prevent foam formation. Three different configurations were tested: external aeration module made from either polyethersulfone (reactor BB1) or polypropylene (reactor BB2) and a submerged module in polypropylene (reactor BB3). Bacterial growth, glucose consumption, lipopeptide production, and oxygen uptake rate were monitored during the culture in the bioreactors. For all the tested membranes, the bioreactors were of satisfactory bacterial growth and lipopeptide production. In the three configurations, surfactin production related to the culture volume was in the same range: 242, 230, and 188 mg l(-1) for BB1, BB2, and BB3, respectively. Interestingly, high differences were observed for fengycin production: 47 mg l(-1) for BB1, 207 mg l(-1) for BB2, and 393 mg l(-1) for BB3. A significant proportion of surfactin was adsorbed on the membranes and reduced the volumetric oxygen mass transfer coefficient. The degree of adsorption depended on both the material and the structure of the membrane and was higher with the submerged polypropylene membrane. | {
"pile_set_name": "PubMed Abstracts"
} |
Haplotype block and superblock structures of the alpha1-adrenergic receptor genes reveal echoes from the chromosomal past.
A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origins of haplotype block structure in the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome ( ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block 1 is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both ADRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data. | {
"pile_set_name": "PubMed Abstracts"
} |
Hydroxycamptothecin deactivation rates and binding to model membranes and HSA determined by fluorescence spectra analysis.
Camptothecins (CPTs) are fluorescent compounds exhibiting anticancer activity. They can exist in two forms, a lactone and a carboxylate. In neutral and base solution, lactone forms hydrolyse and convert into carboxylates. Only the lactone forms of CPTs are biologically active. Because of strong affinity of the carboxylate form of the parent drug camptothecin to human serum albumin (HSA), this protein promotes the deactivation of this compound. On the other hand, the lactone forms of camptothecins do not hydrolyse and are stabilized when bound to membranes. The following three hydroxycamptothecins, 10 hydroxycamptothecin (10-OH-CPT), 7-ethyl-10-hydroxy-camptothecin (SN-38) and 7-tert-butyldimethylsil-10-hydroxycamptothecin (DB-67) were studied. Factor analysis of a set of fluorescence excitation spectra recorded during lactone hydrolysis facilitated the high-throughput determination of the deactivation rates of camptothecin and each hydroxycamptothecin in phosphate buffered saline. The fluorescence spectra of hydroxycamptothecins diluted in HSA solution or suspended in DMPC liposomes were recorded, and the association constants of these drugs to membranes and plasma proteins were calculated. Among the analysed agents, DB-67 exhibited the most desirable properties including low affinity of the carboxylate form for albumin and high affinity of its lactone form for model membranes. | {
"pile_set_name": "PubMed Abstracts"
} |
Peptide pores in lipid bilayers: voltage facilitation pleads for a revised model.
We address the problem of antimicrobial peptides that create pores in lipid bilayers, focusing on voltage-temperature dependence of pore opening. Two novel experiments (voltage clamp with alamethicin as an emblematic representative of these peptides and neutron reflectivity of lipid monolayer at solid-water interface under electric field) serve to revise the only current theoretical model. We introduce a general contribution of peptide adsorption and electric field as being responsible for an unbalanced tension of the two bilayer leaflets and we claim that the main entropy cost of one pore opening is due to the corresponding excluded area for lipid translation. | {
"pile_set_name": "PubMed Abstracts"
} |
Coupled-mode theory for infrared and submillimeter wave detectors.
We present a comprehensive, spatiotemporal, modal theory of submillimeter-wave and far-infrared power detectors. The theory is based on the contraction of the coherence tensor of the light with another coherence tensor that incorporates all of the physics of the detector. The theory is extremely general and applies to detectors of any bandwidth, with light in any state of polarization and spatiotemporal coherence. The theory applies equally to quasi-monochromatic and pulsed systems. We show that the tensor associated with the detector is a measureable quantity and outline a procedure for its experimental determination. We derive expressions for the statistical properties of a detector's output, including the correlations between the outputs of different detectors, say, in an array or interferometer. The theory provides a clear conceptual understanding of how any general detector couples to the modes of an optical system and thereby provides a powerful and flexible way of modeling the behavior of detectors and instruments. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular cloning, overexpression in Escherichia coli, and purification of 6x his-tagged C-terminal domain of Clostridium difficile toxins A and B.
Genomic DNA from ribotype-01 and -17 Clostridium difficile strains was used for amplification of the sequences encoding the carboxy-terminal domain of toxins A (TcdA) and B (TcdB). The deduced C-terminal TcdB ribotype-01 and -17 domains share 99.5% amino acid sequence identity while TcdA ribotype-17 comprises a 607 amino acid deletion compared to TcdA-01. When compared to previously sequenced C. difficile toxins, 99.3% amino acid identity was found between TcdA-01 and TcdA from strain VPI10643 and 98.8% identity between TcdA-17 and TcdA from strain F-1470. The obtained sequences were fused in 3' to a sequence encoding a hexahistidine tag and cloned into an Escherichia coli expression vector. The recombinant proteins were expressed in E. coli and purified using single-step metal-chelate chromatography. The recombinant carboxy-terminal domain of TcdA-01 was purified from the soluble E. coli lysate fraction whereas TcdA-17 and TcdB-17 carboxy-terminal domains were purified from inclusion bodies. At least 40 mg of each protein was purified per liter of bacterial culture. The recombinant toxin domains were detected specifically by Western blot and ELISA with antibodies against native C. difficile toxins. This study demonstrated that the carboxy-terminal domains of TcdA and TcdB can be produced using an E. coli expression system and easily purified. These recombinant, stable, and non-toxic proteins provide a convenient source for use in the diagnosis of C. difficile infections, instead of native toxins, as controls and calibrators in immunoassay kits and to obtain specific monoclonal antibodies. | {
"pile_set_name": "PubMed Abstracts"
} |
Selected flavonoid compounds as promising inhibitors of protein kinase CK2α and CK2α', the catalytic subunits of CK2.
CK2 is a ubiquitous protein kinase involved in many cell functions. During the last years it became an interesting target in cancer research. A series of flavonoid compounds was tested as inhibitors of protein kinase CK2. Several substances were found to be highly active against both catalytic subunits with IC50 values below 1 μM in case of CK2α'. The most promising inhibitor we identified is chrysoeriol with IC50 values of 250 and 34 nM for CK2α and CK2α', respectively. | {
"pile_set_name": "PubMed Abstracts"
} |
The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis.
Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer prevention. | {
"pile_set_name": "PubMed Abstracts"
} |
Carney's triad: gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma in young females.
The case of a 13-year-old girl with a gastric leiomyosarcoma and a pulmonary osteochondroma is presented. The association of these two tumours and extra-adrenal paraganglioma has been described as a triad by Carney. The patient is free of recurrence of the gastric tumour with no evidence of paraganglioma 10 months after the operation. To our knowledge this is the first case of the triad reported in the UK. | {
"pile_set_name": "PubMed Abstracts"
} |
[In vitro comparison of properties of aortic allotransplants and the Björk-Shiley valve].
The authors performed an in vitro test and compared some hydrodynamic parameters of Björk Shiley valves and aortic allotransplants. Both types of valves are comparable from the aspects of most parameters. The Björk Shiley valve gives some better values with the exception of sufficiency. The great scatter of assessed values in biological valves draws attention to the necessity to make the test before implantation. From the hydrodynamic aspect the authors consider allotransplants valvular prostheses suitable for implantation. Ref. 5, Tab. 1. | {
"pile_set_name": "PubMed Abstracts"
} |
Repeat valvular operations: bench optimization of conventional surgery.
Repeat heart valve operations have become a quite common procedure. We reviewed our experience with reoperative valvular surgery during a 6-year period to assess the risk factors affecting in-hospital mortality and medium-term survival. A series of 316 redo procedures performed on a total of 290 patients in the period between 1997 and 2002 at our institution was retrospectively analyzed. Univariate and multivariable analyses were performed. In-hospital mortality was 3.8%; overall mortality at the end of a 30-month follow-up was 9.3%. We identified advanced New York Heart Association class, advanced age, depressed ejection fraction, emergent or urgent presentation, impairment of renal function, and involvement of tricuspid valve as predictors of mortality. In contrast, duration of cardiopulmonary bypass and multiple valve procedure were not associated with increased short-term risk. The present study is characterized by particular attention in reducing confounding variables and biases correlated to heterogeneities. The main determinants of mortality are related to the degree of patients' illness rather than to inherent technical factors of reoperations. Although highest-risk individuals (previous coronary artery bypass grafting or coexistence of aortic aneurysm) were excluded from the study, our data suggest that patients undergoing isolated redo valvular procedures now face operative risks that are comparable to primary intervention. | {
"pile_set_name": "PubMed Abstracts"
} |
Rainbow trout complement fixation used for titration of antibodies against several pathogens.
Since it is impossible to fix guinea pig complement (C) with Rainbow Trout (Salmo gairdneri) antibodies, whereas it is possible with Brown Trout (Salmo trutta) antibodies, a C fixation test has been designed which uses haemolysin and C from Rainbow Trout. Immunization of trout against lysed sheep red blood cells (SRBC) elicited production of haemolytic IgM. Normal trout serum (NTS) can be used as a source of C at a dilution at which its "natural" haemolytic activity (against various homeotherms RBC) has disappeared. Heating of trout C 30 min at 37 degrees C leads to a 75% loss of its activity, and this one is completely abolished at 40 degrees C. Fixation of 3 to 4 CH50 units has been achieved in a short test (2 h at 20 degrees C) for the following antigen-antibody systems: 2 bacterial antigens (Aeromonas salmonicida and Vibrio anguillarum); 2 viruses (Infectious Pancreatic Necrosis (IPN) virus and Egtved Virus). C fixation has a sensitivity comparable with agglutination in the case of A. salmonicida. For IPN Virus, sero-neutralization is 50 times more sensitive than C fixation. In the case of Egtved virus, the difference is not so great. | {
"pile_set_name": "PubMed Abstracts"
} |
Mean time and first-pass metabolism.
The theoretical principles are outlined for estimating the fraction of a drug undergoing first-pass metabolism using only the plasma levels found after a single oral dose. Data for 3 drugs are used to illustrate the method. It involves analysis of the parent drug and the metabolite formed during the first passage through the gut wall and liver and evaluation of their total mean times. The mean time characteristics of molsidomine, nortriptyline and propranolol are considered and they confirm the theoretically deduced dependency of the mean time of the parent drug and the metabolite. Whether the results are more precise than those obtained from comparison of areas after oral and intravenous administration is discussed. From the data presented it is clear that the mean time method depends on the scatter inherent in the data. In order to estimate the true first-pass effect, greater scatter requires an increased number of data pairs, i.e. subjects. If intravenous data are not available, however, the method described provides a rough but worthwhile estimate of the first pass effect. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical Comparison With Short-Term Follow-Up of Bioresorbable Vascular Scaffold Versus Everolimus-Eluting Stent in Primary Percutaneous Coronary Interventions.
Objective of this study was to assess the clinical performance of bioresorbable vascular scaffold (BVS) compared to everolimus-eluting stent (EES) in subjects with ST-segment elevation myocardial infarction (STEMI). We included all consecutive patients with STEMI who underwent percutaneous coronary intervention (PCI) with BVS implantation in centers participating to the Italian ABSORB Prospective Registry (BVS-RAI) and PCI with EES in the same centers during the same period. The 2 groups were compared. The primary end point was patient-oriented composite end point (POCE) including cardiac death, myocardial infarction, and target lesion revascularization (TLR) at the longest available follow-up. BVS or EES thrombosis at follow-up was also evaluated. Of the 563 patients with STEMI included, 122 received BVS and 441 EES. Procedural success was obtained in 549 (97.5%) cases without significant differences between the 2 groups (BVS 99.3% vs EES 97.0%, p = 0.2). At a median of 220-day (interquartile range 178 to 369) follow-up, no significant differences were observed in terms of POCE (BVS 4.9% vs EES 7.0%, p = 0.4); death (BVS 0.8%, EES 2.0%, p = 0.4), MI (BVS 4.1%, EES 2.0%, p = 0.2), TLR (BVS 4.1%, EES 4.5%, p = 0.8), device thrombosis (BVS 2.5%, EES 1.4%, p = 0.4). All TLR cases were successfully managed with re-PCI in both groups. A propensity matching of the study populations showed no significant differences regarding POCE at the longest available follow-up (odds ratio 0.53, 0.1 to 4.3). In conclusion, in this direct prospective comparison, BVS was associated with similar clinical results compared to EES in the STEMI setting. Larger and adequately powered randomized trials are needed to fully assess the potential clinical benefit of BVS versus the current standard of care in patients with STEMI. | {
"pile_set_name": "PubMed Abstracts"
} |
The membrane dialysis bioreactor with integrated radial-flow fixed bed--a new approach for continuous cultivation of animal cells.
