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Design, synthesis and biological evaluation of quinoline derivatives as HDAC class I inhibitors.
Inhibition of histone deacetylase (HDAC) has been regarded as a potential therapeutic approach for treatment of multiple diseases including cancer. Based on pharmacophore model of HDAC inhibitors, a series of quinoline-based N-hydroxycinnamamides and N-hydroxybenzamides were designed and synthesized as potent HDAC inhibitors. All target compounds were evaluated for their in vitro HDAC inhibitory activities and anti-proliferative activities and the best compound 4a surpass Vorinostat in both enzymatic inhibitory activity and cellular anti-proliferative activity. In terms of HDAC isoforms selectivity, compounds 4a exhibited preferable inhibition for class I HDACs, especially for HDAC8, the IC50 value (442 nM) was much lower than that of Vorinostat (7468 nM). Subsequently, we performed class I & IIa HDACs whole cell enzyme assay to evaluate inhibitory activity in whole cell context. Compounds 4a and 4e displayed much better cellular activity for class I HDACs than that for class IIa HDACs, which indicated that 4a and 4e might be potent class I HDAC inhibitors. Meanwhile, flow cytometry analysis showed that compound 4a and 4e can promote cell apoptosis in vitro. | {
"pile_set_name": "PubMed Abstracts"
} |
Endoscopic robot-assisted extended thymectomy by subxiphoid approach with sternal lifting: feasibility in the pig.
In the search for novel approaches to thoracoscopic thymectomy we assessed the feasibility of a subxiphoid approach using computer-enhanced instruments and sternal lifting. In 12 pigs, after lifting of the sternum, ports were placed subxiphoid (stereoscope) and in the left and right fourth intercostal space (instruments). Using computer-enhanced instruments, dissection of the thymus and anterior mediastinal fat pads was started at the diaphragm and continued cephalad. After setup of the robot system (23 +/- 6 min, mean +/- SD), the thymus, including both superior horns, and fat pads in the anterior mediastinum and cardiophrenic angles were dissected (109 +/- 23 min), with excellent view of the phrenic nerves. Visual inspection after sternotomy after the procedure showed all thymic and fatty tissue was removed. In the pig, endoscopic extended thymectomy can be safely performed by subxiphoid access using computer-enhanced instruments, sternal lifting, and three ports total. | {
"pile_set_name": "PubMed Abstracts"
} |
Autosomal dominant brachydactyly, coloboma and anterior segment dysgenesis.
A three-generation family presenting with ocular developmental abnormalities, including anterior segment dysgenesis and coloboma, associated with brachydactyly and clinodactyly is presented. Several conditions incorporating ocular and bony limb abnormalities have been described. However, we believe that this family manifests a previously undescribed syndrome due to autosomal dominant or possibly x-linked inheritance with variable expression. | {
"pile_set_name": "PubMed Abstracts"
} |
N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats.
Estrogen interacts with N-methyl-d-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In the hippocampus, estrogens increase both dendritic spine density and synapse number, and NMDA antagonists block these effects. This plasticity in the hippocampus mediated by estrogen may be of particular importance in the context of aging when estrogen levels change and cognitive function is often impaired. Therefore, the present study was designed to investigate effects of aging and reproductive status on NMDA receptor (NR) subunit mRNA levels in the hippocampus. NR1, NR2A, and NR2B mRNA levels were measured by RNase protection assay in young (3-4 month), middle-aged (12-13 month), and aged (24-25 month) Sprague-Dawley rats in different phases of the estrous cycle in cycling animals and in acyclic subjects. Our results demonstrated that NMDA receptor subunit mRNA levels were much more prominently affected by the chronological age than by the reproductive status of the animals. Age-related changes were observed in NR1, NR2A, and NR2B in the ventral hippocampus and in NR1 and NR2B in the dorsal hippocampus. However, the only relationship with reproductive status was seen for NR1 mRNA, and this was restricted to the ventral hippocampus. An interaction between chronological age and reproductive status was found, with higher levels of NR1 mRNA seen in young animals in proestrus than in those in diestrus I (high and low estrogen levels, respectively). However, this relationship was not seen in the aged subjects. These results demonstrate that the hippocampus is subjected to age-related alterations in NMDA receptor subunit mRNA levels and that animals of different ages are influenced differently by reproductive status. This shift in the NMDA receptor mRNA levels may be a possible molecular mechanism contributing to alterations in cognitive behavior during normal aging. | {
"pile_set_name": "PubMed Abstracts"
} |
Marked resorption of the thumb proximal phalanx following open reduction and K-wire fixation of a phalangeal neck fracture in a child: case report.
We report on a child with nonunion of a phalangeal neck fracture of the thumb following open reduction and K-wire fixation. There was progressive resorption of the proximal but not the distal fracture fragment. Successful reconstruction was obtained using a non-vascularized iliac crest bone graft. | {
"pile_set_name": "PubMed Abstracts"
} |
Allotype analysis to distinguish the origin of varicella-zoster virus immunoglobulin G after allogeneic stem cell transplantation.
Varicella-zoster virus (VZV) reactivation is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although previous studies have revealed that cellular immunity is important for suppressing reactivation, the role of humoral immunity against VZV has been poorly evaluated. We analyzed inherited polymorphisms in the immunoglobulin G (IgG) heavy chain constant regions of 50 HSCT recipient-donor pairs to distinguish donor-derived and recipient-derived antibodies. Twelve pairs were informative regarding the origin of IgG, since either the donors (n = 3) or recipients (n = 9) were homozygous null for the IgG1m(f) allotype. In these 9 homozygous-null recipients, allotype-specific IgG against VZV were measured by enzyme-linked immunosorbent assay and compared with measles-IgG. All 9 homozygous-null recipients were monitored for more than 1 year after HSCT, with (n = 4, localized zoster) or without (n = 5) clinical VZV disease. In 3 patients with VZV disease, donor-derived IgG against VZV was elevated between 500 to 700 days after HSCT after the episode of VZV disease. In 1 patient who suffered from VZV disease just before HSCT, donor-derived VZV IgG was elevated within 3 months after HSCT. On the other hand, 2 patients who received reduced-intensity conditioning (RIC) transplantation from an IgG1m(f) null donor maintained recipient-derived IgG against VZV for more than 1 year, whereas it was decreased within 3 months in 1 recipient who received conventional conditioning. In conclusion, the production of anti-VZV IgG by recipient plasma cells persists long after RIC. In patients without symptomatic VZV reactivation, donor-derived anti-VZV IgG did not reach titers comparable to those measured in healthy virus carriers. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of GAC layer on the performance of gravity-driven membrane filtration (GDM) system for rainwater recycling.
Gravity-driven membrane filtration (GDM) is promising for decentralized rainwater recycling, owing to low maintenance and energy consumption. However, the organic removal by GDM process is sometimes undesirable and the quality of the permeate cannot meet the standard of water reuse. To improve this, granular activate carbon (GAC) was added as a particle layer on the membrane surface of GDM system. Additionally, a system with sand addition and a system with no particle addition were trialed as comparisons, to study the combined effects of particle hindering and adsorption on the removal efficacy of organics and the development of permeate flux. Results showed that GDM with a GAC layer improved removal efficiency of organics by 25%, and that GAC enhanced removal of florescent compounds (e.g., aromatic proteins, tryptophan proteins and humics), compared with the other two systems. Additionally, the permeate flux in three systems stabilized after Day 25, and kept stable until the end of the operation. However, the presence of GAC layer decreased the level of stable flux (3.2 L/m2h) compared with the control system (4.5 L/m2h). The factors responsible for the lower flux and severe membrane fouling in GAC layer assisted system were the combined effects of particle and adsorption which led to a denser bio-fouling layer with higher amount of biomass and extracellular polymeric substances contents (proteins and polysaccharides). Resistance distribution analyses revealed that GAC layer mainly increased hydraulically reversible resistance (occupied 93%) of the total resistance, indicating that the flux could be recovered easily by simple physical cleaning. | {
"pile_set_name": "PubMed Abstracts"
} |
Solar photothermochemical reaction and supercritical CO2 work up for a fully green process of preparation of pure p-nitrobenzyl bromide.
It has been reported by us recently that p-nitrobenzyl bromide (PNBBr) can be synthesized from p-nitrotoluene (PNT) in high isolated yield with respect to available bromine in 2:1 Br(-)-BrO3(-) employed as brominating reagent. The reaction was conducted in ethylene dichloride (EDC) and the substrate was taken in excess to suppress dibromo impurity formation. The product was "cold crystallized" from the reaction mass and the mother liquor was recycled in the subsequent batch thereby eliminating organic discharge. The present work attempts to further advance the synthesis of this commercially important molecule employed in protection-deprotection strategies. Herein its successful synthesis employing neat substrate and solar radiation as the sole energy source to drive this photothermochemical reaction is reported. Further, 100% pure PNBBr could be isolated from the solid reaction mass in 87% yield by leaching out the excess substrate through supercritical CO2 (Sc-CO2) extraction. The reaction was therefore accomplished cleanly in all respects and with low carbon footprint. | {
"pile_set_name": "PubMed Abstracts"
} |
Brief report: candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity.
Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) share some pathophysiologic bases as evidenced by individual and familial polyautoimmunity and common susceptibility genetic factors. With regard to the latter, there has been a recent shift from the "common variant" to the "rare variant" paradigm, since rare variants of TNFAIP3 and TREX1 with large effect sizes have recently been discovered in SLE. The present study was undertaken to investigate whether rare variants of TNFAIP3 and TREX1 are also associated with SSc. TREX1 single-nucleotide polymorphisms (SNPs) rs3135946, rs7626978, rs3135943, and rs11797 and TNFAIP3 SNPs rs9494883, rs72063345, rs5029939, rs2230926, rs117480515, and rs7749323 were genotyped in a discovery set (985 SSc patients and 1,011 controls), and replication analysis of the most relevant results was performed in a second set (622 SSc patients and 493 controls). No association between TREX1 variants and SSc was observed. For TNFAIP3, we first demonstrated that a low-frequency variant, rs117480515, tagged the recently identified TT>A SLE dinucleotide. In the discovery sample, we observed that all tested TNFAIP3 variants were in linkage disequilibrium and were associated with SSc and various SSc subsets, including the polyautoimmune phenotype. We subsequently genotyped rs117480515 in the replication sample and found it to be associated solely with the SSc polyautoimmune subset (odds ratio 3.51 [95% confidence interval 2.28-5.41], P = 8.58 × 10(-9) ) in the combined populations. Genotype-messenger RNA (mRNA) expression correlation analysis revealed that the TNFAIP3 rs117480515 risk allele was associated with decreased mRNA expression. The present findings establish the TNFAIP3 locus as a susceptibility factor for the subset of SSc with a polyautoimmune phenotype. Our results support the implication of rare/low-frequency functional variants and the critical role of A20 in autoimmunity. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of treatment with dexamethasone on protein intake in adult and old Lou/c/jall rats.
A deleterious decrease of protein intake had been evidenced in Lou/c/jall rats during ageing. This result could be induced by an impaired regulation of feeding behaviour. Glucocorticoids inducing specific amino-acid needs for gluconeogenesis and for the synthesis of inflammatory proteins by the liver, we investigated the age-related effect of a 4-days treatment with dexamethasone (DEX) on caloric and protein intake. Males and females aged 7, 19, 25 and 31 months received 573.6 +/- 65.6 microg/(kg day) of dexamethasone via the drinking water. Body weight (BW), caloric and macronutrients intakes were monitored during treatment and during 10 days after the treatment. A strong hypophagia was seen during treatment in all groups, which was mainly due to a decrease in fat intake. In the same time, rats maintained their protein intake so that protein became the main macronutrient of the diet in most of the groups. However, older males showed a lesser efficiency in adjusting their diet. These results are in agreement with previous data obtained in a protein deprivation study. They lead to the conclusion that the loss of appetite for protein in old age probably does not reflect a loss of ability to choose the needed amount of protein. We can hypothesise that the decrease of protein intake in old rats could be due to some inadequacy of casein to the metabolic requirement of aged animals. | {
"pile_set_name": "PubMed Abstracts"
} |
Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy.
Our study investigated the usefulness of contrast-enhanced MR imaging for accurately measuring the size of residual tumor after patients have undergone neoadjuvant (pre-operative) chemotherapy. The imaging analysis method was optimized for identifying residual disease in the treated breast. Tumor sizes measured on the MR images and at the clinical examination were compared with the size of residual disease measured at pathology after surgery. Before undergoing surgery, 52 patients were imaged before and after receiving neoadjuvant chemotherapy. For each patient, specific malignancy criteria were applied to MR images before chemotherapy to identify the location of tumor, and residual disease was then identified as any remaining enhancement in the same area on the MR images after chemotherapy. Residual tumor size was measured using both the MR technique and the clinical examination findings, and the degree of measurement error for each method was assessed in comparison with the pathologic findings. The correlation with pathology was an r value of 0.89 for MR measurements compared with an r value of 0.60 for clinical measurements. In addition, MR imaging revealed all cases of residual disease, whereas clinical assessment resulted in five false-negative interpretations in the 52 treated lesions. The high correlation between measurements of residual disease obtained on MR images and those obtained at pathology validates the sensitivity of MR imaging of the breast after chemotherapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Proteasome degradation of GRK2 during ischemia and ventricular tachyarrhythmias in a canine model of myocardial infarction.
Arrhythmia-prone subepicardial border zone (EBZ) tissue demonstrates decreased G protein receptor kinase 2 (GRK2) activity and increased sensitivity to isoproterenol 6-24 h after coronary artery ligation (CAL) in the dog. With the use of a semiquantitative immunofluorescence technique, the relative fluorescence intensity (RF) of GRK2 in EBZ decreased to 24% of that in a remote site (RS) (P < 0.01, n = 30 cells from 3 dogs), whereas GRK5 RF did not change. Confocal studies of cardiac tissue from transgenic mice overexpressing GRK2 validated the use of a semilogarithmic relationship between RF and GRK2 activity. As shown with the use of quantitative real-time RT-PCR, both GRK2 and GRK5 mRNA were not decreased at 24 h in EBZ (n = 6 dogs) relative to RS control, indicating that the decrease of GRK2 in the EBZ is likely due to posttranscriptional degradation following CAL. Pretreatment of six dogs with the selective proteasome inhibitor bortezomib provided 100% (EBZ) and 50% (infarct) protection against loss of GRK2 at 24 h. There was an absence of rapid (>300 beats/min) and very rapid (>360 beats/min) ventricular triplets that are highly predictive of sudden cardiac death during ECG monitoring in the bortezomib-pretreated animals in contrast to nonpretreated infarcted animals. We have demonstrated that the dramatic decrease in GRK2 in cardiac ischemic tissue can be largely blocked by prior proteasome blockade and that this is associated with significant cardioprotection against malignant ventricular tachyarrhythmias. | {
"pile_set_name": "PubMed Abstracts"
} |
Inhibitory effect of rat amylin on the insulin responses to glucose and arginine in the perfused rat pancreas.
