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pubmed_288_18923 | The powerful antitumor agents ottelione A and B were synthesized in racemic form by a method that relies on selective ring closing metathesis. Optically pure natural (+)-ottelione A was then made from d-ribose, via an alpha-keto cyclopropane. A key feature of the route is that the cyclopropyl group controls the stereochemistry in the attachment of the ArCH2 unit and is then converted by the action of SmI2 into a vinyl group, so that the substituents on the resulting five-membered ring have the required trans relationship. Epimerization of an intermediate gave access by the same method to the trans ring fused isomer (-)-ottelione B. | 10.1021/jo702635t |
pubmed_989_6790 | Daphnezomines A and B are structurally unusual Daphniphyllum alkaloids that contain a unique aza-adamantane core skeleton. Herein, a modular approach to these alkaloids is presented that exploits a diverse array of reaction strategies. Commencing from a chiral pool terpene-(S)-carvone, the azabicyclo[3.3.1]nonane backbone, which occurs widely in Daphniphyllum alkaloids, was easily accessed through a Sharpless allylic amination and a palladium-catalyzed oxidative cyclization. A protecting group enabled a stereoselective B-alkyl Suzuki-Miyaura coupling sequence and an Fe-mediated hydrogen atom transfer (HAT)-based radical cyclization were then applied to construct C6 and C8 stereocenters. A final epimer locking strategy enabled the assembly of the highly congested aza-adamantane core, thereby achieving the first total synthesis of (-)-daphnezomines A and B in 14 steps. | 10.1021/jacs.0c06717 |
pubmed_1122_1470 | Neurotransmitter release from synaptic vesicles is triggered by voltage-gated calcium influx through P/Q-type or N-type calcium channels. Purification of N-type channels from rat brain synaptosomes initially suggested molecular interactions between calcium channels and two key proteins implicated in exocytosis: synaptotagmin I and syntaxin 1. Co-immunoprecipitation experiments were consistent with the hypothesis that both N- and P/Q-type calcium channels, but not L-type channels, are associated with the 7S complex containing syntaxin 1, SNAP-25, VAMP and synaptotagmin I or II. Immunofluorescence confocal microscopy at the frog neuromuscular junction confirmed that calcium channels, syntaxin 1 and SNAP-25 are co-localized at active zones of the presynaptic plasma membrane where transmitter release occurs. Experiments with recombinant proteins were performed to map synaptic protein interaction sites on the alpha 1A subunit, which forms the pore of the P/Q-type calcium channel. In vitro-translated 35S-synaptotagmin I bound to a site located on the cytoplasmic loop linking homologous domains II and III of the alpha 1A subunit. This direct link would target synaptotagmin, a putative calcium sensor for exocytosis, to a microdomain of calcium influx close to the channel mouth. Cysteine string proteins (CSPs) contain a J-domain characteristic of molecular chaperones that cooperate with Hsp70. They are located on synaptic vesicles and thought to be involved in modulating the activity of presynaptic calcium channels. CSPs were found to bind to the same domain of the calcium channel as synaptotagmin, and also to associate with VAMP. CSPs may act as molecular chaperones in association with Hsp70 to direct assembly or dissociation of multiprotein complexes at the calcium channel. | 10.1098/rstb.1999.0380 |
pubmed_730_9619 | Stress disturbs homeostasis by altering the equilibrium of various hormones which have a significant impact on immune responses. Few studies have examined the influence of stressors on autoimmune disease in animal models. In our work, we studied the effects of long-term exposure (14 days) to chronic varied stress (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar rats. We studied whether the exposure to CVS before or after the immune challenge would correlate with differences in the clinical course of the disease. We also examined whether the CVS would modulate the magnitude of the cellular or the humoral immune response. We observed opposite effects on the clinical signs in animals stressed before or after the immune challenge. The clinical signs of the disease were attenuated in animals stressed before but not after the immune challenge. Relationships were found in the modulation of the clinical severity related to the time of exposure to the CVS, the histological alterations and the proliferative results. Stressed animals with milder clinical signs presented an exacerbated humoral response against myelin antigens while stressed animals with more severe clinical symptoms exhibited a significantly diminished one. Besides, we detected the presence of specific IgG1 associated with the exposure to CVS before the induction of EAE. Our results show that, depending on the timing of the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a more pronounced humoral or cellular profile of the response. | 10.1006/brbi.1998.0519 |
pubmed_615_23402 | The plant-pathogenic fungus Verticillium longisporum is a causal agent of early senescence and ripening in cruciferous crops like Brassica napus. Verticillium wilts have become serious agricultural threats in recent decades. Verticillium species infect host plants through the roots and colonize xylem vessels of the host plant. The xylem fluid provides an environment with limited carbon sources and unbalanced amino acid supply, which requires V. longisporum to induce the cross-pathway control of amino acid biosynthesis. RNA-mediated gene silencing reduced the expression of the two CPC1 isogenes (VlCPC1-1 and VlCPC1-2) of the allodiploid V. longisporum up to 85%. VlCPC1 encodes the conserved transcription factor of the cross-pathway control. The silenced mutants were highly sensitive to amino-acid starvation, and the infected plants showed significantly fewer symptoms such as stunting or early senescence in oilseed rape plant infection assays. Consistently, deletion of single CPC1 of the haploid V. dahliae resulted in strains that are sensitive to amino-acid starvation and cause strongly reduced symptoms in the plant-host tomato (Solanum lycopersicum). The allodiploid V. longisporum and the haploid V. dahliae are the first phytopathogenic fungi that were shown to require CPC1 for infection and colonization of their respective host plants, oilseed rape and tomato. | 10.1094/MPMI-06-13-0181-R |
pubmed_307_20091 | BACKGROUND
A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT).
METHODS
A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23).
RESULTS
All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22% in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0%) compared with the CYA-ME group (17%, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35%) compared with the 4-hr CYA-IV group (7%, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose.
CONCLUSIONS
In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance. | 10.1097/TP.0b013e31821dcae3 |
pubmed_960_11582 | Acute encephalopathic crisis in glutaryl-CoA dehydrogenase deficiency results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and secondary complications, and quite often leading to early death. The prerequisite for the prevention of irreversible brain damage in this disease is the detection of affected patients and initiation of treatment before the manifestation of such crisis. Apart from macrocephaly there are no signs or symptoms characteristic for this disease in presymptomatic children and, thus, they are usually missed. In some countries, implementation of extended neonatal screening programmes using electrospray ionization tandem mass spectrometry (ESI-MS/MS) allows detection of affected newborns and start of therapy before onset of neurological complications. This article summarizes recent strategies, pitfalls and shortcomings of a mass screening for glutaryl-CoA dehydrogenase deficiency using ESI-MS/MS. Furthermore, an alternative strategy, namely DNA-based neonatal screening for the Oji-Cree variant of this disease, is demonstrated. An optimization of diagnostic as well as therapeutic procedures must be achieved before GCDH deficiency unequivocally fulfills the criteria of a reliable and successful newborn screening programme. | 10.1023/B:BOLI.0000045769.96657.af |
pubmed_426_1290 | Genetic and molecular analyses indicate that the Drosophila engrailed gene is required to distinguish posterior from anterior compartments in each segment of the developing animal. Here, the patterns of engrailed expression in the imaginal discs and ventral ganglion of Drosophila larvae are examined, using an antiserum against the engrailed protein and a novel image processing method to reduce non-specific background. As expected, engrailed expression generally is restricted to cells in the posterior compartment of the discs, and the patterns of expression allow refinements in the fate maps of the discs to be made. More significant is the finding that expression of the gene is highly variable in different regions of posterior compartments, suggesting that engrailed may do more than simply specify 'posteriorness'. In the ventral ganglion engrailed appears to be expressed by a subset of cells, primarily in the posterior regions of each segment. In wing discs from animals that are homozygous for the en1 mutation, the pattern of expression of the gene is altered, as opposed to being simply reduced uniformly in the posterior cells. | 10.1002/j.1460-2075.1986.tb04547.x |
pubmed_810_13851 | We created nanometer-scale transmembrane channels in lipid bilayers by means of self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to create a stem that penetrated and spanned a lipid membrane, as well as a barrel-shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In single-channel electrophysiological measurements, we found similarities to the response of natural ion channels, such as conductances on the order of 1 nanosiemens and channel gating. More pronounced gating was seen for mutations in which a single DNA strand of the stem protruded into the channel. Single-molecule translocation experiments show that the synthetic channels can be used to discriminate single DNA molecules. | 10.1126/science.1225624 |
pubmed_74_5076 | Catheter-related bloodstream infections (CRBSIs) commonly arise from a parenteral nutrition catheter hub. A target for a Nutrition Support Team is to have a CRBSI rate of less than 1 per 1000. The diagnosis of CRBSI is suspected clinically by a temperature shortly after setting up a feed, general malaise or raised blood inflammatory markers. It is confirmed by qualitative and quantitative blood cultures from the catheter and peripherally. Treatment of inpatients may involve central venous catheter removal and antibiotics for patients needing short-term parenteral nutrition, but catheter salvage is generally recommended for patients needing long-term parenteral nutrition, where appropriate. | 10.1136/flgastro-2018-101094 |
pubmed_289_3581 | Miniaturized pressurized solvent extraction vessels were used to examine polychlorinated biphenyl congener (PCB) concentrations in 0.2 g sample sizes of whole blood, liver, heart and breast tissue sampled from twelve Great Lakes Mallard ducks (Anas platyrhynchos). This study successfully supported the blood extraction method, previously validated only using laboratory prepared blood samples, using field samples. In situ clean-up offered excellent sample throughput without degradation of GC-MS performance; using this method, extraction, instrument analysis and data interpretation for 100 samples could be accomplished within a one to two week time period. Results indicated contamination in the blood (∑PCB = 1.9-13 ng g(-1) ww), liver (∑PCB = 0.8-11 ng g(-1) ww), breast (∑PCB = <0.1-9 ng g(-1) ww) and heart tissue (∑PCB = <0.1-6 ng g(-1) ww). Quality control included the analysis of blank samples, NIST SRM 1589a and a duplicate of each sample type (blood or tissue). All blank samples were below the method detection limit, SRM values were within 70% of their certified values and duplicates were within 70% of each other. Correlations were examined for the suite of analysed congeners between blood and various tissues; within select individuals a strong and significant correlation was observed. TEQs were calculated and compared against known toxicity data for bird species. Based on the PCB levels found in this study, no adverse health effects are expected in the birds themselves. ∑PCB concentrations in the breast tissue were also compared against both the Canadian and American guidelines for the consumption of edible poultry and based on these values, the Mallards used in this research would be safe for human consumption. | 10.1039/c3em00104k |
pubmed_1064_3379 | Inducible nitric oxide synthase (iNOS) functions as a homodimer. In cell extracts, iNOS molecules partition both in cytosolic and particulate fractions, indicating that iNOS exists as soluble and membrane associated forms. In this study, iNOS features were investigated in human intestinal epithelial cells stimulated with cytokines and in duodenum from mice exposed to flagellin. Our experiments indicate that iNOS is mainly associated with the particulate fraction of cell extracts. Confocal microscopy showed a preferential localization of iNOS at the apical pole of intestinal epithelial cells. In particulate fractions, iNOS dimers were more abundant than in the cytosolic fraction. Similar observations were seen in mouse duodenum samples. These results suggest that, in epithelial cells, iNOS activity is regulated by localization-dependent processes. | 10.1111/j.1742-4658.2004.04484.x |