A hybridoma cell was cultivated continuously in a membrane dialysis bioreactor with an integrated radial-flow fixed bed consisting of porous Siran carriers over a period of 6 weeks. Antibodies accumulated to an average of 100 mg l-1, approx. 10 times more than in fixed bed cultures without dialysis membrane. Serum costs could be reduced about 85% due to an appropriate feeding strategy. Siran carriers with 3-5 mm diameter showed an advantage compared to those with 1-2 mm diameter. For the 3-5 mm carrier the specific glucose uptake rate and the MAb production rate were constant, if the velocity was between 0.09 mm s-1 and 0.75 mm s-1. At higher velocities cells are washed out of the bed. Furthermore antibody consistency and cell stability were verified in long-term cultivations over a period of 96 days. From an estimation of the antibody concentration reachable with the reactor concept under optimal conditions a concentration 45 times higher compared to axial-flow fixed bed reactors and 11 times higher compared to stirred tank reactors can be expected. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of long-term hearing gains after stapes surgery with piston reconstruction for otosclerosis.
We sought to assess the postoperative hearing gains at individual frequencies after stapes surgery with piston reconstruction for clinical otosclerosis. We analyzed the air conduction (AC) hearing gains at various audiometric frequencies in a sample of 1,168 stapes procedures with piston reconstruction performed on 911 strictly consecutive patients by one surgeon between 1963 and 1979. Assiduous follow-up of patients was attempted for at least 10 years. The audiometric results over time were stored for computer analysis. The mean AC gain over the speech frequencies (0.5, 1,2, and 3 kHz) was 35.5 dB at 1 year after operation, and the rate of deterioration over the next 19 years was 0.58 dB/y. The picture to emerge from the analysis is clear. The mean AC gain is maximal at nearly 40 dB for the audiometric frequencies of 0.25, 0.5, and 1 kHz. The mean AC gain at any given time after operation decreases with increasing frequency, at least for frequencies of > or = 1 kHz. For any frequency there is, with few exceptions, a significant decrease in the AC gain from one time period to the next. | {
"pile_set_name": "PubMed Abstracts"
} |
Age-related changes in size of the aortic valve annulus in man.
Data previously published in the literature, regarding the size of the aortic valve in man, have been reanalyzed. Aortic valve size increases at a slower rate than the surface area of the human body until maturity is reached at approximately 18 to 21 years of age. After that age, aortic valve size increases nearly linearly with age. There appears to be a slightly faster rate of aortic dilatation in males than in females, but this may be due to errors in estimating body surface area from only height and weight for obviously different body contours. Body surface area, thus, does not seem to be a good normalizing factor for the aortic valve size and the practice of referencing aortic valve sizes to the body surface area size should be discontinued. Alternate forms of using linear regression equations are reported and would appear to be preferable. | {
"pile_set_name": "PubMed Abstracts"
} |
Newly Developed Drugs for Alzheimer's Disease in Relation to Energy Metabolism, Cholinergic and Monoaminergic Neurotransmission.
Current options for Alzheimer's disease (AD) treatment are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or memantine, acting as an N-methyl-D-aspartate (NMDA). Therapeutic approaches vary and include novel cholinesterase inhibitors, modulators of NMDA receptors, monoamine oxidase (MAO) inhibitors, immunotherapeutics, modulators of mitochondrial permeability transition pores (mPTP), amyloid-beta binding alcohol dehydrogenase (ABAD) modulators, antioxidant agents, etc. The novel trends of AD therapy are focused on multiple targeted ligands, where mostly ChE inhibition is combined with additional biological properties, positively affecting neuronal energy metabolism as well as mitochondrial functions, and possessing antioxidant properties. The present review summarizes newly developed drugs targeting cholinesterase and MAO, as well as drugs affecting mitochondrial functions. | {
"pile_set_name": "PubMed Abstracts"
} |
Fetal magnetocardiography using optically pumped magnetometers: a more adaptable and less expensive alternative?
Fetal magnetocardiography provides the requisite precision for diagnostic measurement of electrophysiological events in the fetal heart. Despite its significant benefits, this technique with current cryogenic based sensors has been limited to few centers, due to high cost of maintenance. In this study, we show that a less expensive non-cryogenic alternative, optically pumped magnetometers, can provide similar electrophysiological and quantitative characteristics when subjected to direct comparison with the current technology. Further research can potentially increase its clinical use for fetal magnetocardiography. © 2016 John Wiley & Sons, Ltd. | {
"pile_set_name": "PubMed Abstracts"
} |
Rapid motif compliance scoring with match weight sets.
Most current implementations of motif matching in biological sequences have sacrificed the generality of weight matrix scoring for shorter runtimes. The program MOTIF incorporates a weight matrix and a rapid, backtracking tree-search algorithm to score motif compliance with greatly enhanced performance while placing no constraints on the motif. In addition, any positions within a motif can be marked as 'inviolate', thereby requiring an exact match. MOTIF allows a choice of regular expression formats and can use both motif and sequence libraries as either targets or queries. Nucleic acid sequences can optionally be translated by MOTIF in any frame(s) and used against peptide motifs. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues.
Previous studies have reported the presence of renin mRNAs in several mouse tissues and angiotensinogen mRNAs in various rat tissues. Clarification as to whether renin and angiotensinogen mRNAs are coexpressed in the same tissues of the same animal species is important for understanding the biology of the tissue renin-angiotensin system. We employed mouse renin cDNA and rat angiotensinogen cDNA to compare tissue distributions of renin and angiotensinogen in RNAs of the rat and mouse. Both cDNA probes readily cross-hybridize with the corresponding mRNA of the other species. Our results demonstrate several patterns of distribution. Renin and angiotensinogen mRNAs are readily detected in kidney and adrenals of both species. In brain and heart, angiotensinogen mRNAs are present in concentrations that far exceed renin mRNA levels in these organs in both species. In mouse and rat livers, angiotensinogen, but not renin, mRNA is demonstrated. In rat testis, only renin mRNA can be detected, whereas in mouse testes both renin and angiotensinogen mRNA are present. In CD-1 male mouse submandibular gland, renin mRNA exists in high concentrations, whereas angiotensinogen mRNA is present in low levels. In contrast, neither renin nor angiotensinogen mRNA could be detected in rat salivary gland. In summary, our study demonstrates the widespread codistribution of renin and angiotensinogen mRNAs in many tissues of both species, allowing for the possibility of local angiotensin production. However, tissue and species differences in these gene expressions also exist. Understanding differential tissue expressions of these genes will provide additional important insight into the biology of the renin-angiotensin system. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes in Standard Electroencephalograms Parallel Consciousness Improvements in Patients With Unresponsive Wakefulness Syndrome.
To identify changes in the standard electroencephalograms (EEGs) of patients with unresponsive wakefulness syndrome (UWS) who did or did not recover consciousness 6 months after admission to a rehabilitation department. Prospective cohort study. Unit for severe acquired brain injuries. Consecutive patients with UWS (N=28). Not applicable. EEG amplitude (reduced or normal), dominant frequency (alpha, theta, or delta), and reactivity (absent or present) were scored at admission and 6 months later. The cumulative Amplitude-Frequency-Reactivity score was evaluated. Clinical assessments were made using the Coma Recovery Scale-Revised. Sixteen (57.1%) of the 28 patients with UWS recovered consciousness after 6 months, while 12 patients (42.9%) did not recover consciousness. EEG improvements occurred in 14 patients with consciousness recovery (87.5%) and 2 patients without consciousness recovery (16.7%) only. Improvements in EEG dominant frequency (from the theta to the alpha band or from the delta to the theta band), reappearance of EEG reactivity, and Amplitude-Frequency-Reactivity score increase (P<.01) differentiated patients with consciousness improvement from those without consciousness improvement. Six months after admission for rehabilitation, patients with EEG improvements showed higher Coma Recovery Scale-Revised scores than did those without EEG changes (P<.01). Most patients who emerge from UWS demonstrate improvement in basic EEG characteristics over time. EEG changes in patients with UWS may aid in the timely recognition of patients transitioning into a minimally conscious state. | {
"pile_set_name": "PubMed Abstracts"
} |
A helpline for patients with chronic dermatological conditions.
A telephone line was set up for patients with chronic dermatological diseases in response to patients' concerns about having a point of contact for advice and for more appropriate and timely access to care when they needed to be seen. The aims were firstly to improve the quality of care and empower patients by providing advice and support with a safety net for those discharged from the authors' service. The second aim was to increase efficiency by reducing unnecessary return appointments. An audit was undertaken to evaluate the telephone service. This showed that patients were reassured that they could access the service according to their needs. There was a high level of satisfaction with the initiative and the advice received. The data also showed that there was a significant improvement in the ratio of new outpatient slots to return appointment slots and waiting times for a first appointment. | {
"pile_set_name": "PubMed Abstracts"
} |
Aspergillus helicothrix, sp. nov.
Aspergillus helicothrix sp. nov. is described. The species is based on a single-spore isolate obtained from the type culture of Aspergillus ellipticus Raper et Fennell. It is characterized by conspicuously echinate conidia and cup-shaped sclerotia with coiled setae. | {
"pile_set_name": "PubMed Abstracts"
} |
Bmp7 regulates germ cell proliferation in mouse fetal gonads.
Relatively little is known regarding the signals that regulate the proliferation and sex-specific development of germ cells during mammalian fetal gonad differentiation. Members of the bone morphogenetic protein (BMP) family have been identified as key regulators of germ cells in the Drosophila gonad. Here we show that in mice Bmp7 is expressed in gonads of both sexes and is required for germ cell proliferation during a narrow window of development between 10.5-11.5 days post coitum (dpc). The proliferation defect is more severe in male than in female embryos suggesting that there are sexually dimorphic compensatory pathways. BMP signaling appears to be an evolutionarily conserved pathway regulating embryonic germ cell proliferation in vertebrate and invertebrate species. | {
"pile_set_name": "PubMed Abstracts"
} |
Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats.
Peripheral neuropathy is common and ultimately accounts for significant morbidity in diabetes. Recently, several neurotrophic factors have been used to prevent progression of diabetic neuropathy. In this study, we gave repeated intramuscular injections of the human hepatocyte growth factor (HGF) gene percutaneously, using liposomes containing the hemagglutinating virus of Japan (HVJ), to examine therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal injection of streptozotocin resulted in a marked tactile allodynia (but not in a thermal hyperalgesia), in a reduction of both the conduction velocity and the amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6 weeks after the induction. All these changes were significantly reversed by repeated gene transfer of HGF. Furthermore, we analyzed the density of endoneurial capillaries and morphometrical changes of the nerve. The density of endoneurial capillaries, disclosing marked reduction in diabetic rats, was also reversed significantly by repeated gene transfer of HGF; however, no considerable differences were observed morphometrically in either myelinated or unmyelinated axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of human HGF has potential for the safe effective treatment of diabetic sensorimotor neuropathy. | {
"pile_set_name": "PubMed Abstracts"
} |
Methods for routine biological monitoring of carcinogenic PAH-mixtures.