Amylin, a 37-amino acid polypeptide, is the main component of amyloid deposits in the islets of Langerhans, and has been identified in the B-cell secretory granules. We have investigated the effect of rat amylin on the insulin and glucagon release by the isolated, perfused rat pancreas. Amylin infusion at 750 nM, markedly reduced unstimulated insulin release (ca. 50%, P less than 0.025), whereas it did not modify glucagon output. At the same concentration, amylin also blocked the insulin response to 9 mM glucose (ca. 80%, P less than 0.025) without affecting the suppressor effect of glucose on glucagon release. The inhibitory effect of amylin on glucose-induced insulin secretion was confirmed by lowering the amylin concentration (500 nM) and increasing the glucose stimulus (11 mM); again, no effect of amylin on glucagon release was observed. Finally, amylin, at 500 nM, reduced the insulin response to 3.5 mM arginine (ca. 40%, P less than 0.025) without modifying the secretion of glucagon elicited by this amino acid. It can be concluded that, in the rat pancreas, the inhibitory effect of homologous amylin on unstimulated insulin secretion, as well as on the insulin responses to metabolic substrates (glucose and arginine), favours the concept of this novel peptide as a potential diabetogenic agent. | {
"pile_set_name": "PubMed Abstracts"
} |
Mechanical modeling of biological cells in microinjection.
Microinjection is an effective technique to introduce foreign materials into a biological cell. Although some semi-automatic and fully-automatic microinjection systems have been developed, a full understanding of the mechanical response of biological cells to injection operation remains deficient. In this paper, a new mechanical model based on membrane theory is proposed. This model establishes a relationship between the injection force and the deformation of biological cells with the quasi-static equilibrium equations, which are solved by the Runge-Kutta numerical method. Based on this model, other mechanical responses can also be inferred, such as the effect of the injector radius, the membrane stress and tension distribution, internal cell pressure, and the deformed cell shape. To verify the proposed model, experiments are performed on microinjection of zebrafish embryos at different developmental stages and medaka embryos at the blastula stage. It is demonstrated that the modeling results agree well with the experimental data, which shows that the proposed model can be used to estimate the mechanical properties of cell biomembranes. (In this paper, biomembrane refers to the membrane-like structures enveloping cells.) | {
"pile_set_name": "PubMed Abstracts"
} |
Reduced beta 2-adrenoceptor responsiveness in exercise-induced asthma.
Beta-adrenoceptor responsiveness was studied both in vivo and in vitro in patients with exercise-induced asthma (EIA), asthmatic patients without EIA (NEIA), and control subjects. All subjects were age- and sex-matched and without medication at least one week prior to the tests. In vivo, beta-adrenoceptor responsiveness was evaluated by plasma concentration-effect studies for intravenously infused isoprenaline (0.02-0.1 micrograms X kg-1 X min-1). Mainly beta 2-adrenoceptor mediated responses to isoprenaline, ie, decreases in diastolic blood pressure and increases in plasma cyclic AMP, were reduced in EIA patients but not in NEIA patients. Heart rate and plasma glycerol responses to isoprenaline did not differ between the groups. In vitro, the beta 2-adrenoceptor mediated accumulation of cyclic AMP in lymphocytes stimulated by isoprenaline was attenuated (p less than 0.05) in EIA patients, whereas the beta 2-adrenoceptor responsiveness of lymphocytes from NEIA patients was normal. Thus, beta 2-adrenoceptor mediated responses were reduced both in vivo and in vitro in EIA patients, but not in NEIA patients. This finding that beta 2-adrenoceptor responsiveness was reduced only in a subgroup of asthmatic patients could explain some of the controversies in the literature concerning beta-adrenoceptor function in asthma. | {
"pile_set_name": "PubMed Abstracts"
} |
Degenerate binding of immunogenic peptides to HLA-DR proteins on B cell surfaces.
Binding of linear fragments of protein antigens to class I or class II molecules of the MHC is necessary for the stimulation of a cellular immune response. This report describes the binding of a biotinylated T cell determinant from influenza hemagglutinin to class II proteins on the surface of Epstein-Barr virus-transformed B lymphocytes. The rapid, simple, and quantitative binding assay involves flow cytometric analysis of transformed B cells stained with fluoresceinated streptavidin following incubation with the biotinylated peptide. Binding of the biotinylated peptide required cell surface expression of human class II molecules, and was inhibited by an anti-HLA-DR monoclonal antibody as well as the unbiotinylated natural determinant. Rates of association and dissociation of the peptide were similar to those reported for purified MHC class II proteins, and the peptide bound only approximately 1% of the DR molecules expressed on the cell surface. When assayed on many different DR-homozygous B cell lines, the biotinylated hemagglutinin T cell determinant bound to HLA-DR on each cell line. The degeneracy of peptide binding to B cell lines was not unique to the hemagglutinin peptide because three other biotinylated T cell determinants failed to bind to class II deficient B-lymphoblastoid cells but bound to varying degrees to multiple DR-homozygous lines. | {
"pile_set_name": "PubMed Abstracts"
} |
[Update on diagnosis and treatment of normotensive hydrocephalus (chronic hydrocephalus of the adult)].
Normal pressure hydrocephalus, or adult chronic hydrocephalus, is a relatively unknown entity. Classically, this disease is characterized by progressive dementia, gait disturbance, and urinary incontinence. Despite an increase in the prevalence of this type of dementia due to longer life expectancy, its diagnosis and treatment remain controversial. Recent studies have reported that the percentage of patients who show clinical improvement after shunting is still low and that the complication rate is excessively high. However, our experience and that of other authors indicates that the percentage of improvement after shunting can be greater than 80% and the complication rate can be low if a strict diagnostic protocol is applied and if the most appropriate valve is selected, based on the hydrodynamic characteristics of the shunt. The aim of this review is to provide an update of the clinical features, diagnosis and treatment of adult chronic hydrocephalus. We also discuss the diagnostic and treatment protocols applied in our centre in patients with suspected adult chronic hydrocephalus. | {
"pile_set_name": "PubMed Abstracts"
} |
Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model.
For glioma, temozolomide (TMZ) is a commonly used chemotherapy drug and photodynamic therapy (PDT) is an important adjuvant therapy. The aim of this study was to evaluate the effect of their combination for the treatment of glioma. A rat C6 glioma model using male Wistar rats (n=180) weighing 280-300 g was established. Glioma-bearing rats (n=100) were treated with mock, hematoporphyrin monomethyl ether (HMME), laser or PDT. The expression of P-glycoprotein (P-gp) in endothelial cells of the blood-tumor-barrier and in glioma tissues was detected using immunohistochemistry and western blot, respectively. Glioma-bearing rats (n=40) were treated with normal saline, TMZ (60 mg/m(2) for five consecutive days), PDT (630 nm for 10 min) or a combination of TMZ and PDT. TMZ concentration in glioma tissues was detected using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and cell death was observed using transmission microscopy. Concurrently, another batch of 40 glioma-bearing rats was subjected to the same treatment, and the survival of these rats was estimated using Kaplan-Meier analysis. PDT significantly decreased the expression of P-gp in endothelial cells comprising the blood-tumor-barrier and in glioma tissues. The combination of TMZ with PDT significantly increased TMZ concentration in glioma tissues, enhanced glioma cell apoptosis and prolonged the median survival of glioma-bearing rats. The combination of PDT with TMZ shows synergistic effect in rat C6 glioma model, indicating its potential clinical use in glioma treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Two effects of context on the presence/absence of connecting segments.
Stimulus A consisted of two proximal brackets with colinear lines separated by small gaps. Stimulus B was a square-like rectangle produced by inserting connecting segments into the gaps. Stimulus A was frequently represented as B (i.e., as closed). Following Pomerantz and Pristach (1989) and Treisman and Paterson (1984), perhaps A produced a closure emergent feature that was salient but otherwise independent of other features. However, adding the same two vertical lines (context) to both A and B produced a contrasting division outcome, even though the putative closure emergent feature was an element of the A+context stimulus, and even though it matched a physical feature of the B+context stimulus. Therefore, this emergent feature did not produce the closure. Two additional experiments indicated that the two context lines made the two connecting segments more visible--a context-produced increase in visibility occurred that is not comparable to other known evidence of perceptual improvement. This greater visibility also indicates that the division was not due to the two context lines inhibiting the perception of the two connecting segments, and the closure was not due to good continuation. | {
"pile_set_name": "PubMed Abstracts"
} |
Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low kidney uptake.
We have recently shown that accumulation in mouse kidneys of technetium-99m labeled phosphorodiamidate morpholinos (MORFs) increases with the number of cytosines in the base sequence. To improve tumor/kidney ratios in tumored mice, pretargeting studies were performed with a cytosine-free MORF. An 18-mer MORF (5'-TCTTCTACTTCACAACTA) was conjugated to the anti-CEA antibody MN14 (Immunomedics) and administered to nude mice bearing LS174T tumors. Thereafter, the (99m)Tc-labeled cytosine-free cMORF (5'-TAGTTGTGAAGTAGAAGA-amide-MAG(3)) was administered. For comparison, the identical study was repeated but with our original pair of 18-mer MORFs (5'-GGGTGTACGTCACAACTA-conjugated MN14 and (99m)Tc-labeled 5'-TAGTTGTGACGTACACCC-amide-MAG(3)). Surface plasmon resonance was used to show that the hybridization affinities of the original and the modified pair of MORFs were essentially equal. Hybridization of the cytosine-free cMORF-(99m)Tc to MN14-MORF was demonstrated in vitro by size-exclusion high-performance liquid chromatography. At 3 h, kidney levels in normal mice were 2.0%ID/organ for the modified cMORF vs. 4.1%ID/organ for the original cMORF sequence, while at 24 h, these values were 0.9% vs 1.8%ID/organ. Pretargeting studies in tumored mice receiving 25 microg of conjugated antibody, 0.5 microg of labeled cMORF 48 h later, followed by imaging and sacrifice at 3 h showed that kidney levels were reduced using the cytosine-free cMORF. Moreover, tumor accumulation was about 3.6%ID/g and was independent of sequence. The whole-body images clearly reflected the improved tumor to kidney ratios. By choosing a cytosine-free base sequence for pretargeting studies, kidney accumulation of cMORF-(99m)Tc was reduced without adversely influencing tumor accumulation. The lowering of kidney radioactivity levels in this way may be important to reduce toxicity to this organ in connection with pretargeting radiotherapy studies. | {
"pile_set_name": "PubMed Abstracts"
} |
Pharmacodynamic-mediated effects of the angiogenesis inhibitor SU5416 on the tumor disposition of temozolomide in subcutaneous and intracerebral glioma xenograft models.
The objective of this study was to determine the tumor distribution of temozolomide, an alkylating agent, in the absence and presence of the angiogenesis inhibitor 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]indolin-2-one (SU5416), a specific vascular endothelial cell growth factor receptor 2 inhibitor. The study was conducted in nude rats bearing either subcutaneous or intracerebral tumors that overexpressed vascular endothelial cell growth factor. For both tumor locations, animals were assigned to either of two treatment groups, SU5416 (25 mg/kg, dissolved in dimethyl sulfoxide) or vehicle control, dimethyl sulfoxide (710 microl/kg) administered i.p. every day for a total of nine doses. Twenty-four hours after the last dose of SU5416 or dimethyl sulfoxide, temozolomide was administrated as a steady-state infusion regimen designed to achieve target plasma concentrations (Cp) of 20 microg/ml. In addition to the measurement of temozolomide Cp, tumor interstitial fluid unbound concentrations of temozolomide were evaluated by microdialysis. In subcutaneous tumors, SU5416 treatment produced a 24% reduction in steady-state temozolomide Ct values (p < 0.05) as well as 21% reductions in tumor/plasma concentration ratios (Ct/Cp; p = 0.11) compared with controls. In intracerebral tumors, steady-state temozolomide Ct and Ct/Cp ratios were significantly increased by 2-fold in the SU5416 treatment group compared with control. The apparent paradoxical effect of SU5416 on the tumor disposition of temozolomide in subcutaneous and intracerebral tumors is discussed in the context of physiological changes (for example, interstitial fluid pressure and microvessel density) and the sampling region in the tumor. It is proposed that the net balance of antiangiogenic drug-mediated pharmacodynamic actions will determine how drug disposition in tumors may be affected. | {
"pile_set_name": "PubMed Abstracts"
} |
Orientational distributions and nematic order of rodlike magnetic nanoparticles in dispersions.
Using small-angle neutron scattering (SANS), we have investigated the orientational order of iron nanoparticles dispersed in cyclohexanone. The particles have rodlike shape and size distributions with an average length of 200 nm and an average diameter of 25 nm. SANS shows an anisotropy, which is a measure of orientational order, in magnetic dispersions with a volume fraction of 3.2% and 3.9% iron particles in shear flow and/or magnetic field. The scattering anisotropy can be fitted by a model assuming an Onsager distribution of the orientation of the particles in shear flow. The orientational distribution of particles oriented by a magnetic field can be described by a different model assuming the Maier-Saupe orientational distribution for uniaxial ferromagnetic particles. The orientational distribution parameter m for the Maier-Saupe distribution or alpha for the Onsager distribution and the orientational order parameter S have been determined at shear rates gamma[over ] of to 0-4000 s(-1) and in magnetic fields of 0-18 mT. The S values indicate that the particles start to orient either in a shear flow of 100 s(-1) or in a magnetic field of 6 mT. Applying only shear results in an orientational order, with the dispersion returning to the disordered state when the shear rate is decreased to zero. In sharp contrast, application of magnetic fields greater than 6 mT results in orientational order in the field-increasing cycle, and two-thirds of the orientational order remains when the field is decreased to zero. This shows that the order in a magnetic field is different from the order in a shear flow, the action of magnetizing the particles along a certain direction is irreversible, and the orientational order parameter exhibits hysteresis. | {
"pile_set_name": "PubMed Abstracts"
} |
A score test for testing a zero-inflated Poisson regression model against zero-inflated negative binomial alternatives.