pubmed_1115_19420 | The human ink4a/arf locus encodes two cell cycle regulatory proteins - the cyclin-dependent kinase inhibitor (p16(ink4a)), and the p53 activator (ARF) - through the use of alternative first exons. This genomic organization is unique in eukaryotes, with two different proteins obtained using different reading frames. The divergence between mouse or opossum and human ARF is very high, whereas proteins have the same nucleolar localization and function. To gain further insights into the relative importance of ARF in different settings, we characterized here the exon 1beta of ARF in 12 different species of primates. We did not find any polymorphism in studied species (monkeys, apes, and humans). These sequences are very similar, with few amino acids substitutions compared to the human sequence. It is strange to find such a high degree of conservation among primates when there is such a low degree of conservation between the human pig, rat, or mouse, chicken exon 1beta sequences. More surprisingly, we observe a threonine at position 31 in all human sequences, whereas an alanine is always present in other sequences. We suggest that when the radiation human/simian appeared or after, a selection of threonine occurred. Moreover, the modifications detected could play a role in different interactions between ARF and other proteins to stabilize or not these complexes. | 10.1089/104454904322964760 |
pubmed_371_21494 | The results of surgical treatment of II-III degree incontinence of feces in 6 patients previously operated on for anorectal anomaly are presented. Clinico-functional examination permitted topical verification of damage to rectal sphincter apparatus. Sphincterolevatoroplasty with the use of a posterior sagittal approach was performed. The given approach permitted maximum use of the preserved muscular elements of the obturator apparatus. In a number of cases sphincterolevatoroplasty was combined with smooth muscle plasty of the internal anal sphincter from the distal colon. The functional results followed in 5 patients were considered as good and satisfactory ones. | pubmed_371_21494 |
pubmed_143_20422 | Objective: The aim of the present study was to assess whether the WASPLab automation enables faster detection of vancomycin-resistant Enterococcus (VRE) on chromogenic VRE-specific plates by shortening the incubation time. Methods: Ninety different VRE culture negative rectal ESwab specimens were spiked with various concentrations (ranging from 3 × 102 to 3 × 107 CFU/ml) of 10 Enterococcus faecium strains (vancomycin MICs ranging from 32 to >256 mg/l), 3 E. faecium VanB strains (vancomycin MICs: 4, 8, and 16 mg/l), and 2 E. faecium VanB strains displaying vancomycin heteroresistance (vancomycin MICs: 64 and 96 mg/l). Results: Besides the two strains exhibiting vancomycin heteroresistance, all the other 13 VRE strains included in this study were detected as early as 24 h on the WASPLab even if the inoculum was low (3 × 103 CFU/ml). When the vancomycin MICs were high, all strains were detected as early as at 18 h. However, 30 h was a conservative time point for finalizing the analysis of chromogenic cultures. Conclusion: These results suggested that the WASPLab automated incubation could allow decreasing the initial incubation time to 18 h, followed by an intermediate time at 24 h and a final incubation period of 30 h for VRE culture screening, to deliver rapid results without affecting the analytical sensitivity. | 10.3389/fcimb.2019.00379 |
others_199_2974 | Parasites of the genus Eimeria are involved in the neonatal diarrhea complex of alpaca (Vicugna pacos) crias, and infection by Eimeria is commonly known as coccidiosis. There are limited reports of these protozoa in clinically asymptomatic crias. In this study, fecal samples from 78 clinically asymptomatic alpaca crias were analyzed to evaluate the prevalence, parasitological load, and diversity of Eimeria species. This study was conducted in the Quenamari community located in the Peruvian Andes (Marangani, Cuzco) at 4500 m above sea level. All fecal samples were examined for parasites using the quantitative McMaster and modified Stoll techniques. Microscopic examination showed the presence of Eimeria oocysts in 68 out of the 78 samples (87.18%). Among the 78 samples we found E. lamae in 67 (85.90%), E. punoensis in 49 (62.82%), E. alpacae in 42 (53.85%), E. macusaniensis in 32 (41.03%), and E. ivitaensis in four (5.13%). Regarding parasitized crias, overall there was a mean parasitological load of 43,920 oocysts per gram of feces (OPG). Eimeria lamae had the highest parasitological load (mean 206,600 OPG). These findings could be due to environmental contamination with oocysts of different Eimeria species. Additional research is needed to determine if this burden of coccidiosis could produce subclinical impacts to the health of alpaca crias. © 2021 Elsevier B.V | 10.1016/j.parint.2021.102438 |
pubmed_923_8961 | The major sulfated polysaccharide in the sea cucumber body wall is a fucose-branched chondroitin sulfate. This glycosaminoglycan has side-chain disaccharide units of sulfated fucopyranosyl or sulfate esters linked to the O-3 position of the beta-D-glucuronic acid residues. These unusual fucose branches and sulfate esters block the access of chondroitinases to the chondroitin sulfate core [Vieira & Mourão (1988) J. Biol. Chem. 263, 18176-18183; Vieira et al. (1991) J. Biol. Chem. 266, 13530-13536]. We now report the isolation and preliminary characterization of the proteoglycans bearing this unique fucose-branched chondroitin sulfate. They were extracted using guanidine hydrochloride solutions containing protease inhibitors and were purified by anion-exchange and gel-filtration columns. Interestingly, the sea cucumber proteoglycans were cleaved by chondroitinase AC or ABC, indicating that the beta-D-glucuronic acid residues close to the reducing end of the polysaccharide chain are neither fucosylated nor sulfated. SDS-polyacrylamide gel electrophoresis revealed several fractions of proteoglycans of different molecular sizes but containing a similar hexuronic acid/protein ratio and a similar type of glycan chain. Possibly, the low-molecular-size fractions arise from a protease cleavage of a larger molecule. In contrast with the results observed for most vertebrate proteoglycans, which contain a single core protein for each type of proteoglycan, chondroitinase AC or ABC releases from the sea cucumber proteoglycans a wide variety of core proteins. These observations are the first detailed study of a proteoglycan from invertebrate tissue and reveal extensive heterogeneity when compared with proteoglycans from vertebrate connective tissue. | 10.1021/bi00060a018 |
pubmed_565_21193 | The diffusion-limited kinetics of the growth of a depletion zone around a static point trap in a thin, long channel geometry was studied using a laser photobleaching experiment of fluorescein dye inside a flat rectangular capillary. The dynamics of the depletion zone was monitored by the theta distance, defined as the distance from the trap to the point where the reactant concentration has been locally depleted to the specified survival fraction (theta) of its initial bulk value. A dimensional crossover from two dimensions to one dimension, due to the finite width of the reaction zone, was observed. We define a "parallel" and a "perpendicular" theta distance, along the slab long and short dimensions, respectively, and study their time development as a means to study the asymmetrical nature of the slab geometry. For all theta values, the crossover occurs concurrently for both theta distances when the depletion zone touches the boundary for the first time. We derive theoretical expressions for this geometry and compare them with the experimental data. We also obtain important insight from the ratio of the reactant concentration profiles in the parallel and perpendicular directions. Exact enumeration and Monte Carlo simulations support the anomalous depletion scaling results. Nevertheless, the crossover time (tau(c)) is still found to scale with the width (W) of the rectangular reaction zone as tau(c) approximately W2 , as expected from the basic Einstein diffusion law. | 10.1103/PhysRevE.71.031107 |
pubmed_702_1246 | Trialkyl phosphate esters are a class of anthropogenic organics commonly found in surface waters of Europe and North America, due to their frequent application as flame retardants, plasticizers, and solvents. Four trialkyl phosphate esters were evaluated to determine second-order rates of reaction with ultraviolet- and ozone-generated *OH in water. Tris(2-butoxyethyl) phosphate (TBEP) was fastest to react with *OH (kOH,TBEP = 1.03 x 10(10) M(-1) s(-1)), followed sequentially by tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris(2-chloroisopropyl) phosphate (TCPP) (kOH,TBP = 6.40 x 10(9), kOH,TCEP = 5.60 x 10(8), and kOH,TCPP = 1.98 x 10(8) M(-1) s(-1)). A two-stage process was used to test the validity of the determined kOH for TBEP and the fastest reacting halogenated alkyl phosphate, TCEP. First, *OH oxidation of TCEP and TBEP, in competition with nitrobenzene was measured in ozonated hydrogen peroxide solutions. Applying multiple regression analysis, it was determined that the UV/H2O2 and O3/H2O2 data sets were statistically identical for each compound. The subsequent validated kOH were used to predict TCEP and TBEP photodegradation in neutral pH, model surface water after chemical oxidant addition and UV irradiation (up to 1000 mJ/cm2). The insignificant difference between the predicted TBEP and TCEP photodegradation and a best-fit of the first-order exponential decay function to the observed TBEP and TCEP concentrations with increasing UV fluence was further evidence of the validity of the determined kOH. TBEP oxidation rates were similar in the surface waters tested. Substantial TCEP oxidation in the model surface water required a significant increase in initial H2O2. | 10.1021/es8031659 |
pubmed_916_16137 | The fabrication of block copolymer (BCP) thin films is reported with vertically aligned cylindrical domains using continuous electrospray deposition onto bare wafer surfaces. The out-of-plane orientation of hexagonally packed styrene cylinders is achieved in the "fast-wet" deposition regime in which rapid evaporation of the solvent in deposited droplets of polymer solution drives the vertical alignment of the self-assembled structure. Thermally activated crosslinking of the polybutadiene matrix provides kinetic control of the morphology, freezing the vertical alignment and preventing relaxation of the system to its preferred parallel orientation on the nontreated substrate. Physically continuous vertically oriented domains can be achieved over several micrometers of film thickness. The ability of electrospray deposition to fabricate well-ordered and aligned BCP films on nontreated substrates, the low amount of material used relative to spin-coating, and the continuous nature of the deposition may open up new opportunities for BCP thin films. | 10.1002/marc.201500099 |
pubmed_1072_6097 | To perform a systemic review and meta-analysis of the diagnostic accuracy of PET (CT) and metaiodobenzylguanidine (MIBG) for diagnosing neuroblastoma (NB), electronic databases were searched as well as relevant references and conference proceedings. The diagnostic accuracy of MIBG and PET (CT) was calculated for NB, primary NB, and relapse/metastasis of NB based on their sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUSROC) in terms of per-lesion and per-patient data. A total of 40 eligible studies comprising 1134 patients with 939 NB lesions were considered for the meta-analysis. For the staging of NB, the per-lesion AUSROC value of MIBG was lower than that of PET (CT) [0.8064±0.0414 vs. 0.9366±0.0166 (P<0.05)]. The per-patient AUSROC value of MIBG and PET (CT) for the diagnosis of NB was 0.8771±0.0230 and 0.6851±0.2111, respectively. The summary sensitivity for MIBG and PET (CT) was 0.79 and 0.89, respectively. The summary specificity for MIBG and PET (CT) was 0.84 and 0.71, respectively. PET (CT) showed higher per-lesion accuracy than MIBG and might be the preferred modality for the staging of NB. On the other hand, MIBG has a comparable diagnosing performance with PET (CT) in per-patient analysis but shows a better specificity. | 10.1007/s11596-017-1785-x |
pubmed_238_16980 | The pollution of aquatic ecosystems due to the elevated concentration of a variety of contaminants, such as metal ions, poses a threat to humankind, as these ecosystems are in high relevance with human activities and survivability. The exposure in heavy metal ions is responsible for many severe chronic and pathogenic diseases and some types of cancer as well. Metal ions of the groups 11 (Cu, Ag, Au), 12 (Zn, Cd, Hg), 14 (Sn, Pb) and 15 (Sb, Bi) highly interfere with proteins leading to DNA damage and oxidative stress. While, the detection of these contaminants is mainly based on physicochemical analysis, the chemical determination, however, is deemed ineffective in some cases because of their complex nature. The development of biological models for the evaluation of the presence of metal ions is an attractive solution, which provides more insights regarding their effects. The present work critically reviews the reports published regarding the toxicity assessment of heavy metal ions through Allium cepa and Artemia salina assays. The in vivo toxicity of the agents is not only dose depended, but it is also strongly affected by their ligand type. However, there is no comprehensive study which compares the biological effect of chemical agents against Allium cepa and Artemia salina. Reports that include metal ions and complexes interaction with either Allium cepa or Artemia salina bio-indicators are included in the review. | 10.1007/s00775-022-01963-2 |
pubmed_767_5097 | Objective
To examine individual differences in pediatric cancer survivors' psychosocial adjustment and test the psychosocial predictors, assessed 2-3 years earlier, of those differences.