The ability of a biomarker to provide an assessment of the integrated individual dose following uptake through multiple routes is especially valuable for mixtures of polycyclic aromatic hydrocarbons (PAH), due to methodological and practical difficulties of collecting and analysing samples from the various environmental compartments like air, water and soil and various media such as diet, cigarette smoke and workroom air. Since 1980, a large variety of novel approaches and techniques have been suggested and tested, e.g. urinary thioethers, mutagenicity in urine, levels of PAH or PAH-metabolites in blood and urine and methods for determination of adducts in DNA and proteins. Two approaches are more frequently reported: PAH-DNA-adduct monitoring in blood cells and urinary 1-hydroxypyrene monitoring. A large research effort has been made to use the extent of binding of PAH to DNA as a biomarker of exposure. The 32P-post-labeling assay detects the total of aromatic DNA-adducts and the adduct level in white blood cells is claimed to be an indicator of the biological effect of the PAH-mixture. However, the levels of aromatic DNA-adducts may be subject to appreciable analytical and biological variation. The present technical complexity of the method makes it more convenient for research applications than for routine application in occupational health practice. Pyrene is a dominant compound in the PAH mixture and is mainly metabolised to the intermediary 1-hydroxypyrene to form 1-hydroxypyrene-glucuronide, which is excreted in urine. Since the introduction of the determination of 1-hydroxypyrene in urine as a biomarker for human exposure assessment in 1985, many reports from different countries from Europe, Asia and America confirmed the potential of this novel approach. The conclusion of the first international workshop on 1-hydroxypyrene in 1993 was that urinary 1-hydroxypyrene is a solid biological exposure indicator of PAH. Studies with a comparison of several biomarkers confirmed that 1-hydroxypyrene in urine is a valid and sensitive indicator of exposure. Periodical monitoring of 1-hydroxypyrene appears to be a powerful method in controlling occupational PAH-exposure in industries. The reference level and the biological exposure limit of 1-hydroxypyrene in urine are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Minimally invasive surgery of rectal cancer: current evidence and options.
Minimally invasive surgery (MIS) of colorectal cancer has become more popular in the past two decades. Laparoscopic colectomy has been accepted as an alternative standard approach in colon cancer, with comparable oncologic outcomes and several better short-term outcomes compared to open surgery. Unlike the treatment for colon cancer, however, the minimally invasive approach in rectal cancer has not been established. In this article, we summarize the current status of MIS for rectal cancer and explore the various technical options. | {
"pile_set_name": "PubMed Abstracts"
} |
Awareness and ethical views regarding life support among doctors working in tertiary care facilities of Karachi, Pakistan.
To assess the knowledge of Life Support (LS) among doctors and to determine their ethical beliefs for the continuation or termination of Basic and Advanced Life Support services. This cross-sectional study was done from March to June 2009 that involved 110 doctors of three teaching Hospitals in Karachi (Jinnah Postgraduate Medical Centre, Aga Khan University and Ziauddin University hospitals). All the subjects were selected by random sampling and were then analysed on the basis of self-administered questionnaires. Out of the 110 doctors who took the survey, 109 (99%) had heard of Life Support. In the breakdown of doctors, 1 out of the 18 consultants (5.6%), 5 of 45 PGs (11%) and 2 out of 47 House Officers (4%) who took part in this study were unable to correctly identify the right definition of LS. Out of the total number (n = 110) of doctors, 94 (85%) said they would use Life Support in their patients and 41 (43%) of them thought life support was the only way the doctor can "do what he is supposed to do i.e. save a life", while the other reason for using LS was "Religiously, the right way". LS is still a highly sensitive subject that needs still more awareness in Karachi, Pakistan. It was surprising to find out that the knowledge of LS by residents, postgraduates and even consultants was not as high as expected. Making Basic Life Support as a part of the undergraduate course might help in clarifying the discrepancies present in the knowledge of Life Support. | {
"pile_set_name": "PubMed Abstracts"
} |
An effective strategy for the synthesis of biocompatible gold nanoparticles using danshensu antioxidant: prevention of cytotoxicity via attenuation of free radical formation.
To suppress the cytotoxicity of gold nanoparticles (AuNPs), danshensu, a naturally occurring polyphenol antioxidant isolated from Chinese herb, was used to provide a fundamental protection layer for AuNPs, to alleviate oxidative stress and as a reducing agent to react with chloroauric acid. Besides danshensu, gum arabic was chosen as an auxiliary stabilising agent to improve the stability of AuNPs against aggregation. As expected, the prepared GA-DS-AuNPs (gum arabic-danshensu-gold nanoparticle) was remarkably stable in various buffer solutions. More interestingly, the GA-DS-AuNPs not only did not show any appreciable cytotoxicity, but also could alleviate the oxidative damage induced by AuNPs. Meanwhile, the ROS/RNS scavenging activities of GA-DS-AuNPs was evaluated by electron spin resonance spectroscopy (ESR), potentiometric nitric oxide (NO) sensor and cell confocal imaging. The results suggest that GA-DS-AuNPs might have effectively reduced the AuNPs-induced cytotoxicity and oxidative stress by downregulation of ROS/NOS production. The GA-DS-AuNPs may provide potential opportunities for the application in nanomedicine and nanobiology. | {
"pile_set_name": "PubMed Abstracts"
} |
Epidermal growth factor receptor-mediated expression of NF-kappaB transcription factor in osteoblastic MC3T3-E1 cells cultured under a low-calcium environment.
We examined the effect of a low calcium environment on DNA-protein binding reaction activity of the transcription factor, NF-kappaB in osteoblastic MC3T3-E1 cells, using an electrophoretic mobility shift assay. Binding sites for the NF-kappaB sequence in DNA in nuclear protein in MC3T3-E1 cells are present. This DNA-protein binding reaction activity increased in MC3T3-E1 cells with EGF treatment, compared with those with no treatment. When MC3T3-E1 cells were placed in a low calcium environment, DNA-protein binding reaction activity seemed to decrease. This suggests that the phosphorylation of IkappaB is less active in a low calcium environment as compared with that in a normal calcium environment, because the activation of NF-kappaB is required for the dissociation of the cytoplasmic heterodimer after the phosphorylation of IkappaB. From these facts, it was suggested that gene transcription factor NF-kappaB is intimately associated with inhibitory bone formation in osteoblastic cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Nanocarrier-based topical drug delivery for an antifungal drug.
The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin. METHODS AND CHARACTERIZATIONS: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween(®) 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram. The maximum % transmittance obtained were 96.9 ± 1.0%, 95.9 ± 3.0% and 93.7 ± 1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32 ± 0.8 nm and -3.7 ± 1.2 mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89 ± 2.06 and 18.02 ± 4.3 µg/cm(2)/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37 ± 3.6 µg/cm(2) drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM). The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach. | {
"pile_set_name": "PubMed Abstracts"
} |
Primary mucinous carcinoma in a 54-year-old man.
Primary mucinous carcinoma is a rare malignant tumor that most frequently occurs in the periorbital area. This tumor originates from the deepest portion of the eccrine sweat duct. This normally asymptomatic and slow-growing tumor has demonstrated a local recurrence rate of 30% after excision with narrow surgical margins and can have local metastases. It is difficult to differentiate this tumor histologically from metastatic lesions. Immunohistochemical staining and cytokeratin profiles have been studied to aid in the differentiation between primary lesions and metastatic mucinous carcinomas. We present a case of a 54-year-old man with recurrent primary eccrine mucinous carcinoma and review the clinical, histologic, and immunohistochemical features of this tumor. | {
"pile_set_name": "PubMed Abstracts"
} |
Real time recognition of explosophorous group and explosive material using laser induced photoacoustic spectroscopy associated with novel algorithm for time and frequency domain analysis.
Energy-rich bonds such as nitrates (NO3-) and percholorates (ClO4-) have an explosive nature; they are frequently encountered in high energy materials. These bonds encompass two highly electronegative atoms competing for electrons. Common explosive materials including urea nitrate, ammonium nitrate, and ammonium percholorates were subjected to photoacoustic spectroscopy. The captured signal was processed using novel digital algorithm designed for time and frequency domain analysis. Frequency domain analysis offered not only characteristic frequencies for NO3- and ClO4- groups; but also characteristic fingerprint spectra (based on thermal, acoustical, and optical properties) for different materials. The main outcome of this study is that phase-shift domain analysis offered an outstanding signature for each explosive material, with novel discrimination between explosive and similar non-explosive material. Photoacoustic spectroscopy offered different characteristic signatures that can be employed for real time detection with stand-off capabilities. There is no two materials could have the same optical, thermal, and acoustical properties. | {
"pile_set_name": "PubMed Abstracts"
} |
L-arginine-induced hypotension in the rat: evidence that NO synthesis is not involved.
L-Arginine is the biological precursor for nitric oxide (NO). NO is formed continuously in endothelial cells and maintains a certain degree of vasodilator tone under physiological conditions. Although the formation of NO is not primarily controlled by precursor availability, the extent to which extra supplementation with L-arginine may affect endothelial NO formation, and hence, vasodilator tone and systemic blood pressure, is not entirely clear. To address this issue, we infused L-arginine i.v. in anaesthetized normotensive rats pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 50 or 200 mg-1) and in untreated controls, under continued recording of mean arterial pressure (MAP). In control animals L-arginine (25 or 100 mg kg-1 min-1) had no effect on systemic MAP (111 +/- 3 mm Hg), while L-arginine (200 mg kg-1 min-1) lowered MAP (to 70 +/- 6 mm Hg). D-Arginine (200 mg kg-1 min-1) also induced hypotension; during infusion of D-arginine MAP fell from 106 +/- 4 to 64 +/- 4 mm Hg. Pretreatment with L-NAME (50 and 200 mg kg-1) elevated MAP to 140 +/- 2 and 147 +/- 3 mm Hg, respectively, but failed to affect the hypotensive response to L-arginine; during infusion of L-arginine (200 mg kg-1 min-1) in rats pretreated with L-NAME (50 and 200 mg kg-1) MAP fell to 86 +/- 9 and 104 +/- 6 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Posterior components separation during retromuscular hernia repair.
Retromuscular ventral hernia repair with mesh is a durable technique. In this paper, we describe a novel technique which allows for significant mesh overlap via the retromuscular space in cases of massive ventral hernia. The retromuscular space is developed laterally, to the edge of the rectus sheath. The posterior rectus sheath is incised, dividing the posterior aponeurosis of the internal oblique. The dissection is carried out laterally between the internal oblique and the transversus abdominis muscle, creating space for a large mesh underlay. We have performed this technique successfully in 20 patients with a mean defect area of 223 cm(2) and a mean mesh area of 698 cm(2). Three patients developed wound complications and none complained of long-term pain or abdominal wall deformity. There has been one recurrence due to technical error after a mean 12-month follow-up. This technique of dissection between the internal oblique and transversus abdominis muscles allows for the closure of large hernia defects. The mechanism is two-fold: (1) mobility for closure of the posterior rectus sheath, dorsal to the prosthetic; and (2) increased mobility of the rectus, internal, and external obliques, allowing reconstruction of the linea alba. | {
"pile_set_name": "PubMed Abstracts"
} |
Characterization of the organic matter of sludge: determination of lipids, hydrocarbons and PAHs from road retention/infiltration ponds in France.
This paper presents the results of the organic matter characterization of sludge from two ponds (retention and infiltration) located in France. Special focus was placed on studying hydrocarbons and PAHs. This investigation is part of a global project on road and urban sludge with the aim of identifying a better means for managing these materials. Gas chromatographic and GC/MS analyses indicate that the main component of the organic fraction stems from petroleum-derived products like diesel fuel and motor oil. This finding was confirmed by the presence of biomarkers from the hopane series, as well as by pyrolytic and alkylated PAHs. Results from this study clearly show that the contaminants are mainly generated from anthropogenic petroleum sources. Due to their levels of hydrocarbon contamination, these sludge deposits must be considered as waste and cannot therefore be disposed anywhere, especially within the current context of sustainable development. | {
"pile_set_name": "PubMed Abstracts"
} |
[The use horizontal flow chromatography for the isolation of phosphatidyl inositols from various tissues].
A procedure is described which enabled to isolate rapidly at the preparative scale as well as to estimate with high rate of sensitivity the phosphatidyl inositols in mixtures of native lipids. Efficiency of the procedure developed is based on some advantages of the technique of horizontal flow chromatography as well as on use of silica gel containing potassium carbonate obtained after precipitation. Quantitative estimation of phosphatidyl inositols involved densitometry of narrow silica gel strips containing 10-15 samples simultaneously. | {
"pile_set_name": "PubMed Abstracts"
} |
[Anaphylactic shock after i.v. verapamil].
A 61-year-old woman who was being treated with verapamil because of atrial fibrillation with rapid ventricular rate, went into anaphylactic shock. Verapamil is safe and effective for treating supraventricular tachyarrhythmias and serious adverse effects are uncommon. However, hypotension, cardiogenic shock, bradycardia and precipitation or aggravation of heart failure have been described. The patient presented was successfully treated with corticosteroids and antihistaminics. | {
"pile_set_name": "PubMed Abstracts"
} |
Transient solitary pulmonary nodule caused by Dirofilaria immitis.