Count data often show a higher incidence of zero counts than would be expected if the data were Poisson distributed. Zero-inflated Poisson regression models are a useful class of models for such data, but parameter estimates may be seriously biased if the nonzero counts are overdispersed in relation to the Poisson distribution. We therefore provide a score test for testing zero-inflated Poisson regression models against zero-inflated negative binomial alternatives. | {
"pile_set_name": "PubMed Abstracts"
} |
Patient and parental scar assessment after single incision versus standard 3-port laparoscopic appendectomy: long-term follow-up from a prospective randomized trial.
Single site laparoscopy for appendectomy is a technique with several case series suggesting a cosmetic advantage, but without prospective comparative data. We conducted a prospective, randomized trial comparing single site laparoscopic appendectomy to the standard 3-port approach, including scar assessment at early and long-term follow-up. Enrolled patients over 12years old and parents of patients less than 12years old were asked to complete the validated Patient Scar Assessment Questionnaire (PSAQ) at early follow-up around 6weeks and by phone after 18months. The PSAQ consists of 4 scored subscales: Appearance, Consciousness, Appearance Satisfaction, and Symptom Satisfaction. Each subscale has a set of questions with a 4-point categorical response (1=most favorable, 4=least favorable). The sum of the scores quantifies each subscale. Early questionnaires were obtained from 98 3-port and 100 single-site patients with the single-site approach producing superior overall scar assessment (P=0.003). By telephone follow-up, questionnaires were completed by 49 3-port and 56 single-site patients at a median of 25 (18-32) months. In this longer-term follow-up, overall scar assessment was not significantly different between groups (P=0.06). Patients or parents express superior scar assessment with the single site approach at early follow-up, but this difference disappears in the long-term. | {
"pile_set_name": "PubMed Abstracts"
} |
Acute relief of epigastric pain by antacid in duodenal ulcer patients.
Thirty-six duodenal ulcer patients participated in a randomized controlled trial of the immediate effect of a liquid antacid preparation (Link) and placebo on epigastric pain. The patients recorded the effect of a total of 143 doses of antacid and 148 doses of placebo. Marked or complete relief of pain 30 min after ingestion was found after 62% of the antacid doses and after 52% of the placebo doses. The average effect of antacid was better than the effect of placebo in 21 patients, worse in 8 and equal in 7 patients. This difference in favour of antacid is statistical significant (p less than 0.05) and therefore it is concluded that antacid is more effective than placebo in relieving epigastric pain in duodenal ulcer patients, although the therapeutic gain is small. | {
"pile_set_name": "PubMed Abstracts"
} |
Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid disease.
Fetuses from mothers with autoimmune thyroid disease (AITD) may be affected by antithyroid antibodies, antithyroid drugs, and iodine. The study correlated fetal free T(4) (fT4) with fetal ultrasound parameters and maternal thyroid function, thyroid antibodies, and medication dose from mothers with AITD. The study was designed as a prospective cohort study and conducted in an academic referral center. Eighty-three of 85 women with AITD completed the study; 38 were treated for hyperthyroidism and 25 for hypothyroidism, and 20 were euthyroid. Outcomes were as follows: 1) fetal-fT4, TSH, ultrasound parameters (morphology, biometrics, heart rate); and 2) maternal-fT4, TSH, antithyroid drug dose, and antithyroid antibodies, thyroid peroxidase and TSH receptor (TRAK). Parameters were determined at the same time, between the 22nd and 33rd wk gestation. A total of 48.3% of fetuses from hyperthyroid mothers, 60% of fetuses from hypothyroid mothers, and 10% of fetuses from euthyroid mothers had elevated fT4 levels (P = 0.006). In hypothyroid mothers, the presence of both thyroid antibodies was related to fetal hyperthyroidism, whereas absence was related to fetal euthyroidism (P = 0.019). Hyperthyroid mothers (TRAK-positive, thyroid peroxidase-negative) with hyperthyroid fetuses had significantly higher mean TRAK than hyperthyroid mothers with euthyroid fetuses (13.7 vs. 3.7 IU/liter; P = 0.02). Fetal fT4 correlated weakly negatively with maternal TSH within the normal range, but not with ultrasound parameters or with antithyroid drug dose. High fetal fT4 levels were unexpectedly frequent in women with AITD, including maternal autoimmune hypo- and hyperthyroidism. Further studies are needed, as well as noninvasive methods to assess fetal thyroid function. | {
"pile_set_name": "PubMed Abstracts"
} |
Midwifery and society in restoration York.
This article is a micro-historical study of the social networks of an elite mid-wife in seventeenth-century England, and discusses the implications of these networks for our understanding of early modem midwifery. Bridget Hodgson was the daughter-in-law to the former Lord Mayor of York, and closely connected to some of the city's most influential families. Analysis of the connections found in her will and the depositions from a defamation trial in which she was involved illustrates Hodgson's place among York's elite, but also indicates that her work as a midwife took her outside of these circles. This article also compares Hodgson's experience with that of her maidservant and deputy, discussing the different meanings that midwifery could have for its practitioners, depending on their social background. Testimony from the defamation case indicates the ways in which her work as a midwife shaped her relationship to parish authorities and to the female community. Midwives were expected to report illegitimate births to parish officials, an obligation which overlapped with female efforts to control the sexuality of neighbourhood women through gossip. This article highlights the complexity of the midwife's place in early modern society, and contributes to our understanding of this important class of women. | {
"pile_set_name": "PubMed Abstracts"
} |
Nosocomial bacterial and fungal meningitis in children; an eight year national survey reporting 101 cases. Pediatric Nosocomial Meningitis Study Group.
One hundred and one cases of nosocomial meningitis in children from a national survey over 8 years have been analyzed for risk factors and outcome. From 101 cases, 115 organisms were isolated. Seventy six were Gram-positive bacteria, 29 were Gram-negative and there were ten fungal isolates. Major risk factors for acquisition of nosocomial meningitis were neurosurgery (70.2%), ventriculoperitoneal shunt (42.9%), prior therapy with broad spectrum antibiotics (64.1%), central venous catheter (94.5%), premature neonates with very low birth weight (32.8%) and total parenteral nutrition (68.8%). Overall attributable mortality was 14. 9%; in bacterial infection it was 13.2% and in fungal nosocomial meningitis, 30.0%. Higher mortality was significantly related to perinatal pathology with CNS abnormality, prematurity polymicrobial infection with Enterobacteriaceae and concomitant bacteraemia. Prematurity in neonates, very low birth weight and infection with Enterobacteriaceae were significantly associated with a worse outcome. | {
"pile_set_name": "PubMed Abstracts"
} |
Thyroid gland ectopias.
Failures of descent of the medial anlage of the thyroid and incomplete obliteration of its vertical tract lead to midline or near-midline ectopias such as lingual thyroid and thyroglossal cysts. Each poses special diagnostic and therapeutic considerations. "Ectopias" of the thyroid gland lateral to the carotid artery and jugular vein, however, cannot be readily explained by current embryological information. In these instances, and especially for intranodal thyroid tissue, a metastasis from an occult thyroid primary is the mandatory first consideration. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors influencing reticulophagocytic function in insulin-treated diabetes.
The splenic component of reticulophagocytic function (RPF) was examined in 29 insulin-treated diabetic subjects (13 type I and 16 type II) by measurement of clearance of altered, radiolabeled, autologous erythrocytes. Double-isotope studies were performed with cells altered by: (1) preincubation with N-ethylmaleimide (NEM) and (2) coating with IgG antibody to the Rhesus (Rh) D antigen, labeled with 99mTc and 51Cr, respectively. HLA typing for the A, B, and DR loci was performed in those patients showing a defect in the clearance of IgG-coated cells. Values for half-life (t1/2) were correlated with the incidence of diabetic complications, levels of HbA1, and circulating immune complexes (CIC). Two patterns of abnormal clearance were observed: first, an isolated defect of IgG-coated cell clearance in 7 patients (3 had the HLA B8/DR3 haplotype) and second, abnormal removal of both types of cell in a further 7 patients (3 had B8/DR3). There was no correlation between half-lives as measured by the two methods, although exclusion of the patients with a defect of IgG-coated cell clearance alone yielded a highly significant correlation for the remaining 15 Rh-positive patients (P less than 0.01). Abnormalities of IgG-coated cell clearance were more frequent in patients with HbA1 greater than 9% (P less than 0.02), while t1/2 of NEM-altered cells was significantly greater in patients with CIC (P less than 0.05). There was no correlation between t1/2 and the incidence of peripheral complications.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering.
In order to induce the chondrogenesis of mesenchymal stem cells (MSCs) in tissue engineering, a variety of growth factors have been adapted and encouraging results have been demonstrated. In this study, we developed a delivery system for dual growth factors using a gelation rate controllable alginate solution (containing BMP-7) and polyion complex nanoparticles (containing TGF-beta(2)) to be applied for the chondrogenesis of MSCs. The dual growth factors (BMP-7/TGF-beta(2))-loaded nanoparticle/hydrogel system showed a controlled release of both growth factors: a faster release of BMP-7 and a slower release of TGF-beta(2), ca., approximately 80 and 30% release at the end of an incubation period (21 days), respectively, which may be highly desirable for chondrogenic differentiation of MSCs. On the contrary, the release of each growth factor from the dual growth factors-loaded hydrogel (without the nanoparticles) was much slower than that of the nanoparticle/hydrogel system, approximately 36% (BMP-7) and 16% (TGF-beta(2)) for 21 days, and this is more than likely attributed to the aggregation between growth factors during the hydrogel fabrication step. The nanoparticle/hydrogel system with separate growth factor loading may provide desirable growth factor delivery kinetics for cartilage regeneration, as well as the chondrogenesis of MSCs. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term care facility policies on life-sustaining treatments and advance directives in Canada.
To describe the prevalence and content of long-term care facility policies regarding the use of life-sustaining treatments (cardiopulmonary resuscitation (CPR), artificial hydration and nutrition, dialysis, antibiotics for life-threatening infections, transfer to acute care hospital) and advance directives in Canada. Cross-sectional mailed survey. Canadian long-term care facilities with 25 beds or more listed in the 1991-92 Directory of Long Term Care Centres in Canada. Institutions listed as, "general hospitals," "psychiatric hospitals," "children's treatment centres," "group homes," or as purely residential facilities were excluded. Chief Executive Officers or their designates. Respondents' self-reports regarding the existence of life-sustaining treatment or advance directive policies and content analysis of the policies themselves. Of 1472 long-term care facilities, 1021 (69%) responded. Of these, 344 (34%) institutions had 397 policies regarding the use of life-sustaining treatments or advance directives. Three hundred twenty facilities (31%) had 349 do-not-resuscitate (DNR) policies (40% on CPR alone and 60% on CPR plus other life-sustaining treatments). Seventeen institutions (2%) each had one policy addressing life-sustaining treatments other than CPR, and 31 institutions (3%) each had one policy addressing advance directives. Of the 397 policies, 171 (43%) required routine discussion with all patients, 156 (39%) mentioned futility, 331 (83%) indicated that the competent patient had the right to make a decision about life-sustaining treatment, 265 (67%) indicated that the family of the incompetent patient had this right, 27 policies (7%) mentioned conflict resolution, 378 (95%) had an explicit requirement for recording the decision, 10 (3%) required explicit communication of the decision to the competent patient, 10 (3%) required such communication to the family of the incompetent patient, 260 (66%) required updating of the decision, and 213 (54%) mentioned rescinding or changing the decision. Only one-third of Canadian long-term care facilities have do-not-resuscitate policies, and even fewer have policies on advance directives or life-sustaining treatments other than CPR. The policies themselves could be improved by encouraging routine advance discussions, scrutinizing the use of the futility standard, stipulating procedures for conflict resolution, and explicitly requiring communication of the decision to competent patients or substitute decision makers of incompetent patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolated collagenoma: a case report with a review of connective tissue nevi of the collagen type.
A 22-year-old male had had five skin colored tumorous growths on the mid-palm, ring and little fingers of the right hand for the last 15 years. Histopathological examination with hematoxylin and eosin and special stains confirmed the diagnosis of connective tissue nevi of collagen type. There were no associated cutaneous or systemic findings; thus the case was designated as isolated collagenoma. A review of connective tissue nevi of the collagen type is presented. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthetic regimes due to packing constraints in dendritic molecules confirmed by labelling experiments.
Classical theory predicts that branching defects are unavoidable in large dendritic molecules when steric congestion is important. Here we report first experimental evidence of this effect via labelling measurements of an extended homologous series of generations g = 1...6 of dendronized polymers. This system exhibits a single type of defect interrogated specifically by the Sanger reagent thus permitting to identify the predicted upturn in the number of branching defects when g approaches g(max) and the polymer density approaches close packing. The average number of junctions and defects for each member of the series is recursively obtained from the measured molar concentrations of bound labels and the mass concentrations of the dendritic molecules. The number of defects increases at g=5 and becomes significant at g=6 for dendronized polymers where the g(max) was estimated to occur at 6.1 ≤ g(max) ≤ 7.1. The combination of labelling measurements with the novel theoretical analysis affords a method for characterizing high g dendritic systems. | {
"pile_set_name": "PubMed Abstracts"
} |
Microbiologic changes during antimicrobial treatment and rate of relapse of distal respiratory tract infections in foals.
Despite the high incidence of distal respiratory tract infection of undetermined cause on farms, to our knowledge, the microbiologic effects of conventional antimicrobial treatment for this condition have not been studied. We evaluated the possible pathogenic role of bacterial isolates from the distal airways of foals with clinical respiratory tract disease, by correlating changes in their numbers (increase or decrease) with clinical, endoscopic, and pulmonary cytologic signs of disease resolution during treatment with antimicrobial drugs. We also determined qualitative changes in in vitro antimicrobial susceptibility of bacterial isolates after 7 days of treatment and relapse rate of foals. Significant (P < 0.05) decrease in the numbers of an isolate in the airways was considered strong evidence of a pathogenic role in this disease syndrome. Foals with endoscopically confirmed distal respiratory tract infection (DRTI; n = 65) were selected at random for treatment (n = 56) or nontreatment (n = 9), and bronchial lavage specimens were cultured and evaluated cytologically before and after 7 days of treatment with trimethoprim-sulfamethoxazole (TMS) and a beta-lactam drug (penicillin, ampicillin, or sulbactam-ampicillin), the standard treatment in all foals. The effect of treatment was to abruptly reduce the clinical (nasal discharge, cough, adventitious lung sounds) and cytologic signs of airway infection. Severity of disease in nontreated foals, however, did not change or did worsen over time. Reduction in the frequency and numbers of Streptococcus zooepidemicus isolated during treatment supported a causal role for this organism in the clinical syndrome observed.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Examining the Association Between Apparent Temperature and Mental Health-Related Emergency Room Visits in California.