Method
Pediatric cancer survivors (n = 209, aged 8-17 years at baseline) and their parents were followed for 4 years. They provided reports of survivors' psychosocial adjustment at 3 years post-baseline, and latent profile analysis (LPA) was used to identify subgroups of survivors who differed on those reports. Multinomial logistic regression was used to predict group membership from self- and parent-reported psychosocial factors at baseline (child adjustment, disposition, and parental functioning) and at 1 year post-baseline (child social relations).
Results
The LPA revealed a 3-class model as the best fit: a "Resilient" group (65%), characterized by good psychosocial adjustment; a "Self-Reported At-Risk" group (23%), characterized by subclinical elevations in self-reported internalizing and attention problems; and a "Parent-Reported At-Risk" group (12%), characterized by subclinical elevations in parent-reported internalizing, externalizing, and attention problems and in self-reported attention problems. Several psychosocial predictors, including child posttraumatic stress, affectivity, and connectedness to school, as well as parental distress and overprotection, differentiated the Resilient group from the other groups, in expected directions.
Conclusions
The majority of pediatric cancer survivors exhibit enduring resilience. The protective factors identified for them-including positive affectivity and strong connectedness to school-may inform targeted prevention strategies for the minority of survivors who are at risk for maladjustment. | 10.1093/jpepsy/jsy037 |
pubmed_515_2522 | Asymmetric organometallic and organocatalytic processes in aqueous systems are currently of great interest. A few years ago, only a few practitioners studied the subject; now organic reactions in water have become one of the most exciting research areas. The quest to identify water-compatible catalysts has evoked an intense search for new possibilities. Following nature's lead, the application of amino acids as sources of chiral information seems particularly promising for aqueous systems. Herein we provide an overview of very recent advances in the area of asymmetric catalysis in water with amino acids and their derivatives as effective catalysts or essential components of catalysts. | 10.1002/anie.200802038 |
pubmed_334_10214 | BACKGROUND
There are limited findings about dietary patterns and food preferences among patients suffering from schizophrenia. The main objective of this study was therefore to compare the nutritional pattern of schizophrenia patients with that of matched healthy subjects.
METHODS
The dietary pattern of 30 hospitalized 16-67 years old schizophrenic patients (11 female) was compared with that of 30 healthy age and sex matched individuals as control group. Subjects' anthropometric measurements including weight, height and body mass index (BMI), semi-quantitative food frequency (FFQ), medical and food history questionnaires were also collected and FFQs were then scored using Food Guide Pyramid to obtain the dietary scores. Percent body fat (%BF) was measured using bioelectrical impedance analysis (BIA) method.
RESULTS
Female patients had more %BF and lower dietary pattern scores than that of their controls (32 +/- 3.6 vs 27.7 +/- 4.6 percent and 43.2 +/- 11.9 vs 54.5 +/- 10.7 points; respectively, p < 0.05 for both). They also consumed less milk and dairy products, fresh vegetables, fruits, chicken, and nuts compared with the female controls (p < 0.03). However, these patients used to eat more full-fat cream and carbonated drinks (p < 0.05). Male patients had lower BMI (22 +/- 4.7 vs 25.6 +/- 4.4; p < 0.05) than their counterpart controls but there was no significant difference between their %BFs. Moreover, they used to have more full-fat cream, hydrogenated fats, less red meat and nuts compared with the male controls (p < 0.05).
CONCLUSION
Schizophrenia patients have poor nutritional patterns. In particular, female patients have more percent body fat and lower dietary pattern scores compared with their healthy controls. All patients used to consume more fats and sweet drinks frequently. The findings of this study suggest that schizophrenia patients need specific medical nutrition therapies through limiting dietary fats and sugars intakes and weight control. Whether obesity is the consequence of disease, dietary preference or medications used remains to be cleared. | 10.1186/1471-244X-7-15 |
pubmed_1124_20384 | In spite of many well-documented examples of age-related reductions in neuronal plasticity, the causes of such changes remain largely unknown. One example of age-reduced plasticity involves an aberrant sprouting response of mature rat sympathetic neurons into the CNS (hippocampal formation). This phenomenon has proven to be useful for exploring the relative contribution of target aging (extrinsic influences) versus neuronal aging (intrinsic influences) to reduced sprouting. Aged sympathetic neurons mount a robust growth response when confronted with young target tissue or when exposed to exogenous trophic factor in vivo. In contrast, the aged target tissue (the hippocampal formation in this example) exhibits reduced receptivity for sympathetic sprouting. This change in the target does not appear to be due to alterations in baseline levels of trophic or substrate support for axonal growth. Rather, aging appears to dampen the consequences of target denervation so that the aged target elicits less sprouting. Age-related reductions in neuronal sprouting are speculated to reflect increasing commitment to information storage at the expense of neuronal plasticity. | 10.1016/s1566-0702(01)00373-3 |
pubmed_632_2057 | Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the role of myocyte Ca2+ handling in the remote myocardium 24 h after 60 min LAD occlusion. Cardiomyocytes isolated from the basal noninfarct-related parts of wild type mouse hearts demonstrated depressed beat-to-beat Ca2+ handling. The amplitude of the Ca2+ transients as well as the kinetics of Ca2+ transport were reduced by up to 25%. These changes were associated with impaired sarcomere contraction. While expression levels of Ca2+ regulatory proteins were unchanged in remote myocardium compared to the corresponding regions of sham-operated hearts, mobility shift analyses of phosphorylated protein showed 2.9 ± 0.4-fold more unphosphorylated phospholamban (PLN) monomers, the PLN species that inhibits the Ca2+ ATPase SERCA2a (P ≤ 0.001). Phospho-specific antibodies revealed normal phosphorylation of PLN at T17 in remote myocardium, but markedly reduced phosphorylation at its PKA-dependent phosphorylation site, S16 (P ≤ 0.01). The underlying cause involved enhanced activity of protein phosphatases, particularly PP2A (P ≤ 0.01). In contrast, overall PKA activity was normal. The PLN interactome, as determined by co-immunoprecipitation and mass spectrometry, and the phosphorylation state of PKA targets other than PLN were also unchanged. Isoproterenol enhanced cellular Ca2+ cycling much stronger in remote myocytes than in healthy controls and improved sarcomere function. We conclude that the reduced phosphorylation state of PLN at S16 impairs myocyte Ca2+ cycling in the remote myocardium 24 h after I/R and contributes to contractile dysfunction. | 10.1016/j.yjmcc.2018.04.004 |
pubmed_894_14514 | Two models ('single-pump' and 'two-pump') of transepithelial potassium movement by the marginal cells of the stria vascularis have been proposed in the literature. Their validity was considered by exposing the endolymphatic (luminal) surface to agents (barium, valinomycin and nystatin) which are known to alter specific cellular membrane conductances in other tissues. This was accomplished by the use either of injections or of a relatively satisfactory technique for perfusion of scala media, which is described. Injection of barium caused the endocochlear potential (EP) to increase in normal animals and had no effect on the EP of deaf, Waltzing guinea pigs. Perfusion of the ionophores caused a decline in the EP in both normal and Waltzing guinea pigs. Only the 'two-pump' model (Na/K-ATPase-mediated cation pump on the basolateral membrane and rheogenic K transporter at the luminal membrane) is consistent with the results. The cellular heterogeneity of the cochlear duct, however, introduces a measure of uncertainty into this interpretation. | 10.1016/0378-5955(83)90116-8 |
pubmed_434_20101 | AIM
This study investigated the prevalence and contributing factors of loss of bone mineral density after renal transplantation among Turkish patients.
PATIENTS AND METHODS
The study included 70 subjects, namely 50 males and 20 females of overall mean age of 36.94 ± 10.09 years. We measured femoral neck mineral density by dual-energy X-ray absorptiometry (DEXA). A T score above -1 was defined as a normal bone mineral density compared with T scores of -1.0 to -2.5 or below -2.5 which were defined as either osteopenia or osteoporosis, respectively.
RESULTS
At a median duration of 23 months after renal transplantation, osteopenia or osteoporosis was observed among 30 (42.9%) or 30 (42.9%) of the 70 patients, respectively. The mean body mass index (BMI) value was significantly higher among the normal than the osteoporotic group: 27.59 ± 4.66 kg/m(2) vs 24.18 ± 3.57 kg/m(2), respectively. However, no significant differences occurred in terms of BMI among the other groups. The amount of proteinuria was significantly lower in the normal than the osteopenic or osteoporotic group: (12.5 (range, 10.0-20.0); 105.0 (10.0-2800.0) or 215.5 (10.0-1880.0) mg/d (P = .001 and .004, respectively). In contrast, there was no significant difference between the amounts of proteinuria displayed by the osteopenic group and the osteoporotic group (P < .05)]. These patient groups showed no difference in age, gender, donor source, cause of end-stage renal disease (ESRD), pretransplant dialysis modality, duration of dialysis, use of a vitamin D preparation, immunosuppressive regimen, posttransplantation period, levels of iPTH or 25 hydroxy vitamin D3 (25OH vit D), exposure to tacrolimus or cyclosporine (CyA), calcium × phosphate product, serum albumin and hemoglobin content, creatinine clearance, or serum bicarbonate concentrations (P > .05). The T scores of the femoral neck correlated with BMI (r: 0.415; P = .001), 25OH vit D level (r: 0.268, P = .026), creatinine clearance (r: 0.273, P = .022), and serum glucose level (r: 0.349, P = .003). It inversely correlated with the amount of proteinuria (r: -0.263, P = .028), serum alkaline phosphatase level (r: -0.329, P = .005), and serum magnesium concentration (r: -0.252, P = .035). Upon multivariate analysis, BMI and 25OH vit D level were observed to be independent risk factors for loss of femoral mineral density.
CONCLUSION
Loss of bone mineral density is a common complication that correlates with low BMI values and decreased 25OH vit D levels as major risk factors for this problem. | 10.1016/j.transproceed.2010.07.106 |
pubmed_1096_7793 | PURPOSE
Synchronised intermittent mandatory ventilation (SIMV) and high-frequency jet ventilation (HFJV) are accepted ventilatory strategies for treatment of respiratory distress syndrome (RDS) in preterm babies. We hypothesised that SIMV and HFJV both facilitate adequate oxygenation and ventilation but that HFJV is associated with less lung injury.
RESULTS
There were no differences in arterial oxygenation or partial pressure of carbon dioxide despite lower mean airway pressure during SIMV for most of the study. There were no consistent significant differences in end systolic and end diastolic PBF, lung injury data and static lung compliance.