The second described case of solitary transient lung nodule caused by Dirofilaria immitis is reported. Diagnostic thoracotomy can be avoided with the use of enzyme-linked immunosorbent assay (ELISA), and hence a conservative serological follow-up is warranted in endemic areas. | {
"pile_set_name": "PubMed Abstracts"
} |
[A case of esophageal cancer with recurrent lymph-node metastasis successfully treated with chemo-radiotherapy after mediastinoscopy-assisted transhiatal esophagectomy].
A 63-year-old man who was diagnosed T1b esophageal cancer, for which transthoracic esophagectomy was indicated, received mediastinoscopy-assisted transhiatal esophagectomy because of the previous right thoracotomy for pulmonary tuberculosis. CT study revealed an upper mediastinal lymph-node metastasis 3 years after surgery. He was treated with chemotherapy of daily continuous 5-FU infusion (500 mg/day) and daily nedaplatin (5 mg x 5 days/week) for 4 weeks combined with concurrent radiotherapy (44 Gy). A partial response was achieved for the metastatic lymph-node lesion after chemo-radiotherapy, so boost radiotherapy (16 Gy) was given to the patient. He is still alive now without a re-growth of the lymph-node metastasis. It is important to follow-up the patient with advanced esophageal cancer carefully who received mediastinoscopy-assisted transhiatal esophagectomy. | {
"pile_set_name": "PubMed Abstracts"
} |
TLR3 and TLR7 are involved in expression of IL-23 subunits while TLR3 but not TLR7 is involved in expression of IFN-beta by Theiler's virus-infected RAW264.7 cells.
Theiler's murine encephalomyelitis virus (TMEV) infects macrophages and causes demyelinating disease (DD) in certain mouse strains. IL-23 p19/p40 and IFN-beta, which are both expressed by macrophages in response to TMEV, could contribute to or prevent DD. Because TMEV may induce macrophages' cytokines through TLR3 and TLR7 (toll-like receptors), their role in TMEV-induced IL-23 and IFN-beta expression by the RAW264.7 macrophage cell line was determined following infection with TMEV or stimulation with the poly (I:C) or loxoribine. TMEV infection or stimulation with poly (I:C), a TLR3 agonist, or loxoribine, a TLR7 agonist, induced expression of IL-23 and IFN-beta in RAW264.7 cells. In addition, TMEV infection increased expression of TLR3 and TLR7 in RAW264.7 cells. Transfection of RAW264.7 cells with shRNA plasmid vectors expressing siRNA specific for TLR3 or TLR7 concomitantly decreased expression of TLR3 or TLR7, respectively, and TMEV-induced p19 mRNA, p19 protein, and IL-23 p19/p40. Transfection with TLR7-shRNA plasmids reduced expression of TMEV-induced p40 mRNA and p40 protein. However, transfection with TLR3-shRNA plasmids increased expression of TMEV-induced p40 mRNA but decreased p40 protein. In addition, transfection with TLR3-shRNA plasmids but not TLR7-shRNA plasmids decreased expression of TMEV-induced IFN-beta mRNA. Thus TLR3 and TLR7 contribute to TMEV-induced IL-23 p19 and p40, while TLR3 contributes to TMEV-induced IFN-beta. | {
"pile_set_name": "PubMed Abstracts"
} |
Treatment of nonunion and malunion of trauma of the foot and ankle using external fixation.
Salvage of nonunion and malunion of trauma of the foot and ankle is often challenging surgery. Internal fixation provides the mainstay of most orthopedic surgeons' treatment of these conditions. Patient systemic factors, local factors, and the complex nature of these often multiplanar deformities may make external fixation a more viable option. This article provides an overview of the principles and results of the use of external fixation. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats.
To determine whether epinephrine increases lactate concentration in sepsis through hypoxia or through a particular thermogenic or metabolic pathway. Prospective, controlled experimental study in rats. Experimental laboratory in a university teaching hospital. Three groups of anesthetized, mechanically ventilated male Wistar rats received an intravenous infusion of 15 mg/kg Escherichia coli O127:B8 endotoxin. Rats were treated after 90 min by epinephrine ( n=14), norepinephrine ( n=14), or hydroxyethyl starch ( n=14). Three groups of six rats served as time-matched control groups and received saline, epinephrine, or norepinephrine from 90 to 180 degrees min. Mean arterial pressure, aortic, renal, mesenteric and femoral blood flow, arterial blood gases, lactate, pyruvate, and nitrate were measured at baseline and 90 and 180 min after endotoxin challenge. At the end of experiments biopsy samples were taken from the liver, heart, muscle, kidney, and small intestine for tissue adenine nucleotide and lactate/pyruvate measurements. Endotoxin induced a decrease in mean arterial pressure and in aortic, mesenteric, and renal blood flow. Plasmatic and tissue lactate increased with a high lactate/pyruvate (L/P) ratio. ATP decreased in liver, kidney, and heart. The ATP/ADP ratio did not change, and phosphocreatinine decreased in all organs. Epinephrine and norepinephrine increased mean arterial pressure to baseline values. Epinephrine increased aortic blood flow while renal blood low decreased with both drugs. Plasmatic lactate increased with a stable L/P ratio with epinephrine and did not change with norepinephrine compared to endotoxin values. Nevertheless epinephrine and norepinephrine when compared to endotoxin values did not change tissue L/P ratios or ATP concentration in muscle, heart, gut, or liver. In kidney both drugs decreased ATP concentration. Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypertonic Saline Injection Model of Experimental Glaucoma in Rats.
A reliable method of creating chronic elevation of intraocular pressure (IOP) in rodents is an important tool in reproducing and studying the mechanisms of optic nerve injury that occur in glaucoma. In addition, such a model could provide a valuable method for testing potential neuroprotective treatments. This paper outlines the basic methods for producing obstruction of aqueous humor outflow and IOP elevation by injecting hypertonic saline (a sclerosant) into the aqueous outflow pathway. This is one of several rodent glaucoma models in use today. In this method, a plastic ring is placed around the equator of the eye to restrict injected saline to the limbus. By inserting a small glass microneedle in an aqueous outflow vein in the episclera and injecting hypertonic saline toward the limbus, the saline is forced into Schlemm's canal and across the trabecular meshwork. The resultant inflammation and scarring of the anterior chamber angle occurs gradually, resulting in a rise in IOP after approximately 1 week. This article will describe the equipment necessary for producing this model and the steps of the technique itself. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of Maternal Gestational Hypertensive Disorders on Microvasculature in School-Age Children: The Generation R Study.
Gestational hypertensive disorders may lead to vascular changes in the offspring. We examined the associations of maternal blood pressure development and hypertensive disorders during pregnancy with microvasculature adaptations in the offspring in childhood. This study was performed as part of the Generation R Study in Rotterdam, the Netherlands (2002-2012), among 3,748 pregnant mothers and their children for whom information was available on maternal blood pressure in different periods of pregnancy and gestational hypertensive disorders. Childhood retinal arteriolar and venular calibers were assessed at the age of 6 years. We found that higher maternal systolic and diastolic blood pressures in early pregnancy were associated with childhood retinal arteriolar narrowing (P < 0.05). Higher maternal systolic blood pressure in late pregnancy, but not in middle pregnancy, was associated with childhood narrower retinal venular caliber (standard deviation score per standardized residual increase in systolic blood pressure: -0.05; 95% confidence interval: -0.08, -0.01). Paternal blood pressure was not associated with childhood retinal vessel calibers. Children of mothers with gestational hypertensive disorders tended to have narrower retinal arteriolar caliber (standard deviation score: -0.13, 95% confidence interval: -0.27, 0.01). Our results suggest that higher maternal blood pressure during pregnancy is associated with persistent microvasculature adaptations in their children. Further studies are needed to replicate these observations. | {
"pile_set_name": "PubMed Abstracts"
} |
Combination anti-gene therapy targeting c-myc and p53 in ovarian cancer cell lines.
Gene therapy clinical trials targeting p53 and other genes are underway in nongynecologic cancer systems. To explore the potential for antigene therapy in gynecologic oncology, we examined the in vitro effects of oligonucleotides targeting c-myc and p53 in the ovarian cancer cell lines CAOV-3, SKOV-3, and BG-1. The ATP cell viability assay was used to measure growth effects after 6-day treatments with 27-mer antisense phosphorothioate oligodeoxyribonucleotides (oligos) targeting the Puf/nm23 binding region of c-myc and promoter/ATG region of p53. A random sequence of the p53 27-mer was used as a control, and an untransformed fibroblast cell line was used for comparison. IC50 was defined as the oligo concentration required for 50% growth reduction compared to untreated controls. Synergistic vs antagonistic effects of oligo combinations were quantitated by combination indexes (CI) as calculated from median effect parameters by the methods of Chou and Talalay. Mean +/- SE IC50's of c-myc and p53 antisense oligos in CAOV-3 and SKOV-3 ranged from 1.0 +/- 0.2 to 9.7 +/- 1.3 microM. The IC50's of c-myc oligos were consistently lower than corresponding p53 oligos in all cell lines (P < 0.034, t test). The fibroblast cell line was sensitive to anti-c-myc and combination anti-c-myc/p53 oligos (IC50 = 1.5 +/- 0.6 and 1.4 +/- 0.2 microM, respectively), but not to anti-p53 oligos alone (IC50 > 16 microM). Nonspecific toxicity was observed at concentrations of 16 microM for all cell lines except in BG-1, where maximal growth stimulation occurred at this concentration with anti-p53 oligos. Growth stimulation was also observed in BG-1 with anti-c-myc and anti-c-myc/p53 combinations at intermediate doses, with inhibition at higher doses. While c-myc/p53 combinations in CAOV-3 were synergistic (CI < 0.8), they were antagonistic in SKOV-3 (CI > 3.2). Phosphorothioate oligos directed against c-myc and p53 in different cell lines were shown to have both antiproliferative and stimulatory activity, as single agents and in combination, at concentrations that are achievable in vivo. Because of the complex patterns of effects, further in vitro studies are warranted before considering clinical trials with these agents in gynecologic cancers. | {
"pile_set_name": "PubMed Abstracts"
} |
Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy.
Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. We investigated the dy mouse model, which has congenital muscular dystrophy due to a defect in laminin alpha 2, for evidence of cochlear dysfunction. Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate 3-month-old homozygous dy/dy and age-matched C57 control mice. The average ABR thresholds to tone-burst stimuli for four frequencies (4, 8, 16, and 32 kHz) were determined and statistically compared by ANOVA. The dy/dy mice demonstrated elevated auditory thresholds ranging from 25 to 27 dB at each frequency tested (p<0.0001). Anatomic evaluations of the ears revealed pathology ranging from extensive connective tissue infiltration within the inner ear to possible minor defects in the cells of the organ of Corti. These anatomic and physiologic observations suggest that the extracellular matrix protein laminin plays a crucial role in normal cochlear function. Furthermore, the dy congenital muscular dystrophy mouse offers a novel model for evaluation of sensorineural hearing loss associated with muscular dystrophy. | {
"pile_set_name": "PubMed Abstracts"
} |
Fivefold Symmetry and 2D Crystallization: Self-Assembly of the Buckybowl Pentaindenocorannulene on a Cu(100) Surface.
The modification of metal electrode surfaces with functional organic molecules is an important part of organic electronics. The interaction of the buckminsterfullerene fragment molecule pentaindenocorannulene with a Cu(100) surface is studied by scanning tunneling microscopy, dispersion-enabled density functional theory, and force field calculations. Experimental and theoretical methods suggest that two adjacent indeno groups become oriented parallel to the surface upon adsorption under mild distortion of the molecular frame. The binding mechanism between molecule and surface is dominated by strong electrostatic interaction owing to Pauli repulsion. Two-dimensional aggregation at room temperature leads to a single lattice structure in which all molecules are oriented unidirectionally. Their relative arrangement in the lattice suggests noncovalent intermolecular interaction through C-H⋅⋅⋅π bonding. | {
"pile_set_name": "PubMed Abstracts"
} |
QRS morphology-dependent, concordant frequency distribution of single and repetitive forms of ventricular ectopic activity.