The association between ambient temperature and morbidity has been explored previously. However, the association between temperature and mental health-related outcomes, including violence and self-harm, remains relatively unexamined. For the period 2005-2013, we obtained daily counts of mental health-related emergency room visits involving injuries with an external cause for 16 California climate zones from the California Office of Statewide Health Planning and Development and combined them with data on mean apparent temperature, a combination of temperature and humidity. Using Poisson regression models, we estimated climate zone-level associations and then used random-effects meta-analyses to produce overall estimates. Analyses were stratified by season (warm: May-October; cold: November-April), race/ethnicity, and age. During the warm season, a 10°F (5.6°C) increase in same-day mean apparent temperature was associated with 4.8% (95% confidence interval (CI): 3.6, 6.0), 5.8% (95% CI: 4.5, 7.1), and 7.9% (95% CI: 7.3, 8.4) increases in the risk of emergency room visits for mental health disorders, self-injury/suicide, and intentional injury/homicide, respectively. High temperatures during the cold season were also positively associated with these outcomes. Variations were observed by race/ethnicity, age group, and sex, with Hispanics, whites, persons aged 6-18 years, and females being at greatest risk for most outcomes. Increasing mean apparent temperature was found to have acute associations with mental health outcomes and intentional injuries, and these findings warrant further study in other locations. | {
"pile_set_name": "PubMed Abstracts"
} |
To the editor in reply to Dr. Crow's letter.
We are delighted that our discovery of autoantibodies directed against LINE-1 retroelement-encoded p40/ORF1p in SLE patients (1) has been so rapidly replicated and we thank Dr. Crow for her excellent summary of our findings. Her group's detection of LINE-1 mRNA and immunoreactive p40 protein in salivary gland biopsies from primary Sjögren's syndrome patients and in kidney biopsies from SLE patients (2) was an important impetus for our study. This article is protected by copyright. All rights reserved. | {
"pile_set_name": "PubMed Abstracts"
} |
On the diversity of insulin secretion and sensitivity in subjects with impaired glucose tolerance.
Insulin secretion and sensitivity are basic characteristics determining the glucose tolerance. The aim of this study was to investigate if derangements in these two main characteristics were generally found in subjects with impaired glucose tolerance (IGT). The early insulin response at the intravenous glucose tolerance test (IVGTT) in 42 subjects with IGT was found to be correlated to the glucose tolerance (r = -0.38, p < 0.01 vs, fasting glucose and r = 0.35, p < 0.02, vs the k-value of IVGTT) while fasting insulin was found to be closely correlated to insulin sensitivity, measured by the euglycemic clamp method (r = -0.83, p < 0.003, n = 11). Using data obtained at the IVGTT's in the IGT subjects, different patterns of insulin secretion were found representing different combinations of impairments in insulin secretion and sensitivity. However, in the majority of the IGT subjects a marked decrease in the early insulin response and a fasting hyperinsulinemia were found. The present study suggest such a characterization by the IVGTT to be of importance for a better understanding of the dynamic interplay between insulin secretion and sensitivity in IGT subjects. | {
"pile_set_name": "PubMed Abstracts"
} |
Diagnostic tests and information theory.
Our previous article showed that the discriminating properties of most diagnostic tests in medicine can be characterized by assuming that tests separate disordered and nondisordered individuals into two overlapping, normal distributions with different means and standard deviations. In this article, we explore the relationship between this way of describing diagnostic tests and the reason that clinicians use them: to gain information about their patients and to reduce diagnostic uncertainty. | {
"pile_set_name": "PubMed Abstracts"
} |
Childhood antecedents of personality disorder: an alternative perspective.
One of the fundamental limitations of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Text Revision (DSM-IV-TR) categorical model of personality disorder classification has been the lack of a strong scientific foundation, including an understanding of childhood antecedents. The DSM-IV-TR personality disorders, however, do appear to be well understood as maladaptive variants of the domains and facets of the general personality structure as conceptualized within the five-factor model (FFM). Integrating the classification of personality disorder with the FFM brings to an understanding of the personality disorders a considerable body of scientific research on childhood antecedents. The temperaments and traits of childhood do appear to be antecedent to the FFM of adult personality structure, and these temperament and traits of childhood and adolescence are the likely antecedents for adult personality disorder, providing further support for the conceptualization of the adult personality disorders as maladaptive variants of the domains and facets of the FFM. Conceptualizing personality disorders in terms of the FFM thereby provides a basis for integrating the classification of abnormal and normal personality functioning across the life span. | {
"pile_set_name": "PubMed Abstracts"
} |
Contrast-enhanced US-guided radiofrequency ablation of hepatocellular carcinoma.
Contrast-enhanced ultrasound (US) has been shown to be an efficient imaging modality in guiding radiofrequency (RF) ablation of hepatocellular carcinomas (HCC). The purpose of the present study was to assess the usefulness of contrast-enhanced US in guiding RF ablation in patients with early-stage HCC that was not clearly visible on grayscale US or noncontrast computed tomography (CT). During a 17-month period, contrast-enhanced US-guided RF ablation was performed in 14 patients with 19 early-stage lesions that were poorly defined on grayscale US and noncontrast CT. Contrast-enhanced US was repeated after 30 minutes, and complete ablation was defined as absence of any arterial-phase enhancement within the ablated lesion. Patients were followed periodically with clinical evaluation, liver function tests, α-fetoprotein measurement, and multiphasic CT or magnetic resonance (MR) imaging for a minimum of 1 year after ablation to look for local recurrence or disease progression. Survival probability was estimated with the Kaplan-Meier method. Complete tumor ablation was achieved in all 19 lesions, with no evidence of residual or recurrent tumor in the ablated areas after a mean follow-up of 16 months. No major complications were observed in any patient. However, new lesions developed in other parts of the liver on follow-up scans in three patients, and were accordingly treated with RF ablation. Two patients died of disease progression or liver failure within the 1-year follow-up. For early-stage HCCs not well visualized on unenhanced US or CT, contrast-enhanced US provides an additional tool to guide RF ablation. | {
"pile_set_name": "PubMed Abstracts"
} |
Antibiosis-type insect resistance in transgenic plants expressing a teratocyte secretory protein (TSP14) gene from a hymenopteran endoparasite (Microplitis croceipes).
We have isolated a teratocyte secretory protein (TSP14) gene product from a hymenopteran endoparasite that disrupts the growth of lepidopteran insect larvae. To evaluate the insecticidal activity of TSP14 for the protection of crops from insect damage, chimeric gene constructs of TSP14 were expressed in transgenic plants. The coding sequence of the TSP14 gene, with and without its native signal peptide, was placed between the modified peanut chlorotic streak virus (PClSV) full-length transcript (FLt) promoter with duplicated enhancer domains and the terminator sequence from the rbcSE9 gene. These chimeric genes, expressed in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) were stably inherited in successive plant generations (R0, R1 and R2 progeny) as shown by molecular analysis. A Western blot analysis of plant extracts showed the presence of a polypeptide of the expected size that cross-reacted with TSP14-specific antibodies. Larvae of the tobacco budworm (Heliothis virescens) and tobacco hornworm (Manduca sexta) which were fed with several independent homozygous transgenic plant lines (R2 progeny) exhibited mortality and reduced growth rates compared to those fed with plants transformed by a vector control. Our results demonstrate the potential for introduction of the TSP14 gene into plants in order to achieve protection against lepidopteran pests. | {
"pile_set_name": "PubMed Abstracts"
} |
Rhinolithiasis: review of 21 cases.
Rhinolithiasis is masses that result from the deposition of salts around an intranasal foreign body. Rhinoliths are rare and rhinolithiasis is generally reported in the literature in single case studies. This study presents 21 cases of rhinolithiasis with a large series of clinical findings, diagnosis, and treatment. A total of 21 patients diagnosed with rhinolithiasis were identified. Clinical presentations, signs, and symptoms of the patients with radiological findings are presented, and x-ray diffraction analyses of three of the removed rhinoliths were performed to assess their mineralogical composition. A total of 21 patients (9 male and 12 female patients; age range, 4-63 years) diagnosed with rhinolithiasis were reviewed in this study. The most common symptoms were noted as purulent rhinorrhea and nasal obstruction. The other symptoms were headache, oral malodor, and recurrent epistaxis. Nasal endoscopic examination was used for diagnosis of all patients. Endoscopic nasal examinations and computerized tomography (CT) findings revealed that rhinolithiasis was accompanied by sinusitis, chronic vestibulitis, allergic rhinitis, septum deviation, and squamous cell carcinoma. Rhinoliths were fully excised by using endoscopic nasal surgery. Mineralogical analyses of the three removed stones revealed dahllite [Ca(5)(PO(4),CO(3))(3)OH]. Cases of rhinolithiasis are seen rarely. It should always be considered in patients complaining from long-term unilateral nasal obstruction and unilateral purulent rhinorrhea. The treatment involves the removal of the rhinolith and the use of appropriate antibiotic therapy to control local infection. Rigid nasal endoscopy is the most important method to be used in diagnosis and treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Sun-induced chlorophyll fluorescence from high-resolution imaging spectroscopy data to quantify spatio-temporal patterns of photosynthetic function in crop canopies.
Passive detection of sun-induced chlorophyll fluorescence (SIF) using spectroscopy has been proposed as a proxy to quantify changes in photochemical efficiency at canopy level under natural light conditions. In this study, we explored the use of imaging spectroscopy to quantify spatio-temporal dynamics of SIF within crop canopies and its sensitivity to track patterns of photosynthetic activity originating from the interaction between vegetation structure and incoming radiation as well as variations in plant function. SIF was retrieved using the Fraunhofer Line Depth (FLD) principle from imaging spectroscopy data acquired at different time scales a few metres above several crop canopies growing under natural illumination. We report the first maps of canopy SIF in high spatial resolution. Changes of SIF were monitored at different time scales ranging from quick variations under induced stress conditions to seasonal dynamics. Natural changes were primarily determined by varying levels and distribution of photosynthetic active radiation (PAR). However, this relationship changed throughout the day demonstrating an additional physiological component modulating spatio-temporal patterns of SIF emission. We successfully used detailed SIF maps to track changes in the canopy's photochemical activity under field conditions, providing a new tool to evaluate complex patterns of photosynthesis within the canopy. | {
"pile_set_name": "PubMed Abstracts"
} |
The effects of concentration-dependent morphology of self-assembling RADA16 nanoscaffolds on mixed retinal cultures.
RADA16 self-assembling peptide nanofiber scaffolds (SAPNSs) have been shown to have positive effects on neural regeneration following injury to the central nervous system in vivo, but mechanisms are unclear. Here we show that RADA16 SAPNSs form scaffolds of increasing fiber density with increasing peptide concentration which in turn has a concentration-dependent effect on neurons and astrocytes in mixed retinal cultures. Importantly, we report that the final nanoscale fiber architecture is an important factor to consider in designing scaffolds to promote regeneration in the central nervous system. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical and economic evaluation of the Trellis-8 infusion catheter for deep vein thrombosis.
To summarize the preliminary experience with the Trellis-8 infusion catheter (TIC) in the treatment of deep venous thrombosis (DVT) and compare the outcome to that with catheter-directed thrombolysis (CDT) by using a meta-analysis of published reports. Technical success, bleeding complications, and costs for patients treated with the TIC for DVT were reported through a voluntary, company-sponsored registry. Technical success was classified by using the National Venous Registry grading scale for DVT lysis (<50% lysis = grade I, 50%-99% lysis = grade II, and 100% lysis = grade III). The cost of treatment with the TIC was based on equipment (catheters) needed to perform the intervention, thrombolytic agents used, bleeding episodes, procedure time in the angiography and/or interventional suite, and monitoring time in a critical care unit. Outcomes with the TIC were compared against outcomes with CDT by using literature-derived outcomes derived from a meta-analysis. Thrombolytic doses and infusion durations were less with TIC than with conventional CDT. Grade II and III lysis was achieved in 93% of patients treated with the TIC and 79% of patients treated with CDT (P = .03). Major hemorrhage was reported in none of the TIC patients and in 8.5% of patients treated with CDT (P < .001). The per-patient cost of therapy was $3,697 for TIC and $5,473 for CDT (P = .03). Thrombolysis in DVT with the TIC is associated with a greater technical success rate, a lower rate of bleeding, and a lower cost than that reported for CDT. These preliminary results indicate that further evaluation of the TIC in the treatment of DVT is warranted. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical guides to preventing ethical conflicts between pregnant women and their physicians.
We provide a justification for preventive ethics in obstetric practice. Four clinical guides to resolving ethical conflicts between pregnant women and their physicians can be identified: (1) informed consent as an ongoing dialogue between the pregnant woman and her physician, (2) negotiation as a clinical strategy, (3) respectful persuasion as a clinical strategy, and (4) the proper use of ethics committees. | {
"pile_set_name": "PubMed Abstracts"
} |
Activation of potassium and chloride channels by tumor necrosis factor alpha. Role in liver cell death.