METHODS
Preterm lambs of anaesthetised ewes were instrumented, intubated and delivered by caesarean section after intratracheal suction and instillation of surfactant. Each lamb was managed for 3 hr according to a predetermined algorithm for ventilatory support consistent with open lung ventilation. Pulmonary blood flow (PBF) was measured continuously and pulsatility index was calculated. Ventilatory parameters were recorded and arterial blood gases were measured at intervals. At postmortem, in situ pressure-volume deflation curves were recorded, and bronchoalveolar lavage fluid and lung tissue were obtained to assess inflammation.
CONCLUSIONS
SIMV and HFJV have comparable clinical efficacy and ventilator pressure requirements when applied with a targeted lung volume recruitment strategy. | 10.1002/ppul.23187 |
pubmed_95_10033 | HIV infection is characterized by the loss of CD4+ T cell numbers as well as loss of T cell function leading to severe immunodeficiency. The proliferative capacity of T cells, measured in vitro as response to antigens and mitogens, is severely reduced during HIV infection. An increased level of the intracellular second messenger cAMP has been demonstrated to cause impaired proliferative capacity of PBMC from HIV-infected individuals in vitro. We have identified a serotonin analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme responsible for regulation of intracellular levels of cAMP. Using this inhibitor the proliferative responses of PBMC to a polyclone activator in vitro were increased in 28/30 HIV-seropositive individuals (p < 0.00001). Further, we demonstrated that this was due to proliferation of CD4+ T cells and that buspirone induced expression of IL-2 mRNA. | 10.3109/00365549709035870 |
pubmed_133_19212 | Twelve 18-mo-old Debouillet ewes were used to determine the effect of ruminal glucose infusion on DMI, on urinary ammonium (NH4+) and urea N (UUN) concentrations, and on serum metabolite and hormone profiles. Ewes were limit-fed a 90% concentrate diet for 30 d, stratified by BW into three groups (average BW = 82.6+/-1.1 kg), and assigned randomly to receive 0, 5, or 10 g of glucose/kg of BW via esophageal intubation. Urine was collected hourly for 12 h and blood (jugular venipuncture) at 30-min intervals for 12 h. After 12 h, ewes were housed individually, allowed free access to the diet, and DMI was recorded for 5 d. Venous blood pH averaged 7.49, 7.48, and 7.48 at 0 h and decreased (linear [L], P < .01) at 12 h (7.41, 7.36, and 7.26) with increasing glucose. Serum glucose increased (L, P = .06) at 3 and 6 h. Serum L(+)-lactate increased (L, P = .08) at 3, 6, and 9 h, whereas serum D(-)-lactate increased linearly (P = .09) at 6 and 9 h and quadratically (P < .10) at 12 h. After the glucose challenge, DMI decreased (L, P < .05). Urinary pH and NH4+ were not influenced by glucose infusion; however, UUN increased at 3 (quadratic [Q], P < .05), 4, 5, 6 (L, P = .03), and 7 h (Q, P < .05) and decreased at 11 and 12 h (L, P = .09). As glucose infusion increased, serum creatinine increased at 9 (L, P < .01) and 12 h (Q, P = .02). Generally, serum Na and P increased (P = .09), whereas K decreased (P < .05), with glucose infusion. Lactate dehydrogenase activity increased with glucose infusion (Q, P < .10) at 3, 6, 9, and 12 h. Increasing glucose infusion increased serum globulin (Q, P = .06), albumin, and total protein (L, P = .08). Serum prolactin and vasopressin were not influenced (P = .22) by glucose infusion. Serum insulin and aldosterone increased quadratically (P = .08), whereas serum growth hormone decreased linearly (P = .08) as a result of increasing glucose infusion. Results suggest that UUN, serum insulin, aldosterone, and several serum constituents may serve as markers of organic acid load in ruminants fed high-concentrate diets. | 10.2527/1999.77113068x |
pubmed_938_4988 | We report 15 cases of a distinctive variant of thyroid papillary carcinoma designated as "diffuse sclerosing papillary carcinoma" (DSPC). This lesion is characterized by the following morphologic findings: (a) diffuse involvement of one or both lobes, (b) numerous micropapillary formations located within cleftlike spaces consistent with lymph vessels, (c) extensive squamous metaplasia, (d) large number of psammoma bodies, (e) marked lymphocytic infiltration, (f) prominent fibrosis. Of all these features, we believe the widespread intrathyroid lymphatic permeation to be the most important, in the sense of conditioning the other morphologic findings and the behavior of the tumor. When compared with conventional papillary carcinoma, the DSPC variant exhibits the following characteristics: (a) similar predilection for women, (b) younger age at the time of presentation, (c) greater incidence of cervical lymph node involvement, (d) greater incidence of lung metastases, (e) smaller probability of disease-free survival on follow-up. The practical importance of the recognition of this variant of papillary carcinoma lies in its ability to clinically simulate thyroiditis and the more aggressive therapeutic approach that might be needed to eradicate it. | 10.1097/00000478-198912000-00006 |
pubmed_1076_20055 | OBJECTIVES
To compare haloperidol to droperidol, both with dexamethasone, for antiemetic prophylaxis in elective laparoscopic cholecystectomy.
MATERIAL AND METHODS
Prospective, randomized double-blind trial enrolling 75 ASA 1-2 patients who received anesthesia with propofol and remifentanil. After induction, 8 mg of intravenous dexamethasone was administered. After surgery, depending on group assignment, patients received 10 microg x kg(-1) of intravenous haloperidol (n = 25), 10 microg x kg(-1) of droperidol (n = 25), or physiologic saline solution (n = 25). Outcomes recorded were episodes of nausea or vomiting in the postoperative period (first 6 hours and/or 6-24 hours), requirement for antiemetic agents, morphine consumption, pain assessed on a visual analog scale, level of sedation, and adverse effects.
RESULTS
Five patients in the haloperidol group, 6 in the droperidol group, and 13 in the control group experienced an episode of nausea or vomiting in the 24-hour postoperative period (P < .05 between the active treatment groups and the control group). One patient in the haloperidol group, 6 in the droperidol group, and 8 in the control group reported nausea in the first 6 hours (P < .05). Three patients in the haloperidol group, 1 in the droperidol group, and 8 in the control group reported nausea in the later postoperative period (6-24 hours) (P < .05, droperidol vs control). Three patients in the haloperidol group, 1 in the droperidol group, and 7 in the control group experienced late vomiting (P < .05, droperidol vs control).
CONCLUSIONS
Either haloperidol or droperidol in combination with dexamethasone is more effective than dexamethasone alone for antiemetic prophylaxis after laparoscopic cholecystectomy. | pubmed_1076_20055 |
pubmed_995_15440 | The sizes and locations of pulmonary and pleural metastases in chest X-rays of 50 symptomatic and 65 asymptomatic breast cancer patients were compared and correlated to survival. The diameters of the metastases were about the same in both groups as also their distribution. The incidence of pleural fluid was higher in symptomatic patients. The survival curve of symptomatic patients did not deviate from that of the asymptomatic ones. Symptoms in pulmonary metastatic disease do not mean rapid progress of the disease but may be beneficial in that they cause the patient to visit the oncologist early. The cost-effectiveness of chest X-rays in the follow-up is questionable. | pubmed_995_15440 |
pubmed_369_10194 | BACKGROUND
Subacute superior mesenteric vein thrombosis is a rare ischemic intestinal disease which is often characterized by delayed diagnosis due to obscure clinical picture.
CASE REPORT
A 67-year-old woman who presented chronic abdominal pain with mild nausea due to superior mesenteric vein thrombosis was submitted to video capsule endoscopy. We describe, for the first time, the video capsule endoscopy findings in this patient.
CONCLUSION
We emphasize the role of this new technology in the diagnosis of suspected ischemic intestinal diseases. | pubmed_369_10194 |
pubmed_396_16572 | The aim of this study was to generate and identify a novel benzo[a]pyrene (BP)-derived DNA adduct found both in vitro and in vivo. To date, the majority of studies have focused on N(2)-[10 beta(7 beta,8a,9a-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxyguanosine (anti-BPDE-dG), the major adduct generated following bioactivation of BP. However, a second adduct is also formed following bioactivation of BP which has been speculated to result from further metabolism of 9-OH-BP. In order to identify this second reaction pathway, the ultimate DNA binding species, and the DNA base involved, we have synthesized and characterized a dG-derived DNA adduct arising from further bioactivation of 9-OH-BP in the presence of rat liver microsomes. Analysis of the adducted nucleotides was conducted using both the (32)P-postlabeling assay and capillary electrophoresis-mass spectrometry (CE-MS). | 10.1006/bbrc.2000.4161 |
pubmed_286_13384 | Factors predicting prescriptions of triple therapy were investigated in a large group of general practitioners in Italy. In the population treated by identified general practitioners, a cohort of newly diagnosed chronic obstructive pulmonary disease patients was extracted from IMS Health Longitudinal Database during the period 2010-2013. From the diagnosis, 1-year follow-up was evaluated. Thirty-two thousand forty-six newly diagnosed chronic obstructive pulmonary disease patients were evaluated (57.7% male, mean age 67 years). During 2 years prior to diagnosis less than 13% of patients were requested with a pulmonology evaluation and less than 5% with a spirometry; 65.1% cases were prescribed with a respiratory drug, which in 9.6% of cases was inhaled corticosteroid/long-acting β2-agonist fixed-dose combination. Two thousand and twenty eight patients (6.3% of the newly diagnosed chronic obstructive pulmonary disease patients) were treated with triple therapy during the first year of follow-up, whose 858 (42.3%) starting immediately, and 762 (37.6%) following an initial treatment with inhaled corticosteroid/long-acting β2-agonist fixed-dose combination. Being older, being requested with pulmonologist evaluation or spirometry, being prescribed with a inhaled corticosteroid/long-acting β2-agonist fixed-dose combination at diagnosis resulted independent predictors of triple therapy use.