We tested the relationship between the frequency of single premature ventricular complexes (PVCs) of specific QRS morphologies and repetitive forms (RF) of greater than or equal to 2 PVCs. Fourteen patients with multiform PVCs and RFs underwent 8-hour, two-channel continuous electrocardiographic monitoring. After a 2-hour baseline, procainamide was administered intravenously at 25 mg/min until PVC suppression or 1000 mg. Multiple regression analysis was used to relate the frequencies of repetitive forms initiated by PVCs of the most frequent QRS morphology (M1) and the second most frequent QRS morphology (M2) to the frequency of M1 and M2 single PVCs. Parallel changes in the frequency of M1 RFs and M1 PVCs occurred in 9 of 14 patients and parallel changes in the frequency of M2 RFs and M2 PVCs occurred in 7 of 14 patients (i.e., the relationships were concordant). In two patients, M1 RFs related to M2 PVC frequency; in three patients, M2 RFs related to M1 PVC frequency (i.e., the relationships were discordant). Thus concordant frequency distributions were present in 16 of 28 (57%) comparisons, while a discordant relationship occurred in only 5 of 28 (18%) comparisons (p less than 0.005). In conclusion, there is frequent concordance in the frequency distribution of single multiform PVCs and of RFs initiated by PVCs of the same QRS morphology during a pharmacologic intervention.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Bacteriologic contamination of suction tips during hip arthroplasty.
We obtained positive cultures from 12 out of 22 suction tips used in total hip arthroplasty performed in operating theaters with conventional ventilation. We recommend that the suction tubes be turned off when not in use and that the tubes be changed during operations. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression of human immunodeficiency virus (HIV) in naturally infected peripheral blood mononuclear cells: comparison of a standard co-culture technique with a newly developed microculture method.
Peripheral blood mononuclear cells (PBMCs) from 29 patients infected with human immunodeficiency virus (HIV) were cultured by two different methods. One was the standard co-culture technique, the other a newly developed microculture method. In this assay 10(6) PBMCs were cultivated in 250 microliters medium, no activating agents or allogeneic cells were present. P24 antigen production measured by this method was found in 7 out of 11 PBMC cultures of patients in the Walter Reed (WR) stage 1 or 2, whereas only 4 samples were positive by the co-culture procedure. Cultures from patients in the later stages of the disease (WR 5/6) showed a higher p24 production by the co-culture method than by the microculture assay. It is assumed that rapidly growing HIV strains can be better assessed by the co-culture method which may select for these strains. P24 expression can be more easily obtained by the microculture technique even in cases where slowly replicating strains may be present. In conclusion, results from the microculture procedure described may be a useful supplementation to findings observed by the co-culture method. | {
"pile_set_name": "PubMed Abstracts"
} |
A cost-effectiveness model to personalize antiviral therapy in naive patients with genotype 1 chronic hepatitis C.
Rapid virologic response is the best predictor of sustained virologic response with dual therapy in genotype-1 chronic hepatitis C, and its evaluation was proposed to tailor triple therapy in F0-F2 patients. Bio-mathematical modelling of viral dynamics during dual therapy has potentially higher accuracy than rapid virologic in the identification of patients who will eventually achieve sustained response. Study's objective was the cost-effectiveness analysis of a personalized therapy in naïve F0-F2 patients with chronic hepatitis C based on a bio-mathematical model (model-guided strategy) rather than on rapid virologic response (guideline-guided strategy). A deterministic bio-mathematical model of the infected cell dynamics was validated in a cohort of 135 patients treated with dual therapy. A decision-analytic economic model was then developed to compare model-guided and guideline-guided strategies in the Italian setting. The outcomes of the cost-effectiveness analysis with model-guided and guideline-guided strategy were 19.1-19.4 and 18.9-19.3 quality-adjusted-life-years. Total per-patient lifetime costs were €25,200-€26,000 with model-guided strategy and €28,800-€29,900 with guideline-guided strategy. When comparing model-guided with guideline-guided strategy the former resulted more effective and less costly. The adoption of the bio-mathematical predictive criterion has the potential to improve the cost-effectiveness of a personalized therapy for chronic hepatitis C, reserving triple therapy for those patients who really need it. | {
"pile_set_name": "PubMed Abstracts"
} |
Complications and Litigation Associated With Injectable Facial Fillers: A Cross-Sectional Study.
Soft-tissue injectable fillers are a popular treatment option for patients seeking minimally invasive facial rejuvenation. The use of soft-tissue fillers has increased significantly in the past 10 years. In 2017 alone, clinicians administered nearly 2.7 million soft-tissue fillers, up from 1.3 million in 2007. Although injectable fillers have a relatively high safety profile compared with more invasive rejuvenation procedures, serious adverse events, including intra-arterial injections, necrosis, and visual symptoms such as blindness, have been documented. Complications from injectable fillers have also been a source of litigation, which has been shown to be associated with a perceived lack of informed consent. We sought to document the reported complication rates associated with injectable facial fillers from a national database and to report on the available cases of malpractice litigation. The US Food and Drug Administration's Manufacturer and User Facility Device Experience database was used to collect the reported complications from 2013 to 2017 for the following injectable fillers: Artefill, Bellafill, Belotero, Juvederm, Radiesse, Restylane, Sculptra, and Kybella. Complications were organized by filler type, injection location, and complication type. The Thomson Reuters Westlaw Edge database was used to collect the reported jury verdicts and settlements from 2008 to 2017 for injectable facial fillers. A total of 2813 adverse events were analyzed. The most common locations for complications were the cheek (915 [32.5%]), lips (503 [17.9%]), and nasolabial fold (412 [14.6%]). The commonly reported adverse events were swelling (1,691 [60.1%]), nodule (948 [33.7%]), and pain (636 [22.6%]). Severe complications included intra-arterial injections resulting in necrosis and visual symptoms (eg, blurred vision and blindness). Forehead and dorsal nasal injections were significantly associated with intra-arterial complications resulting in necrosis and visual symptoms (P < .01). Injections with Radiesse were significantly associated with intra-arterial injections resulting in necrosis and visual symptoms (P < .01). A total of 11 malpractice cases were analyzed. The median award in the cases resolved by a verdict in favor of the plaintiff or settlement was $600,000. In 10 of the 11 cases, a lack of informed consent had been alleged. The complications associated with injectable facial fillers varied greatly, depending on factors involved with their application. The most common adverse effects were swelling, nodule formation, and pain. Serious complications stemming from intra-arterial injections included necrosis and visual disturbances, including blindness. These complications have been raised in legal cases, in which the lack of informed consent was frequently alleged. The present analysis has documented some of the potential risks involved with injectable facial fillers and demonstrated the need for a thorough informed consent process before their administration. | {
"pile_set_name": "PubMed Abstracts"
} |
A yeast protein with homology to the beta-subunit of G proteins is involved in control of heme-regulated and catabolite-repressed genes.
The product of the Saccharomyces cerevisiae AER2 gene is responsible for maintaining repression of at least two distinct regulatory pathways: heme activation/repression and catabolite repression. Mutations in the gene caused an eightfold increase in the expression of the heme-activated CYC1 gene in the absence of heme, a substantial increase in the expression of the heme-repressed ANB1 gene in the presence of heme, and a 13-fold increase in the expression of the catabolite-repressed GAL1 gene in the presence of glucose. Lesser or no increases in the expression of these genes were observed under derepressed or activation conditions. The aer2 mutations also caused a large increase in CYC7 gene expression under all conditions; this gene is subject to heme activation/repression, as well as catabolite repression. The AER2 gene was cloned and the sequence determined. The large open reading frame contiguous with the transcript from the complementing region encoded a 713-amino acid polypeptide chain with extensive homology to the beta-subunit of G proteins. The sequence revealed that AER2 is the TUP1 gene. A deletion mutation was constructed and the null phenotype was the same as the original mutants. The aer2 null mutant was shown to have increased aerobic and anaerobic levels of RNA encoding the ROX1 repressor, normally expressed only aerobically and responsible for the aerobic repression of ANB1 expression. The increase in both ROX1 and ANB1 RNAs aerobically in this mutant suggests that the repressor is nonfunctional in the mutant. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of two different methods for per-oral gastrostomy tube placement in patients with motor neuron disease (MND): PIG versus PEG procedures.
Placement of a gastrostomy tube remains the gold standard procedure to maintain nutrition in patients with motor neuron disease (MND) and bulbar muscle weakness. Percutaneous endoscopic gastrostomy (PEG) is the most commonly used procedure in this context. Per-oral image guided gastrostomy (PIG) is a new hybrid technique used successfully in non-MND patients. We have modified the PIG technique to improve patient tolerability and have undertaken a pilot evaluation of PIG compared to PEG in MND patients. Nineteen PIG and 16 PEG procedures performed over a period of four years were evaluated. Pre-procedural forced vital capacity (FVC), procedural oxygen saturation, post-procedural complications and survival duration were recorded. Results showed that a gastrostomy tube was successfully placed in 95% of the PIG group and 80% of the PEG group. Rates of minor complications were comparable in both groups (21% in PIG, 23% in PEG). No life-threatening complications occurred in either group. Procedural mean oxygen saturations were higher in the PIG group compared to the PEG group (p < 0.001). No significant survival differences were observed. This study provides evidence for the use of the PIG procedure as a safe and well tolerated alternative to PEG in MND patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Effectiveness and safety of carotid artery stenting for significant carotid stenosis in patients with contralateral occlusion (from the German ALKK-CAS Registry experience).
Data on the safety of carotid artery stenting (CAS) in a large number of unselected patients with contralateral occlusion and significant ipsilateral stenosis are less known. Accordingly, we evaluated 3,137 patients undergoing CAS who were enrolled in a German Registry from 2000 to 2008 and compared the clinical features and in-hospital outcomes of those with and without contralateral carotid occlusion. Contralateral carotid occlusion was present in 191 patients (6.1%) undergoing CAS. Despite the similar age of the patients with and without contralateral carotid occlusion, those with contralateral occlusion had a greater prevalence of co-morbidities, complex carotid stenosis, and greater number of focal neurologic lesions on the contralateral side. The incidence of in-hospital events, including death (1.0% vs 0.5%), ipsilateral major stroke (1.1% vs 1.1%), death or major ipsilateral stroke (1.6% vs 1.4%), ipsilateral transient ischemic attack (2.7% vs 2.5%), myocardial infarction (0.0% vs 0.1%), and reintervention (0.5% vs 1.1%), was low and was not significantly different between those with and without contralateral occlusion (p >0.05 for all comparisons). Among patients with carotid occlusion, major ipsilateral stroke (2.2%), death (2.2%), and a combination of these 2 events (3.3%) were observed exclusively in symptomatic patients with no event in asymptomatic patients. In conclusion, our data from a large number of patients undergoing CAS in a recent contemporary community-based practice attests to the low risk of periprocedural events among patients with contralateral carotid occlusion supporting CAS as an attractive option for the treatment of these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Urinary leukocyte esterase screening for asymptomatic sexually transmitted disease in adolescent males.
The objective of this study was to evaluate the effectiveness of urinary leukocyte esterase on random urine specimens as a screening test for chlamydial and gonococcal urethral infections in asymptomatic males. Random urine specimens were obtained on 106 consecutive asymptomatic adolescent males during intake physical examination at a residential vocational training program. Results of urinary leukocyte esterase were compared to those of urethral cultures for Chlamydia trachomatis and Neisseria gonorrhoeae. Five subjects had positive chlamydia cultures, three subjects had positive gonococcal cultures, and one patient had positive cultures for both organisms. Sixteen subjects had leukocyte esterase tests reported as "trace" or greater. When compare to positive culture results for either Chlamydia or gonorrhea, urinary leukocyte esterase activity had a sensitivity of 78%, specificity of 91%, and positive predictive value of 44%. A random urine specimen for urinary leukocyte esterase activity is a cost-effective screening method for chlamydial and gonococcal urethral infections in asymptomatic adolescent males. | {
"pile_set_name": "PubMed Abstracts"
} |
Cancer-associated IDH mutations: biomarker and therapeutic opportunities.
The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology. The nature of the heterozygous, point mutations mapping to arginine residues involved in the substrate binding inspired several research teams to investigate their impact on the biochemical activity of these enzymes. Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to α-ketoglutarate (αKG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of αKG to the metabolite D2-hydroxyglutarate (D-2HG). Across glioma as well as several hematologic malignancies, mutations in IDH1 and IDH2 have shown prognostic value. Several hypotheses implicating the elevated levels of D-2HG and tumorigenesis, and the therapeutic potential of targeting mutant IDH enzymes will be discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
R(+)-methanandamide-induced apoptosis of human cervical carcinoma cells involves a cyclooxygenase-2-dependent pathway.