Despite abundant evidence for changes in mitochondrial membrane permeability in tumor necrosis factor (TNF)-mediated cell death, the role of plasma membrane ion channels in this process remains unclear. These studies examine the influence of TNF on ion channel opening and death in a model rat liver cell line (HTC). TNF (25 ng/ml) elicited a 2- and 5-fold increase in K(+) and Cl(-) currents, respectively, in HTC cells. These increases occurred within 5-10 min after TNF exposure and were inhibited either by K(+) or Cl(-) substitution or by K(+) channel blockers (Ba(2+), quinine, 0.1 mm each) or Cl(-) channel blockers (10 microm 5-nitro-2-(3-phenylpropylamino)benzoic acid and 0.1 mm N-phenylanthranilic acid), respectively. TNF-mediated increases in K(+) and Cl(-) currents were each inhibited by intracellular Ca(2+) chelation (5 mm EGTA), ATP depletion (4 units/ml apyrase), and the protein kinase C (PKC) inhibitors chelerythrine (10 micrometer) or PKC 19-36 peptide (1 micrometer). In contrast, currents were not attenuated by the calmodulin kinase II 281-309 peptide (10 micrometer), an inhibitor of calmodulin kinase II. In the presence of actinomycin D (1 micrometer), each of the above ion channel blockers significantly delayed the progression to TNF-mediated cell death. Collectively, these data suggest that activation of K(+) and Cl(-) channels is an early response to TNF signaling and that channel opening is Ca(2+)- and PKC-dependent. Our findings further suggest that K(+) and Cl(-) channels participate in pathways leading to TNF-mediated cell death and thus represent potential therapeutic targets to attenuate liver injury from TNF. | {
"pile_set_name": "PubMed Abstracts"
} |
The many postures of noncanonical Wnt signaling in development and diseases.
Wnt signaling regulates many aspects of vertebrate development. Its dysregulation causes developmental defects and diseases including cancer. The signaling can be categorized in two pathways: canonical and noncanonical. Canonical pathway plays a key role in regulating proliferation and differentiation of cells whilst noncanonical Wnt signaling mainly controls cellular polarity and motility. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that noncanonical Wnt signaling is involved in adult tissue development and cancer progression. In this review, we try to describe and discuss the mechanisms behind the biological effects of noncanonical Wnt signaling, diseases caused by its dysregulation, and implications in adult tissue development biology. | {
"pile_set_name": "PubMed Abstracts"
} |
DWI filtering using joint information for DTI and HARDI.
The filtering of the Diffusion Weighted Images (DWI) prior to the estimation of the diffusion tensor or other fiber Orientation Distribution Functions (ODF) has been proved to be of paramount importance in the recent literature. More precisely, it has been evidenced that the estimation of the diffusion tensor without a previous filtering stage induces errors which cannot be recovered by further regularization of the tensor field. A number of approaches have been intended to overcome this problem, most of them based on the restoration of each DWI gradient image separately. In this paper we propose a methodology to take advantage of the joint information in the DWI volumes, i.e., the sum of the information given by all DWI channels plus the correlations between them. This way, all the gradient images are filtered together exploiting the first and second order information they share. We adapt this methodology to two filters, namely the Linear Minimum Mean Squared Error (LMMSE) and the Unbiased Non-Local Means (UNLM). These new filters are tested over a wide variety of synthetic and real data showing the convenience of the new approach, especially for High Angular Resolution Diffusion Imaging (HARDI). Among the techniques presented, the joint LMMSE is proved a very attractive approach, since it shows an accuracy similar to UNLM (or even better in some situations) with a much lighter computational load. | {
"pile_set_name": "PubMed Abstracts"
} |
[Diagnosis of interstitial cystitis].
Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects. | {
"pile_set_name": "PubMed Abstracts"
} |
New nucleoside-5'-alkylphosphonophosphates and related compounds containing 2'-deoxycytidine, thymidine and adenosine as nucleoside component. Syntheses and their effects on tumor cell growth in vitro.
Recent studies have shown that phosphono analogs of cytidine-5'-diphosphate diacylglycerol (CDP-DAG) possessing a structurally modified lipid moiety exhibit antiproliferative activity in vitro. As an extension of our previous work we tried to elucidate whether the presence of the cytidine component is necessary for cytostatic activity. In this context we have synthesized similarly structured nucleoside-phospholipid conjugates containing nucleoside components other than cytidine, which also do not exhibit cytostatic properties as such. The compounds include 5'-alkyldiphosphates and 5'-alkylphosphonophosphates of 2'-deoxycytidine, thymidine and adenosine with different alkyl chain length as well as selected 3-hexadecyl-2-chloro-2-deoxyglycero-(1)-diphosphates and -phosphonophosphates of these nucleosides. The chemical structures of the newly synthesized nucleoside-phospholipid conjugates were confirmed by fast atom bombardment (FAB) and electrospray ionization (ESI) mass spectrometry. It was found that these compounds also inhibit the cell growth of different human cell lines, i.e. the presence of the cytidine component is not a necessary prerequisite for the antiproliferative activity of these nucleoside-phospholipid conjugates. | {
"pile_set_name": "PubMed Abstracts"
} |
[Equine motor neuron disease: a review based on a case report].
A 10-year-old, non-pregnant Dutch Warmblood mare was referred to the Department of Equine Science because of chronic weight loss, despite good appetite, and dullness. Clinical examination revealed muscle atrophy, trembling of the limb muscles, an abnormal stance in which all four limbs were placed under the body, and an abnormal low head carriage. The plasma vitamin E concentration was markedly decreased (0.2 mumol/l), the electromyographic (EMG) examination was consistent with denervation, and the oral glucose absorption test was below the reference value (40% increase over the resting glucose level). Because of the clinical diagnosis of equine motor neuron disease (EMND), the horse was euthanazed and post-mortem examination confirmed this diagnosis. Based on the similarity in pathological findings, EMND can be compared to amyotrophic lateral sclerosis (ALS) in humans. However, in horses, only the lower motor neurons and occasionally some nuclei of the cranial nerves are affected. Because of the low plasma vitamin E concentration found in horses with EMND, an absolute or a relative antioxidant deficiency can be involved in the pathogenesis. In general, it is a progressive disease process and stabilization of the situation is the best feasible result. There is no specific therapy other than vitamin E supplementation and the prognosis is poor. | {
"pile_set_name": "PubMed Abstracts"
} |
Risk of recurrence of fetal chromosomal aberrations: analysis of trisomy 21, trisomy 18, trisomy 13, and 45,X in 1,076 Japanese mothers.
To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. This collaborative study consisted of 1,076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1,248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45,X offspring, 1 with mos 45,X/46,XX had another such fetus. The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45,X should be examined for mos 45,X/46,XX. | {
"pile_set_name": "PubMed Abstracts"
} |
Reassessing the impact of cytomegalovirus infection in kidney and kidney-pancreas transplantation.
New antiviral agents and practice guidelines have been implemented to address cytomegalovirus (CMV) infection in organ transplantation. We hypothesized that such measures would reduce rates of symptomatic CMV infection, CMV disease, and CMV seroconversion and associated complications in renal transplant and simultaneous pancreas-kidney transplant recipients. We analyzed the impact of CMV in 1,424 renal transplant and simultaneous pancreas-kidney transplant recipients, transplanted at our center between January 1, 1994 and June 30, 1999. Most patients received quadruple sequential immunosuppression with high-dose acyclovir (800 mg four times daily) for 12 weeks as prophylaxis. High-risk patients (donor CMV-positive/recipient CMV-negative) received ganciclovir (500 to 1,000 mg three times daily) beginning in 1998, again for 12 weeks. One hundred and one renal transplant (9.0%) and 40 simultaneous pancreas-kidney transplant (13.4%) recipients experienced symptomatic CMV infection or CMV disease. Donor CMV-positive/recipient CMV-negative patients had the greatest rates of CMV infection or CMV disease (25.2%; P = 0.0001 versus all other categories). The impact of CMV on outcomes was evaluated in a proportional hazards model. Symptomatic CMV infection or CMV disease increased the risk for subsequent rejection (relative risk, 2.11; P = 0.003) and non-CMV infection (relative risk, 2.24; P = 0.001). To determine if the effects of ganciclovir were masked by pre-1998 data, CMV infection and CMV disease rates for ganciclovir-treated patients (n = 62) were censored at 1 year and compared with acyclovir-treated patients (n = 287). Ganciclovir was associated with trends toward lower rates of infection and disease. It also delayed the time to infection or disease. Serologic testing in high-risk patients also showed late seroconversion, with 20% of patients seroconverting by 6 months, 12 weeks after the prophylaxis period. These data suggest that despite better prophylaxis strategies, CMV remains an important pathogen in renal transplant and simultaneous pancreas-kidney transplant recipients. This finding may require reassessment of prophylaxis strategies and the development of alternative or novel anti-CMV regimens. | {
"pile_set_name": "PubMed Abstracts"
} |
Making the invisible body visible. Bone scans, osteoporosis and women's bodily experiences.
The imaging technology of bone scans allows visualization of the bone structure, and determination of a numerical value. Both these are subjected to professional interpretation according to medical (epidemiological) evidence to estimate the individual's risk of fractures. But when bodily experience is challenged by a visual diagnosis, what effect does this have on an individual? The aim of this study was to explore women's bodily experiences after a bone scan and to analyse how the scan affects women's self-awareness, sense of bodily identity and integrity. We interviewed 16 Danish women (aged 61-63) who had had a bone scan for osteoporosis. The analysis was based on Merleau-Ponty's perspective of perception as an embodied experience in which bodily experience is understood to be the existential ground of culture and self. Women appeared to take the scan literally and planned their lives accordingly. They appeared to believe that the 'pictures' revealed some truth in themselves. The information supplied by the scan fostered a new body image. The women interpreted the scan result (a mark on a curve) to mean bodily fragility which they incorporated into their bodily perception. The embodiment of this new body image produced new symptom interpretations and preventive actions, including caution. The result of the bone scan and its cultural interpretation triggered a reconstruction of the body self as weak with reduced capacity. Women's interpretation of the bone scan reorganized their lived space and time, and their relations with others and themselves. Technological information about osteoporosis appeared to leave most affected women more uncertain and restricted rather than empowered. The findings raise some fundamental questions concerning the use of medical technology for the prevention of asymptomatic disorders. | {
"pile_set_name": "PubMed Abstracts"
} |
Model-based advanced process control of coagulation.
The drinking water treatment industry has seen a recent increase in the use of artificial neural networks (ANNs) for process modelling and offline process control tools and applications. While conceptual frameworks for integrating the ANN technology into the real-time control of complex treatment processes have been proposed, actual working systems have yet to be developed. This paper presents development and application of an ANN model-based advanced process control system for the coagulation process at a pilot-scale water treatment facility in Edmonton, Alberta, Canada. The system was successfully used to maintain a user-defined set point for effluent quality, by automatically varying operating conditions in response to changes in influent water quality. This new technology has the potential to realize significant operational cost saving for utilities when applied in full-scale applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Critical incident reporting in the intensive care unit.
Critical incident reporting was introduced into the intensive care unit (ICU) as part of the development of a quality assurance programme within our department. Over a 3-year period 281 critical incidents were reported. Factors relating to causation, detection and prevention of critical incidents were sought. Detection of a critical incident in over 50% of cases resulted from direct observation of the patient while monitoring systems accounted for a further 27%. No physiological changes were observed in 54% of critical incidents. The most common incidents reported concerned airway management and invasive lines, tubes and drains. Human error was a factor in 55% of incidents while violations of standard practice contributed to 28%. Critical incident reporting was effective in revealing latent errors in our "system' and clarifying the role of human error in the generation of incidents. It has proven to be a useful technique to highlight problems previously undetected in our quality assurance programme. Improvements in quality of care following implementation of preventative strategies await further assessment. | {
"pile_set_name": "PubMed Abstracts"
} |
Cognitive approaches to summary measurement: its application to the measurement of diversity in health-related quality of life assessments.
This paper describes elements of a cognitive approach to summary measurement, as it is applied to health-related quality of life (HRQOL) assessment. A summary measure, by its very nature, represents, but does not reproduce, some body of information. As a consequence, how a summary measure is formulated becomes a critical determinant of its usefulness. In most cases, formal (arithmetic or investigator-based) methods are used. However, it was also noted that a person ordinarily summarizes the information they receive. Qualitative analytic techniques (e.g., cognitive interviewing methods) can provide insight into the cognitive processes underlying such summary formation. These cognitive processes, formulated as algorithms, would also be expected to vary as a function of different groups of respondents and settings. Finding a common denominator, a common algorithm, would provide a consensus summary measure amongst diverse groups whose HRQOL is being assessed. | {
"pile_set_name": "PubMed Abstracts"
} |
Pathophysiology of vascular dementia and white matter changes.
Vascular dementia (VaD) can be defined as a dementia syndrome likely to be the consequence of lesions of the brain, vascular in origin, irrespective of their ischemic, hemorrhagic or hypoxic nature. Six subtypes (1) multi-infarct dementia, (2) strategic single infarct dementia, (3) small-vessel disease with dementia, (4) hypoperfusion dementia, (5) hemorrhagic dementia and other VaD, have been proposed, indicating the broad clinical spectrum of this disorder. Major determinants of the dementia syndrome are (i) stroke characteristics--i.e., lacunar infarcts, localization in the left hemisphere and/or in strategic regions--, (ii) white matter changes frequently seen in stroke patients, especially in those who have lacunes or deep hemorrhages, represent a strong predictor for risk of dementia--and (iii) associated Alzheimer pathology--Alzheimer and vascular lesions are frequently associated. Finally, it should also be considered the role of the summation of various lesion types, since many cases of dementia occurring in stroke patients are multifactorial. | {
"pile_set_name": "PubMed Abstracts"
} |
A case-control study of lung cancer in nonsmoking women.
A case-control study of Japanese women in Nagoya was conducted to investigate the significance of passive smoking and other factors in relation to the etiology of female lung cancer. A total of 90 nonsmoking patients with primary lung cancer and their age- and hospital-matched female controls were asked to fill in a questionnaire in the hospital. Elevated relative risk (RR) of lung cancer was observed for passive smoking from mother (RR = 4.0; p less than 0.05) and from husband's father (RR = 3.2; p less than 0.05). No association was observed between the risk of lung cancer and smoking of husband or passive smoke exposure at work. Occupational exposure to iron or other metals also showed high risk (RR = 4.8; p less than 0.05). No appreciable differences in food intakes were observed between cases and controls. | {
"pile_set_name": "PubMed Abstracts"
} |
Fabrication of a hybrid PDMS/SU-8/quartz microfluidic chip for enhancing UV absorption whole-channel imaging detection sensitivity and application for isoelectric focusing of proteins.