CHRONIC LUNG DISEASE
ENSURING CORRECT PRESCRIPTIONS FOR EARLY-STAGE DISEASE: An improved education program for doctors promoting correct use of medication for chronic lung disease is needed in Italy. Current guidelines state that inhaled corticosteroids (ICSs) should be reserved for patients with severe chronic obstructive pulmonary disease (COPD), but it appears that doctors do not always follow this advice. Fabiano Di Marco, at San Paolo Hospital-Università degli Studi di Milano, and co-workers analyzed data from 32,046 COPD patients newly-diagnosed by family doctors in Italy between 2010 and 2013. When the researchers followed up on patients after 1 year, 2028 (6.3%) of newly-diagnosed patients were being treated with triple inhaled therapy incorporating ICSs-42% of these patients had started triple therapy immediately upon diagnosis. Being an older male and having been prescribed with a ICS/LABA FDC at diagnosis were strong predictors of triple therapy use within 1 year from the diagnosis. | 10.1038/s41533-017-0051-9 |
pubmed_145_897 | The microheterogeneity forms of human alpha-fetoprotein present in amniotic fluid were studied in affinity immunoelectrophoresis using two lectins: concanavalin A and Lens culinaris agglutinin. Ninety-seven samples of amniotic fluid collected throughout gestation were obtained from pregnancies in which there was no fetal malformation. Two samples of amniotic fluid from pregnancies complicated by anencephaly and one sample obtained from an empty gestational sac were also studied. The changes in relative concentrations of AFP microheterogeneity forms during gestation are described. It is suggested that concanavalin A is suitable for the demonstration of malformations of the central nervous system in the first and second trimester of pregnancy while in the third trimester it would be of no value. The results of this study suggest that Lens culinaris agglutinin might be suitable for this purpose in the third trimester of gestation, but this needs to be confirmed in a larger study. The optimal concentrations of both lectins were investigated. In addition, a simple method of rocket affinity electrophoresis is also described. The possible mechanisms responsible for the changes in relative concentrations of microheterogeneity forms of alpha-fetoprotein during gestation and in pathological conditions are discussed. | 10.1016/s0143-4004(84)80017-x |
pubmed_561_7265 | Following an accidental electric shock, a boy with no previous symptoms developed hyperglycaemia, rapidly evolving into diabetes. He was aglycosuric for 24 hours after the shock. Islet cell antibodies were shown shortly after the accident. Although destined to develop diabetes, it seems likely that the electric shock unmasked impaired glucose tolerance. Glucose homoeostasis should be monitored in children following significant electric shocks. | 10.1136/adc.86.3.210 |
pubmed_570_8830 | Extracytoplasmic function (ECF) sigma factors are known to play an important role in the bacterial response to various environmental stresses and can significantly modulate their pathogenic potential. In the genome of Porphyromonas gingivalis W83, six putative ECF sigma factors were identified. To further evaluate their role in this organism, a PCR-based linear transformation method was used to inactivate five ECF sigma factor genes (PG0162, PG0214, PG0985, PG1660, and PG1827) by allelic exchange mutagenesis. All five isogenic mutants formed black-pigmented colonies on blood agar. Mutants defective in PG0985, PG1660, and PG1827 genes were more sensitive to 0.25 mM of hydrogen peroxide compared with the wild-type strain. Isogenic mutants of PG0162 and PG1660 showed a 50% decrease in gingipain activity. Reverse transcription-PCR analysis showed that there was no alteration in the expression of rgpA, rgpB, and kgp gingipain genes in these mutants. Hemolytic and hemagglutination activities were decreased by more than 50% in the PG0162 mutant compared with the wild type. Taken together, these findings suggest that ECF sigma factors can modulate important virulence factors in P. gingivalis. ECF sigma factors encoded by the PG0162 and PG1660 genes might also be involved in the post-transcriptional regulation of the gingipains. | 10.1111/j.1574-6968.2010.02093.x |
others_294_6545 | Purpose: Perillyl alcohol (POH) (4-isopropenyl-cyclohexenecarbinol) is a member of the monoterpenes, which are present in various fruits and vegetables. POH has been demonstrated to be cytotoxic against a variety of experimental cancer cells in vitro and in vivo. Phase I clinical trials have indicated that POH may be useful for human tumor treatment. The purpose of our study was to reveal whether the anticancer effect of POH could be enhanced by hyperthermia. Methods and Materials: SCK mammary carcinoma cells of A/J mice were used. The effects of POH or hyperthermia alone were studied by incubating the cells during exponential growth phase in culture with 0.25-1.0 mM of POH at 37°C for varying lengths of time or heating cells at 41-43°C for varying lengths of time. The combined effect of POH and hyperthermia was investigated by heating the cells with 1 mM of POH at 41-43°C for varying lengths of time. The effects of the treatments were evaluated using the clonogenic cell survival assay and three types of apoptosis assays. Results: An incubation of SCK cells with 1 mM of POH at 37°C for 60 min or hyperthermia at 43°C for 1 h decreased clonogenic cell survival to 40% and 60%, respectively. When the cells were heated at 43°C for 1 h in the presence of 1 mM of POH, clonogenic cell survival decreased to 0.2%, indicating that hyperthermia potentiated the effect of POH to cause clonogenic cell death. Hyperthermia also markedly increased the degree of POH-induced apoptosis. Conclusion: Hyperthermia synergistically potentiates the cytotoxicity of naturally occurring POH against cancer cells. © 2003 Elsevier I | 10.1016/S0360-3016(03)00737-5 |
pubmed_774_1860 | Hexagonal boron nitride (h-BN) catalyst has recently been reported to be highly selective in oxidative dehydrogenation of propane (ODHP) for olefin production. In addition to propene, ethylene also forms with much higher overall selectivities to C2-products than to C1-products. In this work, we report that the reaction pathways over the h-BN catalyst are different from the V-based catalysts in ODHP. Oxidative coupling reaction of methyl, an intermediate from the cleavage of C─C bond of propane, contributes to the high selectivities to C2-products, leading to more C2-products than C1-products over the h-BN catalyst. This work not only provides insight into the reaction mechanisms involved in ODHP over the boron-based catalysts but also sheds light on the selective oxidation of alkanes such as direct upgrading of methane via oxidative upgrading to ethylene or CH O on boron-based catalysts. | 10.1126/sciadv.aav8063 |
pubmed_1103_20327 | Vascular malformations of the upper limb were once thought to be impossible to properly diagnose and treat. We reviewed our experience with these malformations of the upper limb in 270 patients seen over a 28-year period. These anomalies were slightly more common in females than males (ratio, 1.5:1.0). The malformations were categorized as either slow flow (venous, n = 125; lymphatic, n = 47; capillary, n = 32; combined, n = 33) or fast flow (arterial, n = 33). Three categories of fast-flow malformations were identified and designated as types A, B, and C. Over 90% of these lesions could be properly diagnosed by their appearance and growth pattern within the first 2 years of life. Additional radiographic studies were used to confirm this diagnosis and to define specific characteristics. Magnetic resonance imaging with and without contrast best demonstrated site, size, flow characteristics, and involvement of contiguous structures for all types of malformations. Algorithms for treatment of both slow-flow and fast-flow anomalies are presented. Two hundred sixty surgical resections were performed in 141 patients, including 24 of 33 fast-flow anomalies. Preoperative angiographic assessment, with magnified views, was an important preoperative adjunct before any well-planned resection of fast-flow arteriovenous malformations. The surgical strategy in all groups was to thoroughly extirpate the malformation, with preservation of nerves, tendons, joints, and uninvolved muscle, and microvascular revascularization and skin replacement as required. Resections were always restricted to well-defined regions and often completed in stages. Symptomatic slow-flow malformations and types A and B fast-flow anomalies were resected without major sequelae. Type C arterial anomalies, diffuse, pulsating lesions with distal vascular steal, and involvement of all tissues, including bone, progressed clinically and resulted in amputation in 10 of 14 patients. The complication rate was 22% for slow-flow lesions and 28% for fast-flow lesions. | 10.1053/jhsu.1999.1019 |
pubmed_271_25326 | BACKGROUND
Indolent systemic mastocytosis (ISM) is a rare disease characterized by accumulation of abnormal mast cells in various tissues, including bone marrow. Symptoms are usually related to release of mast cell mediators. The aims are to establish the prevalence of osteoporotic fractures in ISM and to investigate the association with serum tryptase and the urinary histamine metabolites, methylhistamine (MH), and methylimidazole acetic acid.
METHODS
The fracture prevalence in 157 patients (65 men; 92 women), mean age 54 ± 12 years, was assessed by vertebral morphometry and data from patient records, supplemented by a questionnaire. Bone mineral density (BMD) of lumbar spine and femoral neck was measured, and tryptase and histamine metabolites were analysed.
RESULTS
We registered 235 lifetime fractures in 154 patients, including 140 osteoporotic (low-energy trauma) fractures, of which 62% were vertebral, 1% hip and 36% other nonvertebral fractures. Osteoporotic fractures and osteoporosis were found in 37% and 28% of the patients, respectively. In men, the prevalence of these osteoporotic manifestations (46% <50 years; 73% ≥50 years) was much higher compared with women (18% <50 years; 58% ≥50 years). Older age, male gender, and higher urinary MH were independently related to the osteoporotic manifestations.
CONCLUSIONS
This first publication about prevalence of fractures and osteoporosis in patients with ISM shows that the risk of osteoporotic fractures is high, especially in men. Higher urinary MH levels are associated with a higher risk of osteoporotic manifestations. Routine measurements of BMD and vertebral morphometry are warranted in these patients for early detection of osteoporosis. | 10.1111/j.1398-9995.2011.02780.x |
pubmed_625_9894 | Exploiting the ability of proteins to self-assemble into architectural templates may provide novel routes for the positioning of functional molecules in nanotechnology. Here we report the engineering of multicomponent protein templates composed of distinct monomers that assemble in repeating orders into a dynamic functional structure. This was achieved by redesigning the protein-protein interfaces of a molecular chaperone with helical sequences to create unique subunits that assemble through orthogonal coiled-coils into filaments up to several hundred nanometers in length. Subsequently, it was demonstrated that functional proteins could be fused to the subunits to achieve ordered alignment along filaments. Importantly, the multicomponent filaments had molecular chaperone activity and could prevent other proteins from thermal-induced aggregation, a potentially useful property for the scaffolding of enzymes. The design in this work is presented as proof-of-concept for the creation of modular templates that could potentially be used to position functional molecules, stabilize other proteins such as enzymes, and enable controlled assembly of nanostructures with unique topologies. | 10.1021/acssynbio.8b00241 |
pubmed_239_24674 | Divergent differentiation or metaplastic change is a rare feature exhibited occasionally in malignant melanoma (MM), which is characterized by the development of morphologically, immunochemically, and/or ultrastructurally nonmelanocytic cells within the tumor. Smooth muscle differentiation in MM is an exceedingly rare phenomenon reported only in a few cases in the literature. We report the case of a 69-year-old woman who presented with a pure dermal amelanotic MM with smooth muscle cell differentiation and an area of rhabdoid morphology, which made the accurate histopathologic diagnostic of MM challenging. | 10.1097/DAD.0000000000000792 |
others_289_12127 | With more than 135 million people in need of humanitarian assistance, with an unprecedented 68.5 million people around the world forced from home, half under the age of 18, nearly 25.4 million refugees, average displacement soaring to 17-25 years, crises have become the ‘new standard’. Crises affect women and men differently. Women and girls are indeed the most impacted, first of all in terms of reduced access to basic services, specifically to health services (preg-nancy, childbirth). On top of that, women and girls are the most vulnerable to the threat of sexual and gender-based violence. As a matter of fact, when crises hit, the humanitarian response very often does not take the gender-specific medicine perspective into due account. Improving the overall framework of gender-specific medicine in humanitarian responses is crucial. Meanwhile some smaller pilot projects, as in South Sudan the project to address the psychosocial needs of internally displaced persons (mainly women and children) and another one targeted at increasing the avail-ability of basic and emergency healthcare services in the maternal and child environment, have helped probe the way forward and find a new pattern for responding. © 2019, Il Pensiero Scientifico Editore s.r.l.. All rights reser | others_289_12127 |
pubmed_9_87 | During the period between 1976 and 1990, 247 patients with pharmaco-resistant complex partial seizures and a documented unilateral epileptogenic area in the mediobasal temporal lobe underwent a selective amygdalo-hippocampectomy procedure at our institution. Biopsy specimens from 224 patients (91% of the total) were available for a retrospective histopathological and immunohistochemical review. The tissue specimens of 23 patients without evidence for a macroscopic lesion have been used for neurochemical studies and could not be evaluated histopathologically. The most common temporal lobe pathology were neoplasms in 126 patients, i.e. 56%. Tumor entities observed included 23 astrocytomas (18% of all tumors), 17 gangliogliomas (13%), 15 oligodendrogliomas (12%), 15 cases of glioblastoma multiforme (12%), 13 pilocytic astrocytomas (10%), 12 oligo-astrocytomas (10%), 11 anaplastic astrocytomas (9%) and 20 tumors of various other histologies. In 23 specimens (10%), small foci of oligodendroglia-like clear cells were found. The frequent association of these foci with low-grade gliomas or neural hamartomas raises the possibility that these structures may serve as precursor lesion for neuroepithelial tumors of the temporal lobe. In 98 cases, pathological changes of non-neoplastic origin were encountered. The most common diagnoses in this group included hippocampal gliosis/sclerosis (49 cases, 22%) and vascular malformations (20 cases, 9%). Hamartomas, i.e. focal accumulations of dysplastic neuro-glial cells were diagnosed in 14 patients (6%). In only four cases have we not been able to detect any microscopic pathology. These results indicate that a high proportion of pharmaco-therapy-resistant complex-partial seizures are caused by neoplasms of the temporal lobe, some of which appear to be strikingly overrepresented in this group of patients. | 10.1007/BF00228577 |
pubmed_167_19800 | Three new phenylspirodrimanes derivatives named stachybotrysins H and I (1 and 2) and stachybotrin E (3), together with one known compound stachybotrylactam (4), were isolated from Stachybotrys chartarum CGMCC 3.5365. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Compounds 1 and 2 showed inhibitory effect towards potassium channel Kv1.3 with IC50 values of 13.4 and 10.9 μM, respectively. | 10.1080/10286020.2018.1551372 |
pubmed_242_7761 | INTRODUCTION
In the past decades, several authors have investigated the genotoxicity caused by exposure to chemicals, but there are no reports on studies analyzing such effects on children in Argentina. The objective of this study was to establish the micronucleus frequency in exfoliated buccal mucosa cells in children from urban areas with environmental exposure (through inhalation) and to compare it with the micronucleus frequency in children from urban regions far from areas subjected to spraying.