Cannabinoids have received renewed interest due to their antitumorigenic effects. Using human cervical carcinoma cells (HeLa), this study investigates the role of cyclooxygenase-2 (COX-2) in apoptosis elicited by the endocannabinoid analog R(+)-methanandamide (MA). COX-2 expression was assessed by RT-PCR and Western blotting. PGE2/PGD2 levels in cell culture supernatants and DNA fragmentation were measured by ELISA. MA led to an induction of COX-2 expression, PGD2 and PGE2 synthesis. Cells were significantly less sensitive to MA-induced apoptosis when COX-2 was suppressed by siRNA or the selective COX-2 inhibitor NS-398. COX-2 expression and apoptosis by MA was also prevented by the ceramide synthase inhibitor fumonisin B1, but not by antagonists to cannabinoid receptors and TRPV1. In line with the established role of peroxisome proliferator-activated receptor gamma (PPARgamma) in the proapoptotic action of PGs of the D and J series, inhibition of MA-induced apoptosis was also achieved by siRNA targeting lipocalin-type PGD synthase (L-PGDS) or PPARgamma. A role of COX-2 and PPARgamma in MA-induced apoptosis was confirmed in another human cervical cancer cell line (C33A) and in human lung carcinoma cells (A549). This study demonstrates COX-2 induction and synthesis of L-PGDS-derived, PPARgamma-activating PGs as a possible mechanism of apoptosis by MA. | {
"pile_set_name": "PubMed Abstracts"
} |
Estimating seroprevalence of vaccine-preventable infections: is it worth standardizing the serological outcomes to adjust for different assays and laboratories?
The aim of the European Sero-Epidemiology Network 2 (ESEN2) project was to estimate age-specific seroprevalence for a number of vaccine-preventable diseases in Europe. To achieve this serosurveys were collected by 22 national laboratories. To adjust for a variety of laboratory methods and assays, all quantitative results were transformed to a reference laboratory's units and were then classified as positive or negative to obtain age-specific seroprevalence. The aim of this study was to assess the value of standardization by comparing the crude and standardized seroprevalence estimates. Seroprevalence was estimated for measles, mumps, rubella, diphtheria, varicella zoster and hepatitis A virus (HAV) and compared before and after serological results had been standardized. The results showed that if no such adjustment had taken place, seroprevalence would have differed by an average of 3·2% (95% bootstrap interval 2·9-3·6) although this percentage varied substantially by antigen. These differences were as high as 16% for some serosurveys (HAV) which means that standardization could have a considerable impact on seroprevalence estimates and should be considered when comparing serosurveys performed in different laboratories using different assay methods. | {
"pile_set_name": "PubMed Abstracts"
} |
Distribution of microtubules in prolactin cells of lactating rats.
The intracellular distribution of microtubules was studied using serial sections of prolactin cells in anterior pituitary glands from lactating rats. Numerous microtubules were present in these cells following fixation with glutaraldehyde and osmium tetroxide. The greatest number of microtubules were present in the Golgi complex, situated around the perimeter and in association with the cisternae, vesicles and developing secretory granules. Microtubules were found in channels between groups of parallel cisternae of rough surfaced endoplasmic reticulum and in close proximity to small vesicles. They were also located adjacent to mitochondria, the plasmalemma, the nuclear envelope, and among mature secretory granules. Due to their orientation within the cell, it is suggested that the microtubules may act to direct the movement of organelles from one region of the cell to another and to give internal support to the cell. | {
"pile_set_name": "PubMed Abstracts"
} |
Modifying the N-terminus of polyamides: PyImPyIm has improved sequence specificity over f-ImPyIm.
Seven N-terminus modified derivatives of a previously published minor-groove binding polyamide (f-ImPyIm, 1) were synthesized and the biochemical and biophysical chemistry evaluated. These compounds were synthesized with the aim of attaining a higher level of sequence selectivity over f-ImPyIm (1), a previously published strong minor-groove binder. Two compounds possessing a furan or a benzofuran moiety at the N-terminus showed a footprint of 0.5microM at the cognate ACGCGT site (determined by DNase I footprinting); however, the specificity of these compounds was not improved. In contrast, PyImPyIm (4) produced a footprint of 0.5microM but showed a superior specificity using the same technique. When evaluated by thermal melting experiments and circular dichroism using ACGCGT and the non-cognate AAATTT sequence, all compounds were shown to bind in the minor-groove of DNA and stabilize the cognate sequence much better than the non-cognate (except for the non-amido-compound that did not bind either sequence, as expected). PyImPyIm (4) was interesting as the DeltaT(m) for this compound was only 4 degrees C but the footprint was very selective. No binding was observed for this compound with a third DNA (non-cognate, ACCGGT). ITC studies on compound 4 showed exothermic binding with ACGCGT and no heat change was observed for titrating the compound to the other two DNA sequences. The heat capacity (DeltaC(p)) of the PIPI/ACGCGT complex calculated from the hydrophobic interactions and SASA calculations was comparable to the experimental value obtained from ITC (-146calmol(-1)K(-1)). SPR results provided confirmation of the sequence specificity of PyImPyIm (4), with a K(eq) value determined to be 7.1x10(6) M(-1) for the cognate sequence and no observable binding to AAATTT and ACCGGT. Molecular dynamic simulations affirmed that PyImPyIm (4) binds as a dimer in an overlapped conformation, and it fits snugly in the minor-groove of the ACGCGT oligonucleotide. PyImPyIm (4) is an especially interesting molecule, because although the binding affinity is slightly reduced, the specificity with respect to f-ImPyIm (1) is significantly improved. | {
"pile_set_name": "PubMed Abstracts"
} |
The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.
This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhythmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input. | {
"pile_set_name": "PubMed Abstracts"
} |
[Infectious respiratory complications of AIDS].
Respiratory infections are particularly frequent in HIV infection. They depend upon the degree of immunodeficiency, the geographical region and a possible prophylaxis. Bronchopneumopathies caused by pyogenic organisms (notably pneumococci) appear when the number of T4 lymphocytes is little reduced. Pulmonary tuberculosis, particularly frequent in Africans and Haitians, occurs in patients with moderate immunodeficiency (T4 between 200 and 300/mm3). HIV infections modify the epidemiology of tuberculosis in Africa, but also in the USA and probably in Europe. Despite a well-established prophylaxis, pneumocystosis, which develops when the number of T4 cells falls below 200/mm3, is the opportunistic pathology which in most cases points to AIDS in the USA and in France. Atypical mycobacterial infections (Mycobacterium avium complex) and CMV infections occur at a late stage of the disease in patients with severe immunodeficiency. Noticeable advances have recently been made in the treatment of these complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Are fusion inhibitors active against all HIV variants?
Genetic sequence alignment of the transmembrane region from HIV-1 group O and HIV-2 isolates was performed to examine their potential susceptibility to fusion inhibitors enfuvirtide (T-20) and T-1249. A high genetic diversity within the HRI and HR2 domains was found, which should compromise any antiviral effect of T-20 on HIV-2 and HIV-1 group O viruses. However, conserved sequences in the gp41 regions from HIV-1 group O involved in T-1249 susceptibility might result in a much broader antiviral effect of T-1249 on HIV-1 variants. In contrast, genetic diversity in those regions make unlikely any activity of these compounds on HIV-2. | {
"pile_set_name": "PubMed Abstracts"
} |
[Anti-acetylcholine receptor antibodies: effect of immunosuppressive drug therapy in patients with myasthenia gravis].
We studied anti-acetylcholine receptor antibodies (ARAb) in 25 patients with myasthenia gravis before and after the immunosuppressive drug (steroid) therapy and in 22 patients before and after thymectomy. The clinical effect after the treatment was correlated with the reduction of ARAb levels by more than 20% in 62% of patients. The ARAb levels did not change, or even increased, in 15% patients despite the improvement of their clinical state. We showed the direct correlation between the clinical improvement and the decrease of ARAb level. | {
"pile_set_name": "PubMed Abstracts"
} |
The Association of Socioeconomic Conditions and Readiness to Learn New Ways of Performing Daily Activities in Older Adults With Functional Difficulties.
Behavioral interventions for older adults can reduce difficulties in performing daily activities, hospitalizations, and mortality risk. The success of behavior change interventions, however, can be affected by a participant's readiness to adopt changes. This study evaluates whether socioeconomic conditions, particularly financial strain affording food, are associated with readiness to change. We conducted a cross-sectional, descriptive study of baseline data from disabled older adults ( N = 147) participating in an intervention to reduce physical disability. Readiness to change score was rated at the start of the intervention by interventionists as either pre-action (precontemplation = 1, contemplation = 2, preparation = 3) or action (=4). Participants reporting high financial strain affording food were more likely to have high readiness at the start of intervention; the association of this specific socioeconomic condition with readiness may be an important consideration in implementing interventions to reduce disability. | {
"pile_set_name": "PubMed Abstracts"
} |
Enhanced intracoronary thrombolysis with urokinase using a novel, local drug delivery system. In vitro, in vivo, and clinical studies.
Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device. THe Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with 123I-labeled urokinase that was administered either by the Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150,000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient. Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site. | {
"pile_set_name": "PubMed Abstracts"
} |
Granulomatous inflammation masquerading as an infected urachal cyst.
Errors in urachal obliteration may result in 4 clinical anomalies: patent urachus, urachal cyst, urachal sinus, or vesicourachal diverticulum. Despite the fact that urachal cysts are one of the more common of these anomalies, most go undetected, presenting in the setting of infection. There are reports in the literature of cysts misdiagnosed as other inflammatory processes; however, the converse is reported with less frequency. We present the case of a 3-year-old girl who was admitted to our institution with a suspected urachal cyst. This was subsequently diagnosed as a granulomatous mass caused by the gram negative bacterium Bartonella. | {
"pile_set_name": "PubMed Abstracts"
} |
Subtyping of Magnetically Isolated Breast Cancer Cells Using Magnetic Force Microscopy.
Circulating tumor cell (CTC) which recently arisen as potential sources for monitoring and characterizing non-haematologic cancers and their metastatic derivatives. Immunomagnetic microbeads and magnetic nanoparticles (MNPs) have been extensively explored to isolate CTCs from blood samples. However, MNPs attached on the membrane protein are interrupted further analysis to distinguish the cancer subtype by consumption or blocking the target surface marker. Here, an MNP-mediated analysis method for surface marker expression profile by magnetic force microscopy (MFM) is described. Two MNPs, zinc ferrite and iron oxide, are showed distinct phase shift (-16.5° and -3.7°, respectively) signal on the MFM images. The antibody conjugated MNPs are successfully isolated target cells without giving damage to the cell. The MFM image of MNP decorated cells show clear differences between two breast cancer cell lines, MCF-7 and SK-BR-3, which proof the cancer subtyping property using MFM method. To confirmation of the surface marker consumption during the cell isolation, antibody-conjugated quantum dots and drug-loaded oleosome are treated on the cells, thereby MNP decorated cells are survived. This newly developed MFM analysis method provides a new direction to utilize the MNP for the surface marker expression phenotypes. | {
"pile_set_name": "PubMed Abstracts"
} |
[Angiocardioscintigraphy in the cardiological surveillance of chemotherapy with anthracyclines].
Equilibrium angiocardioscintigraphy is a noninvasive nuclear medical method which allows cardiac function to be assessed. It is widely used in oncology since some clinically important drugs used in antitumor chemotherapy have a marked cardiotoxic effect. Angiocardioscintigraphy enables several parameters characteristic of cardiac function to be assessed, namely the left ventricular ejection fraction whose alterations during chemotherapy allow possible cardiotoxic side effects to be revealed before the development of irreversible heart failure. | {
"pile_set_name": "PubMed Abstracts"
} |
Artificial intelligence based approaches to evaluate actual evapotranspiration in wetlands.