A poly(dimethylsiloxane)(PDMS)/SU-8/quartz hybrid chip was developed and applied in the isoelectric focusing (IEF) of proteins with ultraviolet (UV) absorbance-based whole-channel imaging detection (UV-WCID). Each hybrid chip was made of three layers: a PDMS flat top substrate, a bottom quartz substrate and a middle layer of SU-8 photoresist. The SU-8 serves two purposes: it contains the microchannel used for IEF separation, and acts as an optical slit that absorbs UV light below 300 nm improving detection sensitivity in WCID. The novel hybrid design demonstrates a two to three times improvement in sensitivity over a comparable PDMS/PDMS design. In addition, the hybrid chip exhibits increased heat dissipation due to the superior thermal conductivity of the bottom quartz substrate allowing for larger electric fields to be used in separations. The hybrid design with IEF-UV-WCID was successful in resolving a complicated sample, hemoglobin control, with high fidelity. | {
"pile_set_name": "PubMed Abstracts"
} |
Sports for the physically disabled. The 1976 Olympiad (Toronto).
The 1976 Olympiad for the Physically Disabled was the first olympiad with full competition for blind, paralyzed, and amputee athletes. More than 1,500 from 38 countries took part in wheelchair (12 events), blind (8 events), and amputee (11 events) games. Participants were classified by an international team of doctors. The athletes were accomodated in university residences with small infirmaries. A school near the games site was used as a field hospital. Rest areas were also set up. Volunteers served on the medical staff (three doctors, three nurses, three receptionists, and three physical therapists on each of two shifts per day). In addition doctors, nurses, trainers, and physical therapists rotated around various venues at the games site. Physicians treated 285 patients (184 were athletes; others were spectators) for a variety of problems, physical therapists treated 119 athletes, and trainers treated 114 athletes. Contigency plans in case of mass disaster were made but were not needed. Disabled athletes are slightly more vulnerable to stress and fatigue than able-bodied athletes. The Toronto games will probably be remembered as the turning point in the emergence of sports for the disabled from a purely rehabilitation measure to a true sporting event in its own right. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparison of the bactericidal activity of 'Phoraid 6000' and 'Clearsol' disinfectants.
The bactericidal activity of 'Phoraid 6000' and 'Clearsol' disinfectants was evaluated using suspension and surface tests. In suspension tests, 2% 'Phoraid' achieved a > 5 log10 reduction of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus in 1 min in the absence of blood, but negligible activity in 10 min in the presence of 1% blood; 10% 'Phoraid' exhibited no useful activity in the presence of 5% blood and 20% Phoraid no useful activity in the presence of 10% blood. In contrast, 'Clearsol' was very resistant to neutralization by blood: 1% 'Clearsol' achieved a > 5 log10 reduction of P. aeruginosa, E. coli and S. aureus in 5 min in the presence of > or = 70% blood. In surface tests, undiluted 'Phoraid 6000' failed to disinfect wet blood contaminated with either P. aeruginosa, E. coli or Proteus vulgaris in the 2-min exposure period. 'Clearsol' gave mixed results: 2% 'Clearsol' was very effective but the standard use-dilution of 1% proved inadequate. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of a low-budget tobacco prevention media campaign.
Utah joined the ranks of other states that have passed a tobacco tax to fund a tobacco control program, including a media campaign. However, unlike other states working with multimillion dollar campaigns, $250,000 was allocated toward an anti-tobacco media campaign. Formative research guided the strategic development of the media campaign. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficient catalytic conversion of concentrated cellulose feeds to hexitols with heteropoly acids and Ru on carbon.
A combination of heteropolyacids and Ru on carbon catalyzes the conversion of concentrated cellulose feeds into hexitols under H(2) pressure. Quantitative conversion of ball-milled cellulose was observed with remarkable hexitol volume productivity. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of food restriction on life span and immune functions in long-lived Fischer-344 x Brown Norway F1 rats.
Life-long food restriction is known to slow aging and reduce the rate of occurrence of age-associated disease processes, but the mechanism by which this is accomplished is unknown. In this study we have examined the effect of food restriction on the proliferative response of spleen cells to mitogens and lymphokine production in 6-, 18-, and 30-month-old AL and FR Fischer-344 x Brown Norway (F-344 x BNF1) female rats whose average life span is 137 weeks on an ad libitum (AL) diet and 177 weeks on a food-restricted (FR) diet. In addition, the ability of food restriction to recall antigens was tested in 10-month-old rats by immunizing them with keyhole limpet and hen's egg albumin and measuring proliferative response of draining lymph node cells to these antigens. Our results indicated that the spleen-cell proliferative response to phytohemagglutinin and concanavalin A (Con A) was equal in 6- and 18-month-old rats but declined significantly in 30-month-old AL rats compared to FR rats. Although flow cytometric analyses did not reveal differences for CD4, CD8, and Ig+ cells with age, a significant rise in memory T cells (Ox-22low) in both CD4+ and CD8+ T-cell subset lineage was noted in AL-fed rats at 30 months of age. In FR rats, however, only a minimal shift of naive T cells (Ox-22high) to memory cells was observed. In FR rats, the observed changes in the naive and memory T-cell subsets correlate well with the observed higher levels of the antiinflammatory interleukin-2 (IL-2) and lower levels of the proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha. The ability of food-restricted animals to recall antigens was lower compared to their age-matched controls, though the proliferative response to T-cell mitogen Con A and superantigen staphylococcal enterotoxin B was higher. These findings indicate that food restriction may selectively act to maintain a lower number of antigen-induced memory T cells with age, thereby maintaining the organism's ability to produce higher levels of IL-2 with age. In summary, the increased cell-mediated immune function noted in aged FR rats appears to be due to the presence of a higher number of naive T cells, which are known to produce elevated levels of the antiinflammatory cytokines, which may in part be responsible for reducing the observed age-related rise in disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Differential mechanism of peptide YY and neuropeptide Y in inhibiting motility of guinea-pig colon.
The effect of peptide YY on contractility, acetylcholine release and noradrenaline release was examined in the isolated guinea-pig colon, and findings were compared with those for neuropeptide Y. Peptide YY and neuropeptide Y inhibited the twitch contractions mediated by the stimulation of cholinergic neurons. Peptide YY, neuropeptide Y, [Leu31,Pro34]neuropeptide Y and neuropeptide Y-(13-36) inhibited the electrically stimulated release of acetylcholine. Neuropeptide Y, but not peptide YY, inhibited the high K(+)-stimulated tetrodotoxin-resistant release of acetylcholine, while the inhibitory effect of neuropeptide Y disappeared after treatment with yohimbine. Neuropeptide Y, but not peptide YY or neuropeptide Y analogues, evoked the release of noradrenaline. After desensitization to the effects of neuropeptide Y, peptide YY inhibited electrically stimulated acetylcholine release. Thus, peptide YY inhibits acetylcholine release through stimulation of a receptor, distinct from the site of action of neuropeptide Y, located on cholinergic neurons as well as the neuropeptide Y Y1 and Y2 receptors in the guinea-pig colon. Neuropeptide Y inhibits acetylcholine release due to the noradrenaline release mediated by stimulation of a receptor distinct from neuropeptide Y Y1 and Y2 receptors, located on adrenergic neurons. | {
"pile_set_name": "PubMed Abstracts"
} |
Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.
Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets. | {
"pile_set_name": "PubMed Abstracts"
} |
Spatio-temporal cortical source imaging of brain electrical activity by means of time-varying parametric projection filter.
In the present study, we explore suitable spatio-temporal filters for inverse estimation of an equivalent dipole-layer distribution from the scalp electroencephalogram (EEG) for imaging of brain electric sources. We propose a time-varying parametric projection filter (tPPF) for the spatio-temporal EEG analysis. The performance of this tPPF algorithm was evaluated by computer simulation studies. An inhomogeneous three-concentric-spheres model was used in the present simulation study to represent the head volume conductor. An equivalent dipole layer was used to represent equivalently brain electric sources and estimated from the scalp potentials. The tPPF filter was tested to remove time-varying noise such as instantaneous artifacts caused by eyes-blink. The present simulation results indicate that the proposed time-variant tPPF method provides enhanced performance in rejecting time-varying noise, as compared with the time-invariant parametric projection filter. | {
"pile_set_name": "PubMed Abstracts"
} |
Human gut microbiota and its relationship to health and disease.
Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors associated with the specific worries of childhood cancer survivors: Cross-sectional survey in Japan.
Previous research has shown that adult childhood cancer survivors (CCS) have many worries. We re-analyzed the employment data in order to identify these worries and their associated factors. The participants were selected from the membership directory of Heart Link mutual-aid health insurance, and recruited by the CCS Network. We conducted a cross-sectional survey (a self-rated questionnaire on employment) via post or email with a link to an Internet website. We investigated the association between CCS factors and the specific worries. The adjusted odds ratios (OR) for the associated factors with a specific worry were estimated on logistic regression analysis. A total of 240 questionnaires were collected by November 2012. One questionnaire was excluded because the answers were not provided by the CCS him/herself. The most common worries were health-related problems (50%) and employment issues (40%), which were followed by his/her personality and life (23%) and self-appearance (20%). Fifty (21%) out of 239 CCS answered no specific worry. The common consistent factor associated with worries was the presence of late effects. Of note was that the CCS worries were not associated with age at diagnosis or follow up, gender, educational achievement or marriage. The worry about employment issues was associated with economic status, disability qualification, and employment status. The CCS worries were strongly affected by the presence of late effects. No significant association was noted between CCS worries and gender, age at diagnosis or follow up, or educational achievements. Economic status and disability qualification were associated with some worries. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasmodium falciparum incidence relative to entomologic inoculation rates at a site proposed for testing malaria vaccines in western Kenya.
Relationships between Plasmodium falciparum incidence and entomologic inoculation rates (EIRs) were determined for a 21-month period in Saradidi, western Kenya, in preparation for malaria vaccine field trials. Children, ranging in age from six months to six years and treated to clear malaria parasites, were monitored daily for up to 12 weeks to detect new malaria infections. Overall, new P. falciparum infections were detected in 77% of 809 children. The percentage of children that developed infections per two-week period averaged 34.7%, ranging from 7.3% to 90.9%. Transmission by vector populations was detected in 86.4% (38 of 44) of the two-week periods, with daily EIRs averaging 0.75 infective bites per person. Periods of intense transmission during April to August, and from November to January, coincided with seasonal rains. Relationships between daily malaria attack rates and EIRs indicated that an average of only 7.5% (1 in 13) of the sporozoite inoculations produced new infections in children. Regression analysis demonstrated that EIRs accounted for 74% of the variation in attack rates. One of the components of the EIR, the human-biting rate, alone accounted for 68% of the variation in attack rates. Thus, measurements of either the EIR or the human-biting rate can be used to predict corresponding attack rates in children. These baseline epidemiologic studies indicate that the intense transmission patterns of P. falciparum in Saradidi will provide excellent conditions for evaluating malaria vaccine efficacy. | {
"pile_set_name": "PubMed Abstracts"
} |
Thallium isotopic evidence for ferromanganese sediments in the mantle source of Hawaiian basalts.
Ocean island basalts are generally thought to be the surface expression of mantle plumes, but the nature of the components in the source regions of such mantle plumes is a subject of long-standing debate. The lavas erupted at Hawaii have attracted particular attention, as it has been proposed that coupled 186Os and 187Os anomalies reflect interaction with the Earth's metallic core. It has recently been suggested, however, that such variations could also result from addition of oceanic ferromanganese sediments to the mantle source of these lavas. Here we show that Hawaiian picrites with osmium isotope anomalies also exhibit pronounced thallium isotope variations, which are coupled with caesium/thallium ratios that extend to values much lower than commonly observed for mantle-derived rocks. This correlation cannot be created by admixing of core material, and is best explained by the addition of ferromanganese sediments into the Hawaii mantle source region. However, the lack of correlation between thallium and osmium isotopes and the high thallium/osmium ratios of ferromanganese sediments preclude a sedimentary origin for the osmium isotope anomalies, and leaves core-mantle interaction as a viable explanation for the osmium isotope variations of the Hawaiian picrites. | {
"pile_set_name": "PubMed Abstracts"
} |
Pre-steady-state kinetic analysis of 2-hydroxy-6-keto-nona-2,4-diene-1,9-dioic acid 5,6-hydrolase: kinetic evidence for enol/keto tautomerization.
The reaction catalyzed by 2-hydroxy-6-keto-nona-2,4-diene-1,9-dioic acid 5,6-hydrolase (MhpC) was analyzed by stopped-flow UV-visible kinetics at 317 nm (substrate depletion) and 270 nm (product formation) at pH 5.0 and 4.0. Comparison of the rates and amplitudes of product formation versus substrate depletion provided evidence for the formation of a discrete keto-intermediate, as predicted from previous isotope exchange experiments [Lam, W. W. Y., & Bugg, T. D. H. (1997) Biochemistry, 36, 12242-12251]. Accurate modeling of the concentration data could only be achieved using a branched kinetic mechanism in which the intermediate is released at a rate comparable to its catalytic turnover, consistent with the earlier isotope exchange data. The apparent "leakiness" of the active site and relatively weak substrate binding (Kd = 30 microM) are consistent with a mechanism in which the enzyme binds the dienol substrate in a strained, nonplanar conformation which promotes ketonization in the C-5 position to give a keto-intermediate. | {
"pile_set_name": "PubMed Abstracts"
} |
[Value of serum miR-155-5p and miR-133a-3p expression for the diagnosis and prognosis evaluation of sepsis].