POPULATION AND METHODS
Fifty children living in the town of Marcos Juárez (Córdoba) at different distances from pesticide spraying areas and twenty-five children from the city of Río Cuarto (Córdoba), who are considered not exposed to pesticides, were studied; the micronucleus assay in buccal mucosa cells was used.
RESULTS
A significant difference was observed between exposed children living less than 500 m from areas subjected to spraying and those who were not exposed. Forty percent of exposed children suffer some type of persistent condition, which may be associated with chronic exposure to pesticides.
CONCLUSIONS
Results indicate that genotoxicity is present in a group of children compared to the other one, and highlight the importance of the micronucleus assay in buccal mucosa cells for genetic biomonitoring and public health surveillance. This assay is capable of detecting a level of damage that can be reversible. | 10.5546/aap.2015.eng.126 |
pubmed_808_6508 | The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK. Reverse transcription‑quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl‑2 and caspase‑3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p‑p38 MAPK expression, as well as increased cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. No significant differences were observed in apoptosis and apoptosis‑related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future. | 10.3892/mmr.2017.6469 |
pubmed_957_10993 | AIMS
Low cardiorespiratory fitness (CRF) is associated with greater mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis and heart failure. Gal-3 is also associated with a greater risk for cardiovascular mortality. Whether CRF is related with Gal-3 is unclear. The objective of this study was to assess the sex-specific associations of CRF and Gal-3 levels in the general population.
METHODS
Gal-3 concentrations were determined using a sandwich enzyme immunoassay in the population-based Study of Health in Pomerania (SHIP-TREND-0). Sex-stratified linear regression models adjusted for age, current smoking status, and renal function were used. Individuals with left ventricular ejection fraction (LVEF) <40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (estimated glomerular filtration rate <30 mL/min/mm2 ), a history of cancer, and extreme values for Gal-3 (<1st percentile; >99th percentile) were excluded.
RESULTS
A total of n = 1515 participants with a median age of 49 (IQR: 39-60 years, 48% males) were included. In men, a 1 L/min greater VO2 peak was significantly related to 0.50 ng/mL (95% CI -0.8068 to -0.1938, P < 0.01) less Gal-3. In males, a 1 mL/min/kg higher VO2 peak adjusted for body weight was associated with -0.0286 ng/mL (95% CI -0.0052 to -0.0005, P = 0.02) less Gal-3. When VO2 peak was adjusted for lean mass 1 mL/kg/min more was correlated with a -0.0022 ng/mL (95% CI -0.0043 to -0.0007, P = 0.04) less Gal-3. In women, VO2 peak (β -0.2046 95% CI -0.6541 to 0.2449, P = 0.37) and VO2 peak adjusted for lean mass (β -0.0019 95% CI -0.0421 to -0.0050, P = 0.12) were not related with Gal-3, whereas a 1 mL/min/kg higher VO2 peak adjusted for body weight was significantly associated with a -0.0064 ng/mL lower Gal-3 (95% CI -0.0092 to -0.0035, P < 0.01). There were no differences between pre-menopausal and post-menopausal women.
CONCLUSIONS
VO2 peak was associated with Gal-3 only in men, but VO2 peak adjusted for body weight in women and men. Our results suggest that the adverse consequences of low CRF may be mediated by Gal-3. Further research is needed to understand the sex-specific association between CRF and Gal-3 and whether they are clinically relevant. | 10.1002/ehf2.14151 |
pubmed_735_23349 | Proximal humerus fractures are the third most common fracture in the elderly. Although most fractures can be treated conservatively with acceptable outcomes, certain fracture patterns are at high risk for progression to humeral malunions, nonunions, stiffness, and post-traumatic arthrosis. The goal of antegrade humeral nailing of proximal humerus fractures is to provide stability to a reduced fracture that allows early motion to optimize patient outcomes. Certain technical pearls are pivotal in managing these difficult fractures with nails; these include rotator cuff management, respect of the soft tissues, anatomic tuberosity position, blood supply maintenance, knowledge of the deforming forces on the proximal humerus, fracture reduction, and rehabilitation strategies. Modern proximal humeral nail designs and techniques assist the surgeon in adhering to these principles and have demonstrated promising outcomes. Humeral nail designs have undergone significant innovation during the past 40 years and now can provide stable fixation in the humeral shaft distally as well as improved stability in the head and tuberosity fragments, which were the common site of fixation failure with earlier generation implants. Compared with other fixation strategies, such as locking plate fixation, no compelling evidence exists to suggest one technique over another. The purpose of this review is to describe the history, results, new designs, and techniques that make modern intramedullary nailing of proximal humerus fractures a viable treatment option. | pubmed_735_23349 |
pubmed_214_15440 | PURPOSE
To derive a prescriptive sex-specific fetal growth standard and assess clinical management and outcomes according to sex-specific growth status.
MATERIALS AND METHODS
This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational study of 10,038 nulliparas from eight U.S. centers who underwent ultrasounds at 14-20 and 22-29 weeks with outcomes ascertained after delivery. From these, we selected a nested cohort of lower risk participants (excluded those with chronic hypertension, pre-gestational diabetes, suspected aneuploidy, and preterm delivery) to derive a sex-specific equation for expected fetal growth using fetal weights by ultrasound and at birth. We compared the male-female discrepancy in the rate of weight <10th (small for gestational age [SGA]) and >90th (large for gestational age [LGA]) percentiles between the sex-specific and sex-neutral (Hadlock) standards. Using the full unselected cohort, we then assessed outcomes and clinical management according to sex-specific SGA and LGA status.
RESULTS
Overall, 7280 infants in the lower risk nested cohort were used to derive a sex-specific equation with fetal sex included as an equation intercept. The sex-neutral standard diagnosed SGA more often in female newborns (21% vs. 13%, p < .001) and LGA more often in male newborns (5% vs. 3%, p < .001). The sex-specific standard resolved these disparities (SGA: 9% vs. 10%, p = .23; LGA: 13% vs. 13%, p = .58). To approximate an unselected population, 1059 participants initially excluded for risk factors for abnormal growth were then included for our secondary objective (N = 8339). In this unselected cohort, 39% (95% CI 37.0-42.0%) of the 1498 newborns classified as SGA by the sex-neutral standard were reclassified as appropriate for gestational age (AGA) by the sex-specific standard. These reclassified newborns were more likely to be delivered for growth restriction despite having lower risk of morbidity (females) or comparable risk of morbidity (males) compared to newborns considered AGA by both methods. Of the 6485 newborns considered AGA by the sex-neutral standard, 737 (11.4%, 95% CI 10.6-12.2%) were reclassified as LGA by the sex-specific standard. These reclassified newborns had higher rates of cesarean for arrest of descent, cesarean for arrest of dilation, and shoulder dystocia than newborns considered AGA by both methods. None were reclassified from LGA to AGA by the sex-specific standard.
CONCLUSION
The Hadlock sex-neutral standard generates sex disparities in SGA and LGA at birth. Our sex-specific standard resolves these disparities and has the potential to improve accuracy of growth pathology risk stratification. | 10.1080/14767058.2022.2075696 |
pubmed_886_10223 | PURPOSE
The purpose of this study was to characterize a Krt12-Cre knock-in mouse line for corneal epithelium-specific gene ablation and to analyze the allelic selection of the keratin 12 (Krt12) gene during corneal type-epithelium differentiation.
METHODS
Knock-in mice were generated by gene targeting. The authors examined the expression patterns of several reporter genes in the corneas of bitransgenic Krt12cre/+/ROSA(EGFP), Krt12Cre/+/ZEG, and Krt12Cre/+/ZAP mouse lines. Krt12 and cre recombinase (Cre) immunostaining was performed. Corneal epithelial cells from bitransgenic Krt12Cre/+/ROSA(EGFP) mice were examined by fluorescence-activated cell sorter.
RESULTS
Mosaic and spiral expression patterns of EGFP were observed in young and adult bitransgenic Krt12Cre/+/ZEG mice, respectively. Immunostaining revealed that Cre- cells were also Krt12 negative in the corneal epithelia of Krt12Cre/-/ZAP mice. Using FACS analysis, 60% to 70% of the corneal epithelial cells from Krt12Cre/+/ROSAEGFP mice were EGFP positive, whereas 20% to 30% were negative. RT-PCR revealed that EGFP+ cells express both Krt12Cre and Krt12+ alleles, whereas EGFP- cells express only Krt12+. In the Krt12Cre/- cornea, the number of epithelial cells expressing Cre is the same as that found in Krt12Cre/Cre, which can be explained by the fragility of corneal epithelial cells that did not produce Krt12 because the Krt12Cre allele was not transcribed.
CONCLUSIONS
These observations are consistent with the notion that clonal limbal stem cells randomly activate Krt12 alleles in the process of terminal differentiation. The authors suggest that this selection is advantageous for retaining epithelial cells expressing the Krt12+ allele and that it allows tolerance to structural mutations of Krt12. | 10.1167/iovs.10-5331 |
pubmed_210_21157 | Energy-dependent translational throttle A (EttA) from Escherichia coli is a paradigmatic ABC-F protein that controls the first step in polypeptide elongation on the ribosome according to the cellular energy status. Biochemical and structural studies have established that ABC-F proteins generally function as translation factors that modulate the conformation of the peptidyl transferase center upon binding to the ribosomal tRNA exit site. These factors, present in both prokaryotes and eukaryotes but not in archaea, use related molecular mechanisms to modulate protein synthesis for heterogenous purposes, ranging from antibiotic resistance and rescue of stalled ribosomes to modulation of the mammalian immune response. Here, we review the canonical studies characterizing the phylogeny, regulation, ribosome interactions, and mechanisms of action of the bacterial ABC-F proteins, and discuss the implications of these studies for the molecular function of eukaryotic ABC-F proteins, including the three human family members. | 10.1002/1873-3468.13984 |
pubmed_254_25061 | An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research. | 10.1038/s41380-020-01007-8 |
pubmed_101_24974 | BACKGROUND
The nitrogen-containing polysaccharide chitin is the second most abundant biopolymer on earth and is found in the cell walls of diatoms, where it serves as a scaffold for biosilica deposition. Diatom chitin is an important source of carbon and nitrogen in the marine environment, but surprisingly little is known about basic chitinase metabolism in diatoms.