Wetlands are extraordinary ecosystems and important climate regulators that also contribute to reduce natural disaster risk. Unfortunately, wetlands are declining much faster than forests. The safeguarding of the wetlands also needs knowledge of the dynamics that control the water balance of these environments. Therefore, an accurate estimation of evapotranspiration in wetlands is an essential task. When adequate experimental data are available, some algorithms deriving from Artificial Intelligence research represent a promising alternative to the most common estimation techniques. In this study, starting from daily measurements of climatic variables such as net solar radiation, depth to water, wind speed, mean relative humidity, maximum temperature, minimum temperature, and mean temperature, using the Random Forest, Additive Regression of Decision Stump, Multilayer Perceptron and k-Nearest Neighbors algorithms, 24 estimation models, different in input variables, have been developed and compared. The data have been provided by USGS. They have been obtained from a measuring site in wetlands of Indian River County, Florida using the eddy-covariance technique. The accuracy of these models based on AI algorithms remains good even if the number of input variables is reduced from 7 to 3. Net solar radiation, mean temperature and mean relative humidity or wind speed measurements allow obtaining a sufficiently accurate estimation model. Random Forest and k-Nearest Neighbors provide slightly better performance than Additive Regression of Decision Stump and Multilayer Perceptron. The analyzed models show in most cases the lowest accuracy in the range 2-4 mm/day, while the highest accuracy is obtained in the ranges 0-2 mm/day and 6-8 mm/day, with the exception of the models based on the Additive Regression, which show similar levels of accuracy in the different considered sub-intervals. | {
"pile_set_name": "PubMed Abstracts"
} |
Association of elevated levels of prothrombin fragment 1+2 and Arg506 to Gln mutation in patients with a history of ischemic stroke.
Recent findings have indicated the association between APC-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from stroke. Therefore, we studied APC-resistance in 50 young adults (< or =45 yrs) with a history of ischemic stroke. Eleven out of fifty cerebrovascular subjects showed APC-resistance, while 2 had PC deficiency and 3 PS deficiency. No deficiencies in the anticoagulant protein AT III and in fibrinolytic proteins were found. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hypercoagulable states, was also measured in patients and family members of resistant subjects (n = 38). DNA analysis showed factor V R506Q mutation (Leiden mutation) in 11 patients and their relatives with poor response to activated protein C detected by APTT tests. Of 11 investigated subjects with APC-resistance, 9 were heterozygotes and 2, with the lowest APC-ratio values, were homozygotes for factor V mutation. Among 38 relatives, 22 showed a poor response to APC and according to the APC-ratio values, 18 were heterozygotes and 4 homozygotes for FV Leiden mutation. The mutation, in heterozygous form, was also found in 2% of our normal population (n = 100). The plasma concentration of F1+2 was significantly higher both in 11 individuals carrying the FV:Q506 mutation and in 39 patients without APC-resistance compared to that found in the control group. However, the patients with FV:Q506 mutation showed the highest values in F1+2. In the studied family members F1+2 plasma levels were within normal values. Our findings indicate a possible involvement of APC-resistance in the pathogenesis of cerebral thrombosis in young adults and agree with the hypothesis that individuals with APC-resistance have an imbalance between pro-and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state. | {
"pile_set_name": "PubMed Abstracts"
} |
No-nonsense functions for long noncoding RNAs.
The mysterious secrets of long noncoding RNAs, often referred to as the Dark Matter of the genome, are gradually coming to light. Several recent papers dig deep to reveal surprisingly complex and diverse functions of these enigmatic molecules. | {
"pile_set_name": "PubMed Abstracts"
} |
Multiple memory systems and consciousness.
This Introduction to the Special Issue on Human Memory discusses some of the recent and current developments in the study of human memory from the neuropsychological perspective. A problem of considerable current interest, that of multiple memory systems, is a problem in classification. Much of the evidence for it is derived from clinical and experimental observations of dissociations between performances in memory tasks. The distinction between short-term and long-term memory is considered as an example of classification by dissociation. Current conceptualizations of multiple long-term memory systems are reviewed from the vantage point that distinguishes among three major kinds of memory--episodic, semantic, and procedural. These systems are briefly described and compared, and current views concerning the relation between them are discussed. The role of consciousness in memory is raised against the backdrop of the suggestion that it may be necessary to differentiate among several kinds of consciousness. | {
"pile_set_name": "PubMed Abstracts"
} |
Newborn transition.
The transition from intrauterine to extrauterine life is a complex adaptation. Although, in a sense, the entire time in utero is in preparation for this transition, there are many specific anatomic and physiologic changes that take place in the weeks and days leading up to labor that facilitate a healthy transition. Some, including increasing pulmonary vasculature and blood flow, are part of an ongoing process of maturation. Others, such as a reversal in the lung from secreting fluid to absorbing fluid and the secretion of pulmonary surfactant, are associated with the hormonal milieu that occurs when spontaneous labor is impending. Interventions such as elective cesarean birth or induction of labor may interfere with this preparation for birth. Postnatal interventions such as immediate clamping of the umbilical cord and oropharyngeal suction may also compromise the normal process of newborn transition. This article reviews the physiology of the fetal to newborn transition and explores interventions that may facilitate or hinder the optimal process. | {
"pile_set_name": "PubMed Abstracts"
} |
[Fluorescein photography with polaroid film (author's transl)].
There are no difficulties in performing documentation of fluorescein pictures by slit lamp polaroid photography. This suitable method is recommended for control of corneal lesions in fitting contact lenses, and in special cases of fluorescein angiography. | {
"pile_set_name": "PubMed Abstracts"
} |
Specificity and editing by apoptosis of virus-induced cytotoxic T lymphocytes.
Recent studies have defined an immunological network by which the acute cytotoxic T-lymphocyte response to viral infection modulates or is modulated by the antigen load and by crossreactive memory T cells. Down regulation of the acute CTL response can be associated with either antigen-dependent or antigen-independent apoptosis, and the host enters a state of immune deficiency as these T cells become sensitized to apoptotic mechanisms. | {
"pile_set_name": "PubMed Abstracts"
} |
Calcitonin.
Calcitonin operates predominantly to regulate acute hypercalcemic states. The response to calcium challenges is lowest in elderly women; however, the contribution of calcitonin to the etiology of osteoporosis is unclear. The calcitonin receptor is a member of a supergene family consisting of G-protein-linked receptors with seven domains spanning the cellular membrane. These receptors are distributed in calcium-responsive tissues, gut, and hypothalamus and mediate calcitonin's known clinical effects of hypocalcemia, enhanced gastric motility, and analgesia. Therapeutic use of calcitonin is indicated in both perimenopausal and postmenopausal women with contraindications or intolerance to estrogen replacement therapy, Paget's disease, painful vertebral compression fractures, and steroid-induced osteopenia. | {
"pile_set_name": "PubMed Abstracts"
} |
New members in the Ni(n+1)(QO3)nX2 family: unusual 3D network based on Ni4ClO3 cubane-like clusters in Ni7(TeO3)6Cl2.
Three new members in the family of nickel(II) tellurium(IV)/selenium(IV) oxyhalides generally formulated as Ni(n+1)(QO3)nX2 (Q = Te, X = Cl, n = 6, 10; Q = Se, X = Br, n = 4) have been synthesized by solid-state reactions of NiX2, QO2, and NiO (or Ni2O3) at high temperature. The structure of Ni7(TeO3)6Cl2 features a novel 3D network based on Ni4ClO3 cubane-like clusters with Te atoms located at the cavities of the network. Ni4ClO3 clusters are interconnected into a hexagonal layer through additional O...O edges. The neighboring two layers are further interconnected, via sharing of common Ni(II) atoms, into a novel 3D network. The 3D open framework of Ni5(SeO3)4Br2 is built from 2D nickel(II) oxybromide layers bridged by Se and additional Ni atoms. The structure of Ni11(TeO3)10Cl2 features a condensed 3D network based on NiO5Cl, NiO6, and NiO5 polyhedra interconnected via corner and edge sharing, as well as O-Te-O bridges. The results of magnetic property measurements indicate that all three compounds display antiferromagnetic interactions between nickel(II) centers. | {
"pile_set_name": "PubMed Abstracts"
} |
Post-transfusion purpura responding to high dose intravenous IgG: further observations on pathogenesis.
A typical case of post-transfusion purpura (PTP) is described in a 61-year-old woman. Treatment with steroids corrected the purpuric manifestations, but the patient remained thrombocytopenic in spite of steroid therapy and plasma exchange. However, an intravenous infusion of high dose IgG led to a rapid and sustained increase in the platelet count. The mechanism of thrombocytopenia in PTP is still a matter for speculation, as the platelet specific antibody usually cannot be shown to react with the patient's own platelets in vitro. Therefore, the finding of a coexistent platelet specific IgM autoantibody in this patient, first detected during the early recovery phase, is of particular interest and suggests a possible autoimmune basis for the profound thrombocytopenia. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of Cu and Ni on growth, mineral uptake, photosynthesis and enzyme activities of Chlorella vulgaris at different pH values.
A pH dependent reduction in growth, pigment, ATP content, O2- evolution, carbon fixation, photosynthetic electron transport system, nutrient uptake (NO3- and NH4+), nitrate reductase, and ATPase activities and increase in K+ efflux of Chlorella vulgaris was noticed following supplementation of Cu and Ni to the culture medium. PS II was found to be more sensitive to both pH and metals than PS I. Though, nitrate reductase (NR) was more sensitive to both pH and metals, the ATPase was however, more sensitive to metals but less sensitive to acidic pH. Acid pH was found to inhibit the nutrient (NO3- and NH4+) uptake and nitrate reductase in a non-competitive manner. The inhibition produced by the test metals alone was of non-competitive type for NO3- uptake, nitrate reductase and ATPase and competitive for NH4+ uptake. Acidity not only inhibited the metabolic variables directly but also through facilitated uptake of metals and increased membrane permeability. A very low sensitivity of ATPase to acidic pH seems to be responsible for the survival of algae in acid environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation and functional analysis of mitochondria from the nematode Caenorhabditis elegans.
Mitochondria are essential organelles with central roles in diverse cellular processes such as apoptosis, energy production via oxidative phosphorylation, ion homeostasis, and the synthesis of heme, lipid, amino acids, and iron-sulfur clusters. Defects in the mitochondrial respiratory chain lead to or are associated with a wide variety of diseases in humans. The nematode Caenorhabditis elegans provides a powerful genetic and developmental model system for reproducing deleterious mutations causing mitochondrial dysfunction and investigating their metabolic consequences and their mechanisms of pathology. In this chapter, we describe the growth of C. elegans in liquid culture, the isolation of crude and purified mitochondria, and polarographic and histochemical approaches for measuring mitochondrial respiratory chain function. | {
"pile_set_name": "PubMed Abstracts"
} |
[Possibilities and limitations of medicinal teas].
| {
"pile_set_name": "PubMed Abstracts"
} |
Production of avirulent mutants of Mycobacterium bovis with vaccine properties by the use of illegitimate recombination and screening of stationary-phase cultures.
A better tuberculosis vaccine is urgently required to control the continuing epidemic. Molecular techniques are now available to produce a better live vaccine than BCG by producing avirulent strains of the Mycobacterium tuberculosis complex with known gene deletions. In this study, 1000 illegitimate recombinants of Mycobacterium bovis were produced by illegitimate recombination with fragments of mycobacterial DNA containing a kanamycin resistance gene. Eight recombinant strains were selected on the basis of their inability to grow when stationary-phase cultures were inoculated into minimal medium. Five of these recombinants were found to be avirulent when inoculated into guinea pigs. Two of the avirulent recombinants produced vaccine efficacy comparable to BCG against an aerosol challenge in guinea pigs with M. bovis. One of these recombinants had an inactivated glnA2 gene encoding a putative glutamine synthetase. Transcriptional analysis showed that inactivation of glnA2 did not affect expression of the downstream glnE gene. The other recombinant had a block of 12 genes deleted, including the sigma factor gene sigG. Two avirulent recombinants with an inactivated pckA gene, encoding phosphoenolpyruvate carboxykinase which catalyses the first step of gluconeogenesis, induced poor protection against tuberculosis. It is clear that live avirulent strains of the M. tuberculosis complex vary widely in their ability as vaccines to protect against tuberculosis. Improved models may be required to more clearly determine the difference in protective effect between BCG and potential new tuberculosis vaccines. | {
"pile_set_name": "PubMed Abstracts"
} |
[Treatment of colorectal cancer--hepatic metastases].