To explore the value of serum microRNA-155-5p and -133a-3p (miR-155-5p and miR-133a-3p) expression for the diagnosis and prognosis evaluation of sepsis. A prospective observational study was conducted. 105 sepsis patients admitted to emergency intensive care unit (EICU) of the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2016 were enrolled. They were divided into three groups according to the severity: 35 patients with sepsis, 35 with severe sepsis, and 35 with septic shock. At the same time, 35 healthy persons were selected as the control group. According to the prognosis, the patients were divided into improved group (n = 70) and in-hospital death group (n = 35). The clinical data of all the subjects were collected. The mRNA expressions of miR-155-5p and miR-133a-3p were determined by reverse transcription-polymerase chain reaction (RT-PCR). The receiver-operating characteristic curve (ROC) was plotted to evaluate their clinical value for the diagnosis and prognosis of sepsis. The binary logistic regression was used to analyze the risk factors affecting the prognosis of sepsis patients. (1) The mRNA expressions of serum miR-155-5p and miR-133a-3p were gradually increased with the aggravation of sepsis. The mRNA expression of miR-155-5p (2-ΔCt) in sepsis, severe sepsis, sepsis shock groups was 1.89±0.48, 2.21±0.41, 2.79±0.73 (F = 23.737, P = 0.000), and the mRNA expression of miR-133a-3p (2(-ΔCt)) was 1.38±0.31, 1.74±0.65, 2.08±0.47, respectively (F = 27.710, P = 0.000). It was shown by ROC curve analysis that the area under the ROC curve (AUC) of serum miR-155-5p and miR-133a-3p for the diagnosis of sepsis was 0.855 [95% confidence interval (95%CI) = 0.761-0.949] and 0.769 (95%CI = 0.666-0.872) respectively. The cut-off value of miR-155-5p for the diagnosis of sepsis was 1.64, the sensitivity was 85.3%, and specificity was 80.6%. While the cut-off value of miR-133a-3p was 0.82, the sensitivity and specificity were 97.9% and 54.8% respectively. (2) Compared with improved group, the patients of in-hospital death group were more serious, and procalcitonin (PCT), C-reactive protein (CRP), D-dimer, lactic acid (Lac), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and the mRNA expressions of miR-155-5p and miR-133a-3p were significantly increased (all P < 0.05). While there was no statistically significant difference in gender, age, white blood cells (WBC), serum creatinine (SCr) between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that Lac [odds ratio (OR) = 0.514, 95%CI = 0.260-0.893, P = 0.024], sepsis severity (OR = 0.039, 95%CI = 0.023-2.955, P = 0.016), SOFA score (OR = 0.668, 95%CI = 0.474-0.825, P = 0.001), serum miR-155-5p expression (OR = 0.117, 95%CI = 0.020-0.530, P = 0.007) were the risk factors affecting the prognosis of patients with sepsis. The expression of serum miR-155-5p and miR-133a-3p may be used as specific indicators for the diagnosis of sepsis. And the expression of miR-155-5p can be used as independent impact factor for the estimation of sepsis prognosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Further understanding of the immunopathology of multiple sclerosis: impact on future treatments.
The understanding of the immunopathogenesis of multiple sclerosis (MS) has expanded with more research into T-cell subtypes, cytokine contributors, B-cell participation, mitochondrial dysfunction, and more. Treatment options have rapidly expanded with three relatively recent oral therapy alternatives entering the arena. In the following review, we discuss current mechanisms of immune dysregulation in MS, how they relate to current treatments, and the impact these findings will have on the future of therapy. Expert commentary: The efficacy of these medications and understanding their mechanisms of actions validates the immunopathogenic mechanisms thought to underlie MS. Further research has exposed new targets, while new promising therapies have shed light on new aspects into the pathophysiology of MS. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasmon hybridization in nanoshell dimers.
We extend the plasmon hybridization method to investigate the plasmon modes of metallic nanoshell dimers. The formalism is also generalized to include the effects of dielectric backgrounds. It is shown that the presence of dielectrics shifts the plasmon resonances of the individual nanoparticles to lower energies and screens their interaction in the dimer configuration. The net result is a redshift of dimer energies compared to the system without dielectrics and a weaker dependence of the dimer plasmon energies on dimer separation. We calculate the plasmon energies and optical absorption of nanoshell dimers as a function of dimer separation. The results are in excellent agreement with the results of finite difference time domain simulations. | {
"pile_set_name": "PubMed Abstracts"
} |
Current and emerging pharmaceutical interventions for myopia.
Myopia is a major cause of visual impairment. Its prevalence is growing steadily, especially in East Asia. Despite the immense disease and economic burden, there are currently no Food and Drug Administration-approved drugs for myopia. This review aims to summarise pharmaceutical interventions of myopia at clinical and preclinical stages in the last decade and discuss challenges for preclinical myopia drugs to progress to clinical trials. Atropine and oral 7-methylxanthine are shown to reduce myopia progression in human studies. The former has been extensively studied and is arguably the most successful medication. However, it has side effects and trials on low-dose atropine are ongoing. Other pharmaceutical agents being investigated at a clinical trial level include ketorolac tromethamine, oral riboflavin and BHVI2 (an experimental drug). Since the pathophysiology of myopia is not fully elucidated, numerous drugs have been tested at the preclinical stage and can be broadly categorised based on the proposed mechanisms of myopisation, namely antimuscarinic, dopaminergic, anti-inflammatory and more. However, several agents were injected intravitreally or subconjunctivally, hindering their progress to human trials. Furthermore, with atropine being the most successful medication available, future preclinical interventions should be studied in combination with atropine to optimise the treatment of myopia. | {
"pile_set_name": "PubMed Abstracts"
} |
Cytokines hold promise for human embryo culture in vitro: results of a randomized clinical trial.
To evaluate the effects of cytokine enrichment of culture medium on embryological and clinical outcomes after intracytoplasmic sperm injection (ICSI). A randomized clinical trial. In vitro fertilization centers. This trial included 443 ICSI cycles randomized into two groups. This study evaluated the influence of integration of granulocyte-macrophage colony-stimulating factor, heparin-binding epidermal growth factor-like growth factor, and leukemia inhibitory factor into culture media on human embryo development after ICSI. Ongoing pregnancy rate per a randomized participant. Cytokine enrichment of culture medium showed improvement in ongoing pregnancy rate compared with no cytokines (106/224 [47%] vs. 78/219 [36%]; absolute rate difference [ARD] = 12; 95% confidence interval [CI], 2.5-21). This integration of cytokines also showed better rates of live birth (101/224 [45%] vs. 71/219 [33%]; ARD = 13; 95% CI, 4-21) and cumulative live birth (132/224 [60%] vs. 97/219 [44%]; ARD = 12; 95% CI, 4-20) and lower rate of pregnancy loss (27/124 [22%] vs. 37/103 [36%]; ARD = -14; 95% CI, -26 to -2) than conventional medium. Embryos developed in the cytokine-supplemented medium showed better blastocyst formation, quality, cryopreservation, and use than control medium. Integration of cytokines into human embryo culture media showed improvement in embryological and clinical outcomes after ICSI. However, the long-term effect of cytokine enrichment of a medium is still unclear and warrants further studies with longitudinal follow-up. NCT02420886 at ClinicalTrials.gov. | {
"pile_set_name": "PubMed Abstracts"
} |
Resistance to acute nephrotoxicity induced by cadmium-metallothionein dependence on pretreatment with cadmium chloride.
Three groups of rats (B-D) were given various daily doses of CdCl2 (0.5-2 mg Cd/kg) continuously or in intervals during time periods of 1-8 weeks. Another group of animals (A) were kept untreated. At the end of the period, selected subgroups of groups A-D were given a single subcutaneous injection of 109Cd-metallothionein (109CdMT) 0.05 or 0.4 mg Cd/kg ("challenge dose"). Subsequently, urinary creatinine, protein, Cd, 109Cd and MT and kidney cortex Cd, 109Cd and MT were determined. In group A (no long term pretreatment), an increased proteinuria was observed after the rats had received the lower of the challenge doses of 109CdMT, and an even greater increase after the higher challenge dose of 109CdMT. No such increase appeared in group B, C and D (repeatedly pretreated with CdCl2) at either of the challenge doses. Higher metallothionein concentrations in kidney cortex observed in the pretreated groups constitute a plausible explanation of the protective effects of pretreatment against the development of increased proteinuria after challenge dosing. It is likely that increasing Cd concentrations, gradually accumulating in the renal cortex (22-226 micrograms/g wet wt.) as a result of the pretreatment, served to induce the synthesis of metallothionein in the renal cortical cells, thus making them resistant to the challenge from 109CdMT. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of PEG-lipids on permeability of phosphatidylcholine/cholesterol liposomes in buffer and in human serum.
The permeability of liposomal membranes was studied as a function of the amount of incorporated PEG-lipid. The fluorescent dyes ethidium, propidium and 5(6)-carboxy fluorescein were used as markers for measurements of spontaneous leakage. The results show that addition of up to 8 mol% of PEG(2000)-DSPE into liposomal membranes of DSPC/Cho and EPC/Cho reduces the permeability of carboxyfluorescein in buffer solution. In contrast, the leakage of the more amphiphilic dye ethidium was not to any measurable extent affected by PEG-lipid inclusion. Another important difference was that ethidum leakage showed a clear dependence on temperature whereas leakage of carboxyfluorescein from pegylated liposomes did not. We conclude that the mechanisms by which the two dyes permeate the liposomal bilayer are qualitatively different. Both ethidium and carboxyfluorescein did interact with human serum components in a way that made measurements in serum unreliable. The more hydrophilic ethidium analogue propidium was shown not to interact with human serum components to any detectable extent. This made propidium suitable for permeability determinations in human serum. It was found that liposomes composed of pure EPC or EPC with 5 mol% DSPE-PEG, displayed a dramatic increase in permeability when subjected to a medium composed of 20% human serum in buffer. Addition of 40 mol% cholesterol to the EPC bilayers reduced the observed release rate in human serum substantially, whereas no stabilizing effect was observed upon PEG-lipid inclusion. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression of cyanobacterial genes involved in heterocyst differentiation and dinitrogen fixation along a plant symbiosis development profile.
Members of the cyanobiont genus Nostoc, forming an endosymbiosis with members of the angiosperm genus Gunnera, undergo a number of characteristic phenotypic changes during the development of the symbiosis, the genetic background of which is largely unknown. Transcription patterns of genes related to heterocyst differentiation and dinitrogen fixation and corresponding protein profiles were examined, using reverse transcription-polymerase chain reaction and Western blots, along a developmental (apex to mature parts) sequence in Gunnera magellanica and G. manicata and under mimicked symbiotic conditions in a free-living Gunnera isolate (Nostoc strain 0102). The hetR gene was highly expressed and correlated positively with an increase in heterocyst frequency and with ntcA expression, whereas nifH expression was already high close to the growing apex and glnB (P(II)) expression decreased along the symbiotic profile. Although gene expression appeared to be regulated to a large extent in the same fashion as in free-living cyanobacteria, significant differences were apparent, such as the overexpression of both hetR and ntcA and the contrasting down-regulation of glnB, features indicating important regulatory differences between symbiotic and free-living cyanobacteria. The significance of these findings is discussed in a symbiotic context. | {
"pile_set_name": "PubMed Abstracts"
} |
Concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: is intergroup study 0099 feasible in Japanese patients?
Since the publication of the significant results of the Intergroup Study 0099 (IGS) in 1998, radical radiation therapy (RT) with concurrent and adjuvant chemotherapy has become the standard care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in the United States. An update in 2001 further strengthened the findings of the interim analysis, however, no prospective randomized trials other than this study have confirmed the feasibility of this strategy. We attempted to adopt the same combined modality treatment for three consecutive Japanese patients with locoregionally advanced NPC to evaluate its toxicity and efficacy. They were planned to receive radical RT concurrently with cisplatin every 3 weeks, and to receive adjuvant chemotherapy thereafter. The hematological toxicities were mild and well tolerated in all three patients; however, they all experienced severe (grade 3 and/or 4) skin reactions, pharyngitis and dysphagia, which led to the discontinuation of the planned chemotherapy. They were able to complete RT without treatment breaks, and all three patients achieved complete response at the end of treatment. However, two experienced recurrences after 8 and 10 months, respectively, and died of their disease. Due to these severe acute adverse events, poor compliance and unsatisfactory outcomes, we have concluded that physicians should be careful in applying the concurrent chemoradiotherapy protocol employed by the IGS for locoregionally advanced Japanese NPC patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Suprapontine control of respiration.
Despite focus on brainstem areas in central respiratory control, regions rostral to the medulla and pons are now recognized as being important in modulating respiratory outflow during various physiological states. The focus of this review is to highlight the role that suprapontine areas of the mammalian brain play in ventilatory control mechanisms. New imaging techniques have become invaluable in confirming and broadening our understanding of the manner in which the cerebral cortex of humans contributes to respiratory control during volitional breathing. In the diencephalon, the integration of respiratory output in relation to changes in homeostasis occurs in the caudal hypothalamic region of mammals. Most importantly, neurons in this region are strongly sensitive to perturbations in oxygen tension which modulates their level of excitation. In addition, the caudal hypothalamus is a major site for 'central command', or the parallel activation of locomotion and respiration. Furthermore, midbrain regions such as the periaqueductal gray and mesencephalic locomotor region function in similar fashion as the caudal hypothalamus with regard to locomotion and more especially the defense reaction. Together these suprapontine regions exert a strong modulation upon the basic respiratory drive generated in the brainstem. | {
"pile_set_name": "PubMed Abstracts"
} |
BMP-2 gene activated muscle tissue fragments for osteochondral defect regeneration in the rabbit knee.
Previously published data indicate that BMP-2 gene activated muscle tissue grafts can repair large bone defects in rats. This innovative abbreviated ex vivo gene therapy is appealing because it does not require elaborative and time-consuming extraction and expansion of cells. Hence, in the present study, we evaluated the potential of this expedited tissue engineering approach for regenerating osteochondral defects in rabbits. Autologous muscle tissue grafts from female White New Zealand rabbits were directly transduced with an adenoviral BMP-2 vector or remained unmodified. Osteochondral defects in the medial condyle of rabbit knees were treated with either BMP-2 activated muscle tissue implants or unmodified muscle tissue or remained empty. After 13 weeks, repair of osteochondral defects was examined by biomechanical indentation testing and by histology/imunohistochemistry applying an extended O'Driscoll scoring system and histomorphometry. Biomechanical investigations revealed a trend towards slightly improved mechanical properties of the group receiving BMP-2 activated muscle tissue compared to unmodified muscle treatment and empty defect controls. However, a statistically significant difference was noted only between BMP-2 muscle and unmodified muscle treatment. Also, histological evaluation resulted in slightly higher histological scores and improved collagen I/II ratio without statistical significance in the BMP-2 treatment group. Histomorphometry indicated enhanced repair of subchondral bone after treatment with BMP-2 muscle, with a significantly larger bone area compared to untreated defects. Gene activated muscle tissue grafts showed potential for osteochondral defect repair. There is room for improvement via the use of appropriate growth factor combinations. | {
"pile_set_name": "PubMed Abstracts"
} |
Theory of mind and prosocial behavior in childhood: A meta-analytic review.