RESULTS
Here, we identify and fully characterize 24 chitinase genes from the model centric diatom Thalassiosira pseudonana. We demonstrate that their expression is broadly upregulated under abiotic stresses, despite the fact that chitinase activity itself remains unchanged, and we discuss several explanations for this result. We also examine the potential transcriptional complexity of the intron-rich T. pseudonana chitinase genes and provide evidence for two separate tandem duplication events during their evolution.
CONCLUSIONS
Given the many applications of chitin and chitin derivatives in suture production, wound healing, drug delivery, and other processes, new insight into diatom chitin metabolism has both theoretical and practical value. | 10.1186/s12870-021-02849-2 |
pubmed_27_22177 | Recent evidence indicates that nitric oxide participates in the modulation of vascular tone in a variety of vascular beds, including the parenchymal microvasculature of the brain. The present study examined the role of protein kinase activity in the induction and maintenance of the contractile response when endogenous nitric oxide production is inhibited in parenchymal microvessels of the rat hippocampus. Microvessels in in vitro slices of the hippocampus were monitored using computer-assisted video microscopy. The effects of inhibitors of two kinases, protein kinase C and calcium/calmodulin-dependent protein kinase, on the vasoconstrictor response to NG-nitro-L-arginine (L-NNA) were investigated. The resting luminal diameter of the microvessels examined in this study ranged from 9 to 29 microns. Addition of 100 microM L-NNA to the medium superfusing the slice constricted microvessels by 38.8 +/- 0.6%. The addition of protein kinase inhibitors reversed this constriction in a dose-dependent manner. H-7 (50 microM), a relatively non-selective protein kinase C inhibitor, elicited an 81.4 +/- 10.0% reversal of the L-NNA-induced constriction. Bisindolylmaleimide (5 microM), a selective protein kinase C inhibitor, reversed the constriction by 69.1 +/- 13.7%. KN-62, an inhibitor of calcium/calmodulin-dependent protein kinase II, elicited a smaller yet statistically significant reversal of 17.1 +/- 5.1%. Pretreatment with H-7 or bisindolyl-maleimide blocked the LNNA-induced constriction entirely, while KN-62 did not significantly inhibit the response. These findings indicate that the contractile response observed upon removal of endogenous nitric oxidergic vasodilation is mediated by protein kinase activity, and the contribution of protein kinase C to this effect is greater than that of calcium/calmodulin-dependent protein kinase II. The results suggest that a tonic nitric oxidergic influence serves to mask the potential for protein kinase C-mediated vasoconstriction in cerebral microvessels. | 10.1016/0306-4522(96)00158-3 |
pubmed_354_11055 | BACKGROUND
There is a paucity of research concerning paediatric dental consultations in primary care. This is potentially due to the difficulty of measuring the communication behaviours in the complex triadic consultations. The present study aims to describe the development and refinement of a coding scheme to record the triadic communication between dental professionals, child patients and parents.
METHODS
The PaeD-TrICS was developed from video observation of triadic communications and refined through an iterative process. Its practical applicability was assessed via implementation of the scheme on specialised behavioural coding software. Reliability was calculated using Cohen's Kappa.
RESULTS
The PaeD-TrICS contains 45 codes. Forty-four dental professional-child-parent communications were successfully coded through administering the scheme on The Observer XT 10.5 system. Cohen's Kappa was 0.83 (inter-coder) and 0.90 (intra-coder). "Parental verbal facilitation" (mean = 1.68/min) was the most frequent behaviour. Dental professionals' "dentally engaging talk" (mean = 1.24/min), "praise" (mean = 1.10/min) and "instruction" (mean = 0.62/min) were frequently seen. Children's common behaviours included "speech other" (mean = 0.66/min) and non-verbal behaviour i.e. "non-verbal agreement" and verbal behaviour "speech yes" (mean = 0.26/min).
CONCLUSIONS
The PaeD-TrICS is developed to capture the communication behaviour of the triadic consultations in a preventive dental setting. It demonstrates satisfactory intra- and inter-coder reliability and has been successfully used in paediatric dental consultations. | 10.1186/s12903-019-0836-z |
pubmed_1034_17858 | OBJECTIVES
Henoch-Schonlein Purpura (HSP) is the most widespread systemic vasculitis during childhood. Gastrointestinal tract retention and gastrointestinal bleeding are among its major complications. Neutrophil-Lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are indicators related to inflammatory diseases. This study evaluated the relationship between NLR or PLR and gastrointestinal bleeding in HSP.
METHODS
The study consisted of 119 patients and 40 healthy children in the same age group. White Blood Cell (WBC) count, hemoglobin level, platelet count, mean platelet volume (MPV), neutrophil count and lymphocyte count were recorded. The NLR and PLR were calculated based on the results of complete blood count tests performed during the first visit to the hospital.
RESULTS
The average neutrophil count and NLR of the patients with HSP were found to be significantly increased compared to the control group (P = 0.0001). No significant difference was observed between the PLR average of HSP and control groups (P = 0.053). Platelet count average (P = 0.0001) and PLR (P = 0.001) of the patients with gastrointestinal system (GIS) bleeding were found to be statistically significantly increased compared to those who did not have gastrointestinal bleeding. No significant difference was found in the NLR of the patients with and without gastrointestinal bleeding (P = 0.060).
CONCLUSIONS
While the NLR was significantly increased in patients with HSP in this study, the PLR was found to be more significant in patients with gastrointestinal bleeding. Similar to NLR, PLR may also be used as an inflammatory indicator among children with HSP, who have gastrointestinal bleeding. | 10.5812/ijp.8191 |
pubmed_115_7237 | Desorption electrospray ionization (DESI) mass spectrometry is applied to the in situ detection of alkaloids in the tissue of poison hemlock (Conium maculatum), jimsonweed (Datura stramonium) and deadly nightshade (Atropa belladonna). The experiment is carried out by electrospraying micro-droplets of solvent onto native or freshly-cut plant tissue surfaces. No sample preparation is required and the mass spectra are recorded under ambient conditions, in times of a few seconds. The impact of the sprayed droplets on the surface produces gaseous ions from organic compounds originally present in the plant tissue. The effects of operating parameters, including the electrospray high voltage, heated capillary temperature, the solvent infusion rate and the carrier gas pressure on analytical performance are evaluated and optimized. Different types of plant material are analyzed including seeds, stems, leaves, roots and flowers. All the previously reported alkaloids have been detected in C. maculatum, while fifteen out of nineteen known alkaloids for D. stramonium and the principal alkaloids of A. belladonna were also identified. All identifications were confirmed by tandem mass spectrometry. Results obtained show similar mass spectra, number of alkaloids, and signal intensities to those obtained when extraction and separation processes are performed prior to mass spectrometric analysis. Evidence is provided that DESI ionization occurs by both a gas-phase ionization process and by a droplet pick-up mechanism. Quantitative precision of DESI is compared with conventional electrospray ionization mass spectrometry (after sample workup) and the RSD values for the same set of 25 dicotyledonous C. maculatum seeds (one half of each seed analyzed by ESI and the other by DESI) are 9.8% and 5.2%, respectively. | 10.1039/b511161g |
pubmed_916_15173 | BACKGROUND
NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved.
METHODS
Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21(CIP1/WAF1) were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool.
RESULTS
We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell-specific effects. In addition, proteome analysis of NBPF1-overexpressing DLD1 cells identified 32 differentially expressed proteins, of which several are implicated in carcinogenesis.
CONCLUSIONS
We demonstrated that NBPF1 exerts different tumor suppressive effects, depending on the cell line analyzed, and provide new clues into the molecular mechanism of the enigmatic NBPF proteins. | 10.1186/s12885-015-1408-5 |
pubmed_223_9851 | Vascular malformations classification may pose a diagnostic challenge for physicians. In the early stages, they are diagnosed clinically mainly by visual inspection. For a deeper analysis, Doppler ultrasonography is the preferred technique to determine the haemodynamic behaviour of the anomaly. However, this imaging method is not always available and it requires trained operators to acquire and interpret the images. There is a lack of portable and user-friendly systems that may help physicians in the assessment of vascular malformations. We propose a new diagnostic procedure, more affordable and easier to use, based on a portable thermal camera. This technique provides information about temperature, which has been found to be correlated with the flow rate of the lesion. In our study, > 60 vascular malformations of previously diagnosed patients were analysed with a thermal camera to classify them into low-flow and high-flow malformations. The value was 1 for both sensitivity and specificity of this technique. | 10.1111/ced.14346 |
pubmed_45_2335 | The objective of the present study was to evaluate the respiratory effects of cannabinoids and their influence on cardiovascular homeostasis.In spontaneously breathing urethane-anaesthetised rats, intravenous injection of the two synthetic cannabinoid receptor agonists WIN55212-2 and CP55940 strongly and dose-dependently lowered mean arterial pressure, heart rate and the plasma noradrenaline concentration. The cardiovascular depressive effects were associated with a large decrease in respiratory rate, hypoxia, hypercapnia and blood acidosis. All depressor effects of WIN55212-2 were abolished by the selective CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia elicited by WIN55212-2 was inhibited by the muscarinic acetylcholine receptor antagonist methylatropine. The natural agonist Delta(9)-tetrahydrocannabinol also elicited cardiovascular and respiratory depression. In contrast, WIN55212-3, an enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect. The cannabinoid-evoked decreases in blood pressure and heart rate were much more pronounced in spontaneously breathing than in artificially ventilated urethane-anaesthetised rats. In contrast, the plasma noradrenaline concentration was lowered equally in both preparations. Our results show that activation of CB(1) cannabinoid receptors not only induces cardiovascular depression, but also markedly impairs ventilation. The second major finding of the present study is that the respiratory depression evoked by cannabinoids largely amplifies the cardiovascular depression. | 10.1007/s00210-003-0787-3 |
pubmed_512_4827 | BACKGROUND
A prospective randomized study was used to compare surgery times for laparoscopic ovariectomy and salpingectomy in female African lion (Panthera leo) (n = 14) and cheetah (Acinonyx jubatus) (n = 20) and to compare the use of a multiple portal access system (MPAS) and single portal access system (SPAS) between groups. Two different portal techniques were used, namely MPAS (three separate ports) in lions and SPAS (SILS™ port) in cheetahs, using standard straight laparoscopic instruments. Portal access system and first ovary was not randomized. Five different surgery times were compared for the two different procedures as well as evaluating the use and application of MPAS and SPAS. Carbon dioxide volumes for lions were recorded.
RESULTS
In adult lionesses operative time (OPT) (P = 0.016) and total surgical time (TST) (P = 0.032) were significantly shorter for salpingectomy compared to ovariectomy. Similarly in cheetahs OPT (P = 0.001) and TST (P = 0.005) were also shorter for salpingectomy compared to ovariectomy. In contrast, in lion cubs no difference was found in surgery times for ovariectomy and salpingectomy. Total unilateral procedure time was shorter than the respective bilateral time for both procedures (P = 0.019 and P = 0.001) respectively and unilateral salpingectomy was also faster than unilateral ovariectomy (P = 0.035) in cheetahs. Port placement time, suturing time and TST were significantly shorter for SPAS compared to MPAS (P = 0.008). There was, however, no difference in OPT between SPAS and MPAS. Instrument cluttering with SPAS was found to be negligible. There was no difference in mean volume CO2 required to complete ovariectomy in lions but the correlation between bodyweight and total volume of CO2 in lions was significant (rs = 0.867; P = 0.002).