The aim of this study was to evaluate the effect of the local therapy for colorectal liver metastases on overall survival. Seventy-two patients who had resected liver metastases from colorectal cancer during the period from 1982 to 2001 were evaluated for survival. There was no significant difference in overall survival by either surgical method for colorectal liver metastases or postoperative arterial infusion chemotherapy. However, the 5-year survival rate of resected metachronous liver metastases with postoperative arterial infusion chemotherapy was 44.9%, and that for patients with no extra hepatic metastases was 57.4%. Patients who have metachronous liver metastases from colorectal cancer should therefore be considered for postoperative arterial infusion chemotherapy. It is necessary to improve the outcome for cases that have extra hepatic metastases. | {
"pile_set_name": "PubMed Abstracts"
} |
An evaluation of behavioral health compliance and microbial risk factors on student populations within a high-density campus.
The aim of this Canadian study was to assess student behavioral response to disease transmission risk, while identifying high microbial deposition/transmission sites. A student survey was conducted during October 2009. The methods included a survey of students to assess use of health services, vaccination compliance, and hygiene along with a microbial analysis of potential transmission sites targeting specific residence buildings on campus. Results indicated that most students maintained that they were worried about H1N1 and reported making changes in hygienic behavior, with the majority not planning to be vaccinated. The microbial analysis indicated contamination of fomites in co-ed residences to be higher than either male or female student residences. A consideration of physical space along with behavioral factors is required in order to properly assess risk pathways in the establishment of an evidence-based infection control plan for universities and their contiguous communities. | {
"pile_set_name": "PubMed Abstracts"
} |
Scanning nonlinear dielectric potentiometry.
Measuring spontaneous polarization and permanent dipoles on surfaces and interfaces on the nanoscale is difficult because the induced electrostatic fields and potentials are often influenced by other phenomena such as the existence of monopole fixed charges, screening charges, and contact potential differences. A method based on tip-sample capacitance detection and bias feedback is proposed which is only sensitive to polarization- or dipole-induced potentials, unlike Kelvin probe force microscopy. The feasibility of this method was demonstrated by simultaneously measuring topography and polarization-induced potentials on a reconstructed Si(111)-(7 × 7) surface with atomic resolution. | {
"pile_set_name": "PubMed Abstracts"
} |
Metabolic control analysis to identify optimal drug targets.
This chapter describes the basic principles of Metabolic Control Analysis (MCA) which is a quantitative methodology to evaluate the importance and relative contribution of individual metabolic steps in the overall functioning of a particular system. The control on the flux through a metabolic pathway or subsystem can be quantified by the control coefficients of the individual enzymes or components which reflects the extent to which the component is rate-limiting. The perturbation of an individual step is measured by its elasticity coefficient. The effect of perturbation of a single step on the entire pathway or subsystem is, in turn, measured by the response coefficient. Differential control analysis can be used to compare flux through a single metabolic pathway in a pathogen with the same pathway in its host to identify uniquely vulnerable steps with the greatest potential for specifically inhibiting flux through the pathogen metabolic pathway. The utility of this methodology is illustrated with the glycolysis in Trypanosomes and with oncogenic signaling. | {
"pile_set_name": "PubMed Abstracts"
} |
Hybrid POSS-containing brush on gold surfaces for protein resistance.
A hybrid polymer brush containing poly(ethylene glycol) (PEG) chains and polyhedral oligosilsesquioxane (POSS) on a gold surface is presented that exhibits an excellent protein resistance and long-term stability. A series of hybrid polymer brushes with different length and numbers of PEG chains are fabricated through chemisorption of PEG-POSS-SH on the gold surface. Protein adsorption of these hybrid brushes is investigated. The amount of protein adsorption decreases with increasing lengths and numbers of PEG chains. After immersion in BSA solution for two months, the PPS4 brushes retain their protein resistance, while a PEG-SH layer loses its non-fouling performance. These POSS-containing hybrid polymer brushes might offer an alternative for modification of gold surface with an excellent protein resistance for long-term applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Antioxidant activity of reduced menadione in solvent solution and in model membranes.
The antioxidant activity of reduced menadione was investigated and compared with that of alpha-tocopherol both in solvent solution and in large unilamellar vesicles by using azocompounds as free radical generators. The results show that: i) reduced menadione behaves as a chain-breaking antioxidant; ii) its inhibition rate constant is similar to that of alpha-tocopherol in homogeneous solution, whereas it is 4 times larger in egg yolk lecithin vesicles; iii) the stoichiometric factor is found lower than 1 in both systems, since a substantial portion of menadiol is consumed by autoxidation and does not contribute to radical trapping; iv) when both alpha-tocopherol and menadiol are present in vesicles, reduced menadione can spare alpha-tocopherol. Data presented here suggest that the reduced form of vitamin K may protect, when present, cellular membranes from free radical damage. | {
"pile_set_name": "PubMed Abstracts"
} |
Technical aspects of unilateral dual kidney transplantation from expanded criteria donors: experience of 100 patients.
One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety-five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end-to-side. Surgical complications were comparable in both groups. At 3-year follow-up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3-years follow-up. | {
"pile_set_name": "PubMed Abstracts"
} |
Alteration and recovery of bleeding times, platelet aggregation and fatty acid composition of individual phospholipids in platelets of human subjects receiving a supplement of cod-liver oil.
The effect of supplementation with cod-liver oil containing eicosapentaenoic acid (EPA), 20:5 omega 3, on bleeding times, thrombin-induced platelet aggregation, platelet protein, platelet cholesterol, and the level and fatty acid composition of individual phospholipids in the platelets of human subjects was determined. Measurement of these parameters was conducted before the subjects received the supplement (day 0), after they received the supplement for 14 days (day 14), and 14 days after the supplement was terminated (day 28) so as to monitor recovery. The mean bleeding times exhibited a marked increase (by 81%) with supplementation and returned to near basal (day 0) values within 14 days after the supplement was terminated. Cod-liver oil supplementation significantly reduced thrombin-induced platelet aggregation with a partial recovery being exhibited by day 28. The content of phospholipid, cholesterol and protein (microgram/10(9) platelets) was not significantly different (P greater than 0.05) when isolated from the subjects at day 0, 14 and 28, as neither were the composition of individual phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and sphingomyelin (SPH)] given as % of total phospholipid. However, the fatty acid compositions of all platelet phospholipids were altered significantly by the fish oil supplement. In PC, EPA rose from 0.3 to 2.9% of total fatty acids and docosahexaenoate from 0.7 to 1.8% concomitant with a drop in arachidonate (from 14.1 to 9.6%) and linoleate (from 10.2 to 7.9%); these levels approached basal levels 14 days after supplementation was terminated.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
One-step electrochemical fabrication of nanoporous gold wire arrays from ionic liquid.
Nanoporous gold wire arrays were fabricated by a simple and straightforward template-free method from ionic liquid. The electrodeposition of AuZn nanowires was coupled with the galvanic metal displacement of the zinc in the wires by gold, creating the final nanoporous gold wire arrays. | {
"pile_set_name": "PubMed Abstracts"
} |
[Outcome at two years corrected age of a cohort of very low birth weight infants from hospitals within the neonatal SEN1500 network].
To describe growth and neurodevelopmental status of 4,944 children who completed a follow-up at two years of corrected age out of the 10,456 newborns with weight ≤1500g born between the years 2002-2007 and discharged from hospitals within the network SEN1500. A total of 522 newborns were excluded as they had some type of malformation. The total number of children assessed represents the 49.76% of children discharged alive and without malformations. A retrospective review was conducted using prospectively collected data in the SEN1500 database. We compared growth data at two years of corrected age according to birth weight and sex. Motor impairment, incidence of cerebral palsy, visual and hearing disabilities, and abnormal neurodevelopment for gestational age were analysed between groups. We studied the associations between cerebral palsy (CP) and perinatal factors. At 2 years of age 44.2% of children had a weight <2 SD for corrected age. Children with birth weight ≤1000g showed worse outcomes in growth. Some type of motor impairment was observed in 6.96% of the infants, and 4.56% of them were diagnosed with CP. The incidence was higher among males with birth weight ≤1000g. There was an incidence of 5.21% of visual disability, with 0.5% of children being blind in one or both eyes. Cerebral palsy was associated with retinopathy of prematurity, severe intraventricular haemorrhage, and periventricular leukomalacia, in particular cystic periventricular leukomalacia. | {
"pile_set_name": "PubMed Abstracts"
} |
The clinical significance of coagulation and the inflammatory response in autoimmunity.
Maintenance of normal blood flow requires equilibrium between procoagulant and anticoagulant factors; occasionally, procoagulant activity predominates, leading to clot formation; frequently, tissue damage is the triggering factor. Hereditary factors, primary or acquired, play a role in the development of thrombosis. Primary thrombophilia is associated with hereditary factors, which promote hypercoagulability because natural anticoagulants are not exerting their activity. On the other hand, acquired thrombophilia may occur associated to autoimmune diseases, cancer, surgical procedures, pregnancy, postpartum period, and obesity. Activation of the coagulation system is characterized by the co-participation of inflammatory response components, factors related to the subjacent disease, and other procoagulant factors. The study of patients with thrombosis should include both inflammatory and autoimmune response markers. | {
"pile_set_name": "PubMed Abstracts"
} |
Anticonvulsant activity of pyrrolo[1',2':1,2]imidazo[4,5-b]pyridines, pyrrolo[2',1':2,3]imidazo[4,5-c] pyridines and pyrrolo[2,1-f]purines in DBA/2 mice.
1. The behavioural and anticonvulsant effects of eight pyrroloimidazopyridines (PI1a-d and PI2a-d) and four pyrrolopurines (PP) were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated in DBA/2 mice on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. 3. Hypothermic activity was observed after the highest doses of the pyrroloderivatives studied. 4. Our study demonstrated that the anticonvulsant effect of pyrroloimidazopyridines (PI1-7,8,8a,9-tetrahydro-6H-pyrrolo-[1',2':1,2]imidazo[4,5-b]pyrid in-6- ones) and pyrrolopurines (PP) was generally better than corresponding pyrrolobenzimidazoles (PB) and pyrroloimidazopyridines (PI2-5,5a,6,7-tetrahydro-8H-pyrrolo[2',1':2,3]imidazo[4,5-c]pyridin-8- ones) and, in some cases, comparable to that of phenytoin and desmethylclobazam. 5. The anticonvulsant potency of the derivatives studied cannot be directly related to their lipophilicity. | {
"pile_set_name": "PubMed Abstracts"
} |
Emergency surgery for native mitral valve endocarditis: the impact of septic and cardiogenic shock.
Limited information exists about the real impact of the etiology of shock on early and late outcome after emergency surgery in acute native mitral valve endocarditis (ANMVE). This multicenter study analyzed the impact of the etiology of shock on early and late outcome in patients with ANMVE. Data were collected in eight institutions. Three hundred-seventy-nine ANMVE patients undergoing surgery on an emergency basis between May 1991 and December 2009 were eligible for the study. According to current criteria used for the differential diagnosis of shock, patients were retrospectively assigned to one of three groups: group 1, no shock (n=154), group 2, cardiogenic shock (CS [n=118]), and group 3, septic shock (SS [n=107]). Median follow-up was 69.8 months. Early mortality was significantly higher in patients with SS (p<0.001). At multivariable logistic regression analysis, compared with patients with CS, patients with SS had more than 3.8 times higher risk of death. That rose to more than 4 times versus patients without shock. In addition, patients with SS had 4.2 times and 4.3 times higher risk of complications compared with patients with CS and without shock, respectively. Sepsis was also an independent predictor of prolonged artificial ventilation (p=0.04) and stroke (p=0.003) whereas CS was associated with a higher postoperative occurrence of low output syndrome and myocardial infarction (p<0.001). No difference was detected between groups in 18-year survival, freedom from endocarditis, and freedom from reoperation. Our study suggests that emergency surgery for ANMVE in patients with CS achieved satisfactory early and late results. In contrast, the presence of SS was linked to dismal early prognosis. Our findings need to be confirmed by further larger studies. | {
"pile_set_name": "PubMed Abstracts"
} |
Messenger RNA for the coat protein of tobacco mosaic virus.
TMV RNA is not an efficient template for translation of the viral coat protein, in spite of containing nucleotide sequences coding for the protein. Efficient translation requires the prior synthesis within infected cells of a smaller RNA carrying only a portion of the information encoded in the whole genome. | {
"pile_set_name": "PubMed Abstracts"
} |
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