It has been argued that children who possess an advanced theory of mind (ToM) are more likely to act prosocially, yet the empirical findings are mixed. To address this issue definitively, a meta-analytic integration of all prior literature that met appropriate inclusion criteria was conducted. In total, 76 studies including 6,432 children between 2 and 12 years of age contributed to these analyses. Collapsed across all studies, a significant association emerged (r = .19), indicating that children with higher ToM scores also received higher scores on concurrent measures of prosocial behavior. The magnitude of this effect was similar across ToM assessments requiring identification of others' cognitions versus emotions, and it existed irrespective of whether the ToM measure imposed demands on false belief reasoning or not. The association with ToM was also evident for different subtypes of prosocial behavior (helping, cooperating, comforting). ToM had a similar effect for boys and girls, but was slightly stronger in children aged 6 years or older, relative to their younger peers. Taken together, these findings provide the strongest evidence to date that being able to explicitly consider what other people are thinking and feeling is related to children's tendencies to act prosocially, although the magnitude of the association is relatively weak. (PsycINFO Database Record | {
"pile_set_name": "PubMed Abstracts"
} |
Peripheral muscle weakness and exercise capacity in children with cystic fibrosis.
Exercise intolerance in cystic fibrosis (CF) is attributed to diminished nutritional and pulmonary function. We studied the pathophysiology of such intolerance in relation to muscle force and fat-free mass (FFM), in 15 children with moderately severe symptoms of CF (FEV1 < 80% predicted and/or weight for age < -1 SD of reference median), 13 children with mild symptoms of CF (FEV1 and weight above these thresholds), and 13 healthy controls. Cycle maximal workload (Wmax) and V O2max were assessed. Maximal peripheral muscle force was measured, and FFM was calculated from skinfolds. Patients with mild CF, as compared with matched controls, had lower values of Wmax per kilogram of FFM (3.9 +/- 0.5 versus 4.6 +/- 0.3 W/kg [mean +/- SD], respectively; difference = 0.7 [95% CI = 0.4 to 1.1]), and diminished maximal muscle force (2.7 +/- 0.4 kN versus 3.1 +/- 0.7 kN; difference = 0.44 [95% CI = 0.03 to 0.87]), but similar V O2max. Patients with moderate CF had lower FFM, muscle force, and exercise tolerance than did the other groups. Oxygen cost of work was elevated in both groups of CF patients. Muscle force showed a strong positive correlation with Wmax in patients and controls, with disproportionately lower regression slopes in the CF patients. In children with CF, muscle force is decreased and associated with diminished maximal work load, even in the absence of diminished pulmonary or nutritional status. | {
"pile_set_name": "PubMed Abstracts"
} |
Renal siderosis in donor allograft: pathologic and clinical sequelae.
Transplantation of a cadaver kidney with marked siderosis and its outcome has not been reported. Increasing use of marginal kidneys has become common practice to expand the donor pool to meet the growing demand and will lead to increased recognition of kidney disease in cadaver donors with an unknown effect on graft outcome. This is a case report of a recipient of a cadaver kidney with marked siderosis monitored by surveillance biopsies and evaluated by clinico-pathological correlation. The recipient continued to have transplant kidney function, and a surveillance biopsy shows the natural course of the pathologic resolution of renal siderosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Outpatient conversion of treatment to potassium-sparing diuretics.
Thiazide diuretics frequently cause a decrease in serum potassium levels. In this study, 34 percent of patients taking hydrochlorothiazide had serum potassium levels below 3.5 meq/liter. The response of the serum potassium level was studied after treatment in 56 patients was switched from 50 mg of hydrochlorothiazide daily to either two capsules of hydrochlorothiazide/triampterene (Dyazide), or one tablet of hydrochlorothiazide/amiloride (Moduretic) daily, over nine to 15 months. The 24 patients whose treatment was changed to Dyazide had a rise in serum potassium levels from a mean of 3.56 meq/liter to 4.17 meq/liter in two to three weeks. The 32 patients whose treatment was changed to Moduretic had a rise in serum potassium levels from a mean of 3.76 meq/liter to 4.14 meq/liter in two to three weeks. The resultant rise in potassium levels was stable throughout the follow-up period in both groups. Patient acceptance of this change was excellent. | {
"pile_set_name": "PubMed Abstracts"
} |
[Prevalence of hepatitis C virus antibodies in a hemodialysis unit].
The prevalence of hepatitis C antibody was studied using the EIA 2 Abbott assay in patients and staff of the San Juan de Dios Hospital Hemodialysis Unit. The antibody was detected in 29.8% of patients, no member of the staff had positive antibodies. Patients with a positive antibody had been on hemodialysis for a longer time than those with a negative test (53.3 +/- 18.8 vs 37.9 +/- 33.5 months respectively). No differences in the number of transfusions received were observed between patients with positive or negative antibodies. Hepatitis B surface antigen was detected in 2 patients, with negative hepatitis C virus antibody. No clinical evidence of liver disease was found among patients with positive antibodies. | {
"pile_set_name": "PubMed Abstracts"
} |
Phenolic compounds in wheat grain cultivars.
Three hydroxybenzoic acids: p-hydroxybenzoic acid, vanillic acid and syringic acid; six hydroxycinnamic acids: p-coumaric acid, ferulic acid and four ferulic acid derivatives and a flavonoid (apigenin) were identified and quantified in 34 accessions corresponding to 19 cultivars of wheat applying HPLC coupled to diode array detector. Considerable differences between the wheat cultivars were observed in the phenolic contents. Some cultivars (Colorado, Del País, Barbilla, Jallado, Raspinegro Canario and Plaganudo) could be selected according to the high levels of phenolic compounds. Ferulic acid was the major phenolic acid compound followed by syringic and p-hydroxybenzoic acids. The proportion of ferulic acid present as dimeric forms ranged from 4.2 to 8.6% across all of the wheat cultivars analyzed. Apigenin, p-hydroxybenzoic and syringic acids did not show significant correlations. Many correlations between the determined hydroxycinnamic acids were observed. The ferulic acid and all the ferulic acid derivatives showed highly significant correlations, suggesting that the concentrations of diferulic acids depend on the concentration of ferulic acid. | {
"pile_set_name": "PubMed Abstracts"
} |
Distribution of polyamines may be altered in different scalp regions of patients with hair loss.
Hair loss, from the vertex or front of the head, generally occurs due to increased androgenic steroid levels. Androgenic steroids, particularly testosterone and dihydrotestosterone, are distributed differently across the vertex and occipital regions and are involved in inducing ornithine decarboxylase expression. Therefore, we hypothesized that the distribution of polyamines may be altered in different scalp regions. For the overall metabolic profiling of polyamines in patients with hair loss, a liquid chromatography-mass spectrometry was used. We investigated the differential polyamine levels in different regions of the hair of patients with male pattern baldness and those with female pattern hair loss. The levels of most polyamines were higher in the vertex region than in the occipital region, and N-acetyl polyamine levels differed significantly. We proposed to test our hypothesis by profiling polyamines in human hair fibre to evaluate the distribution of metabolites in various regions of the scalp. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of cyclic cisplatin and etoposide therapy with continuous UFT administration on the recurrence of endometrial cancer in nude mice.
Effects of cisplatin and etoposide chemotherapy and/or continuous administration of oral anticancer agent UFT following the initial chemotherapy with cisplatin and etoposide on the tumor recurrence rate were studied in endometrial cancer-bearing mice. Complete response (CR) rate of cyclic administration of cisplatin and etoposide (91%) was significantly higher than that in the control group (60%; p < 0.05). Continuous UFT administration raised a CR rate of 75%, which was not significantly higher than that of the control group. When cyclic administration of cisplatin and etoposide was combined with continuous UFT administration, 100% of CR rate was obtained (p < 0.01). Our results suggest that cisplatin-based cyclic chemotherapy has a therapeutic effect on gynecologic malignancies and is particularly effective in preventing tumor recurrence in mice. Combining this therapy with continuous administration of an oral anticancer agent enhances its therapeutic effect. | {
"pile_set_name": "PubMed Abstracts"
} |
Intention to quit smoking: is the partner's smoking status associated with the smoker's intention to quit?
Smoking behavior among couples is often similar. The aim of the study was to examine the relationship between the partner's smoking status and the intention to stop smoking of the index person. Cross-sectional data of 1,044 patients in a random sample of 34 general medical practices in northeastern Germany were analyzed. Among smokers with a non-smoking partner (SNP), more intended to quit smoking in the next six months (37.0% vs. 31.4%), compared to smokers with a smoking partner (SSP). Also, more SNP intended to quit in the next four weeks (4.7% vs. 2.7%) compared to SSP. SNP were more active in the use of self-change strategies than SSP. The data confirm that the partner's smoking status is related to the intention to quit smoking. Interventions should address the different needs of both smokers with a smoking partner and those with a non-smoking partner. | {
"pile_set_name": "PubMed Abstracts"
} |
Reduced parathyroid hormone response to peroral phosphate in osteoporotic patients.
To determine whether PTH secretion can be stimulated in osteoporosis by peroral phosphate (1.5 g phosphorus), we have compared serum PTH and urinary cyclic AMP responses in 8 osteoporotic patients with vertebral compression fractures to those of 7 age-matched control subjects. While there was no statistically significant difference in the rise of serum phosphate and urinary phosphate excretion and in the fall of serumionized calcium concentrations, serum PTH and urinary cyclic AMP were increased in control subjects, but not in osteoporotic patients (osteoporotics vs. control group: PTH, p less than 0.01; cyclic AMP/glomerular filtrate, p less than 0.05). Moreover, plasma levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were the same in the 2 groups of subjects. Serum levels of the carboxyl-terminal flanking peptide (PDN-21) encoded by the calcitonin gene and cosecreted with calcitonin were similar in normal and osteoporotic subjects before and 3 min after 1-min intravenous calcium infusions (2 mg/kg body weight), and of calcitonin after the calcium infusions. We conclude that calcitonin and PDN-21 responses to intravenous calcium are the same in normal and osteoporotic subjects, whereas stimulation of PTH secretion by peroral phosphate is impaired in some osteoporotic patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Ki-67 and the Chromosome Periphery Compartment in Mitosis.
The chromosome periphery is a complex network of proteins and RNA molecules (many derived from nucleoli) that covers the outer surface of chromosomes and whose function remains mysterious. Although it was first described over 130 years ago, technological advances and the recent discovery that Ki-67 acts as an organiser of this region have allowed the chromosome periphery to be dissected in previously unattainable detail, leading to a revival of interest in this obscure chromosomal compartment. Here, we review the most recent advances into the composition, structure and function of the chromosome periphery, discuss possible roles of Ki-67 during mitosis and consider why this structure is likely to remain the focus of ongoing attention in the future. | {
"pile_set_name": "PubMed Abstracts"
} |
[Analysis of the reasons for the late detection of malignant tumors (based on data from the Voroshilovgrad Province Oncological Dispensary)].
The share of advanced malignant tumors is approximately 22.9%, the highest incidence rate (57.1%) being among patients aged 51--70 years. They show the following distribution for different sites: gastrointestinal tract--53.12; respiratory system--23.78; female genital organs--8.12; urinary system--6.13 and other sites--8.76%. Among the main causes of the detection of malignant tumors at advanced states are superficial, irregular check-ups, errors in clinical and roentgenologic diagnosis, latent course of the disease late application for medical aid and inadequate knowledge of oncology by general practitioners. With a view to improving the doctors' qualifications and raising the standards of mass screenings, Weeks of Oncologists are being conducted, short-term courses for advanced medical training and specialized oncological mass screenings for occupational tumors are organized; and Evening University of Oncology was established. | {
"pile_set_name": "PubMed Abstracts"
} |
Accuracy of Four Imaging Techniques for Diagnosis of Posterior Pelvic Floor Disorders.
To establish the diagnostic test accuracy of evacuation proctography, magnetic resonance imaging (MRI), transperineal ultrasonography, and endovaginal ultrasonography for detecting posterior pelvic floor disorders (rectocele, enterocele, intussusception, and anismus) in women with obstructed defecation syndrome and secondarily to identify the most patient-friendly imaging technique. In this prospective cohort study, 131 women with symptoms of obstructed defecation syndrome underwent evacuation proctogram, MRI, and transperineal and endovaginal ultrasonography. Images were analyzed by two blinded observers. In the absence of a reference standard, latent class analysis was used to assess diagnostic test accuracy of multiple tests with area under the curve (AUC) as the primary outcome measure. Secondary outcome measures were interobserver agreement calculated as Cohen's κ and patient acceptability using a visual analog scale. No significant differences in diagnostic accuracy were found among the imaging techniques for all the target conditions. Estimates of diagnostic test accuracy were highest for rectocele using MRI (AUC 0.79) or transperineal ultrasonography (AUC 0.85), for enterocele using transperineal (AUC 0.73) or endovaginal ultrasonography (AUC 0.87), for intussusception using evacuation proctography (AUC 0.76) or endovaginal ultrasonography (AUC 0.77), and for anismus using endovaginal (AUC 0.95) or transperineal ultrasonography (AUC 0.78). Interobserver agreement for the diagnosis of rectocele (κ 0.53-0.72), enterocele (κ 0.54-0.94) and anismus (κ 0.43-0.81) was moderate to excellent, but poor to fair for intussusception (κ -0.03 to 0.37) with all techniques. Patient acceptability was better for transperineal and endovaginal ultrasonography as compared with MRI and evacuation proctography (P<.001). Evacuation proctography, MRI, and transperineal and endovaginal ultrasonography were shown to have similar diagnostic test accuracy. Evacuation proctography is not the best available imaging technique. There is no one optimal test for the diagnosis of all posterior pelvic floor disorders. Because transperineal and endovaginal ultrasonography have good test accuracy and patient acceptability, we suggest these could be used for initial assessment of obstructed defecation syndrome. ClinicalTrials.gov, NCT02239302. | {
"pile_set_name": "PubMed Abstracts"
} |
[Clinical variants of neuropsychological disorders during remission in chronic alcoholism].
To study the psychopathological characteristics of remissions in alcoholism, 142 patients aged 32 to 45 years were examined. The anxious hypochondriac, neurasthenia-like, asthenic-depressive, anxious suspicious, anxious depressive, excitable, euphoric, apathetic, dysphoric syndromal variants are described. Correlation of the indicated syndromal variants with the other clinical characteristics of alcoholism made it possible to distinguish a favourable and relatively unfavourable type of remission, providing a possibility of differentiating between the treatment and rehabilitation measures in patients suffering from alcoholism. | {
"pile_set_name": "PubMed Abstracts"
} |
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