CONCLUSIONS
Laparoscopic salpingectomy was faster than ovariectomy in both adult lions and cheetahs. Using SPAS, both unilateral procedures were faster than bilateral procedures in cheetahs. Placement and suturing of SPAS in cheetahs was easier and faster compared to three separate ports in lions and lion cubs. The use of standard straight instruments during SPAS did not prolong surgery. Surgery was faster in cubs and CO2 required for laparoscopic sterilization in lions could be determined. Predictable surgery times and CO2 volumes will facilitate the accurate planning and execution of surgery in lions and cheetahs. | 10.1186/s13028-016-0199-2 |
pubmed_920_12600 | Research on the impact of the COVID-19 pandemic on communication on Tinder is presented in this article. This research examines reported changes in communication about sex and health during COVID-19 and the potential implications of those changes on hookup culture and sexual health communication beyond the pandemic. Data from 29 in-depth qualitative interviews with 20 female and 9 male college students are reported. Results include discussion of how college students are managing uncertainty, particularly uncertainty about health status, changes in communication and information-seeking strategies, different COVID-19 safety measures they have employed, and the future impact on communication about sexual health post-COVID-19. Participants in this study use uncertainty reduction communication strategies to gauge whether the risks of remaining on Tinder or meeting in person are worth the benefit. Results show that the quality and quantity of communication around first time in-person meetings have been modified, as the traditional public spaces for meeting have been reduced or eliminated and replaced by private spaces. Participants stated that they communicate more frequently and more directly about health, sexual health, and infection transmission. Finally, results indicate that participants have a strong desire to be more cautious and cognizant of health and safety in the future by using some of the communication strategies they developed during COVID-19. | 10.1089/cyber.2020.0685 |
others_285_4094 | and Aims. Diet and lifestyle in school-age children have a particularly large impact on health, as well as various consequences in future. The objective of this papers it to assess the relationship between lifestyle and daily diet and the effects of an unhealthy diet. Material and Methods. An observational cohort study was conducted in Bucharest, in three schools and one high school on 100 children, between 2011 and 2013. The criterion for inclusion was the appropriate age (school-age). The protocol consisted in clinical examination, body mass index (BMI) calculation, questions about diet, physical activity and time spent watching television (TV). Results. Most children do not respect a schedule of meals and snacks (78%). Unhealthy diet (fast food, carbonated beverages, chocolate) registered higher preferences. Mean TV time was 2.32 hours/day (SD=1.92) and a strong evidence on relationship between age and number of hours allocated to TV was discovered (p<.01). Four percent of children were found to be under the 5th percentile (underweight), 18% between 85th and 95th percentile (overweight) and 14% above 95th percentile (obesity). Conclusions. A sedentary life in this case was mainly determined by the time spent daily in front of the television rather than lack of exercise. © 2015 ILEX PUBLISHING HOUSE, Bucharest, Rouman | 10.1515/rjdnmd-2015-0030 |
pubmed_448_11862 | Novel Fe3O4@C@MnO2 composites were successfully synthesized for the first time via an interfacial reaction between magnetic porous carbon and KMnO4, in which the magnetic porous carbon was derived from the pyrolysis of Fe-MIL-88A under N2 atmosphere. Interestingly, the obtained Fe3O4@C@MnO2 composites were found to have triple-enzyme mimetic activity including peroxidase-like, catalase-like, and oxidase-like activity. As a peroxidase mimic, Fe3O4@C@MnO2 composites could catalyze the oxidation of TMB into a blue oxidized product by H2O2. As a catalase mimic, Fe3O4@C@MnO2 could catalyze the decomposition of H2O2 to generate O2 and H2O. As an oxidase mimic, Fe3O4@C@MnO2 could catalyze the direct oxidation of TMB to produce a blue oxidized product without H2O2. Reactive oxygen species measurements revealed that the oxidase-like activity originated from 1O2 and O2-∙and little∙OH generated by the dissolved oxygen, which was catalyzed by the Fe3O4@C@MnO2 in the TMB oxidation reaction. The oxidase-like activity of Fe3O4@C@MnO2 was investigated in detail. Under the optimized conditions, a rapid, sensitive, visual colorimetric method for dopamine detection was developed based on the inhibitory effect of dopamine on the oxidase-like activity. The proposed method allows for dopamine detection with a limit of detection of 0.034 μM and a linear range of 0.125-10 μM. This new colorimetric method was successfully used for the determination of dopamine in human blood samples. | 10.1007/s00604-021-05114-3 |
pubmed_578_5468 | This study evaluates 3 selective media (Pylori agar [bioMérieux, France], BD Helicobacter agar, modified [Becton Dickinson, USA], and an in-house medium) designed for Helicobacter pylori isolation. Ninety-eight strains were isolated from 400 gastric biopsies. The media were equally efficient for Helicobacter pylori's growth. However, contaminations were only observed using commercial media. | 10.1016/j.diagmicrobio.2010.08.009 |
pubmed_315_16400 | Starting from a vinylepoxide, a short and practical synthesis of D-erythro-sphingosine is described. The key transformations are a regioselective opening of the vinylepoxide and an E-selective cross-metathesis, affording the target molecule 5 in steps and 51% overall yield. | 10.1039/b403568b |
pubmed_50_19811 | MOTIVATION
Gene annotation and pathway databases such as Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes are important tools in Gene-Set Test (GST) that describe gene biological functions and associated pathways. GST aims to establish an association relationship between a gene-set of interest and an annotation. Importantly, GST tests for over-representation of genes in an annotation term. One implicit assumption of GST is that the gene expression platform captures the complete or a very large proportion of the genome. However, this assumption is neither satisfied for the increasingly popular boutique array nor the custom designed gene expression profiling platform. Specifically, conventional GST is no longer appropriate due to the gene-set selection bias induced during the construction of these platforms.
RESULTS
We propose bcGST, a bias-corrected GST by introducing bias-correction terms in the contingency table needed for calculating the Fisher's Exact Test. The adjustment method works by estimating the proportion of genes captured on the array with respect to the genome in order to assist filtration of annotation terms that would otherwise be falsely included or excluded. We illustrate the practicality of bcGST and its stability through multiple differential gene expression analyses in melanoma and the Cancer Genome Atlas cancer studies.
AVAILABILITY AND IMPLEMENTATION
The bcGST method is made available as a Shiny web application at http://shiny.maths.usyd.edu.au/bcGST/.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online. | 10.1093/bioinformatics/bty783 |
pubmed_34_8138 | Beta-actin is commonly used to normalize molecular expression studies due to its high conservation as an endogenous housekeeping gene. However, recent studies have shown that beta-actin expression can change in response to biochemical stimuli, during growth and differentiation, and in disease states. As can be expected, these phenomena substantially compromise the use of beta-actin as an internal reference marker. Under these conditions, varying expression of beta-actin likely indicates changed function for this maintenance molecule. Further studies exploring the function of actin in these environments will probably lead to a new integrative understanding of the roles of this housekeeping gene. | 10.1016/j.cca.2007.07.003 |
pubmed_157_8273 | BACKGROUND
After a successful trabeculectomy, a sudden intraocular pressure decrease may alter the intracranial to intraocular pressure ratio and cause decompression retinopathy. Frequent Valsalva maneuvers may also play a role in its pathogenesis. This condition may manifest as multiple retinal hemorrhages, edema of the optic disc, macular edema, or a sudden decrease in visual acuity postoperatively. Outcomes for patients are usually good, with spontaneous resolution occurring within a matter of weeks. It has been rarely reported in the literature as a bilateral condition.
CASE PRESENTATION
We present a case of consecutive bilateral decompression retinopathy in a 54-year-old severely obese Caucasian woman (body mass index 37 kg/m(2)) with open angle glaucoma and a poor history of medical therapeutic compliance, who chose surgical treatment based on her inability to consistently use ocular drops. Our patient underwent a trabeculectomy with mitomycin C in both eyes, with surgeries taking place 3 months apart. After the first surgery, 2 weeks postoperatively, she complained of decreased visual acuity. Examination of her right eye fundus revealed multiple retinal hemorrhages and disc edema. There was a similar pattern in her left eye, this time including maculopathy. Her visual acuity and fundoscopic changes resolved spontaneously over a period of a month in both cases. Currently, our patient has well-controlled bilateral intraocular pressure, ranging between 14 and 16 mmHg, without hypotensive medication.
CONCLUSIONS
Decompression retinopathy is a potential complication after glaucoma surgery, but has rarely been described as a bilateral consecutive condition. A comprehensive approach could help to anticipate its occurrence and manage it. | 10.1186/s13256-016-0814-x |
others_127_15079 | The continuous epitopes of Candida albicans proteinase SAP 2 were derived by epitope mapping with sera from patients with oral candidiasis (n = 3) necropsy-proven disseminated candidiasis (n = 5), paired sera from patients who had recovered from blood culture-proven disseminated candidiasis (n = 3) and infection due to Candida parapsilosis (n = 2) and Candida parapsilosis (n = 2). In C. albicans infection, IgM identified epitopes in amino acid positions 57-61 (QAVPV), 146-151 (SQGTLY) and 346-351 (PYDKCQ) and IgG at position 386-390 (VKYTS). For C. tropicalis IgM and IgG were positive for the same epitopes whilst IgG also detected epitopes at 78-83 (SNNQKL) and 159-164 (GVSIKN). For C. parapsilosis, IgM was positive for SNNQKL and IgG detected no epitopes. Reactivity of two of the epitopes as peptides KTSKRQAVPVTL and SLAQVKYTSASSI was confirmed in an indirect ELISA. At a cut-off optical density of 0.4, IgM against either peptide was associated with survival but present in only about half of the sera (n = 60) from patients who recovered from disseminated candidiasis whilst IgG levels were disappointing. Human recombinant antibodies from a patient who had recovered from disseminated candidiasis against either of these peptides had no activity in a lethal mouse model of candidal inf | 10.1016/S0928-8244(97)00076-X |
pubmed_358_3161 | Brush cells are specialised epithelial cells that are assumed to represent chemoreceptors of the digestive tract. They comprise a small population of the epithelial cells lining the intestine, possess a unique ultrastructure and, in many aspects, resemble the receptor cells of taste buds. To characterise glycoconjugates possibly involved in a sensory function, we investigated brush cells in the small intestine of three species using lectin histochemistry in confocal light and thin-section electron microscopy. Brush cells of rats were selectively labelled by the sialic acid-specific lectin Maackia amurensis agglutinin, those of guinea-pigs by the D-galactose-specific lectin Bandeiraea simplicifolia agglutinin, isolectin B4 and those of mice by the L-fucose-specific lectin Ulex europaeus agglutinin lectin I. Lectin binding sites were consistently located in the glycocalyx of the apical membrane and in that of cytoplasmic vesicles. In vivo lectin labelling revealed that the glycoconjugates of the apical membrane are accessible under physiological conditions, that brush cells do not endocytose and that they probably possess a high membrane turnover rate. The results show that specialisations exist in the composition of glycoconjugates forming the glycocalyx of brush cells in all species investigated. The presence of brush cell-specific glycoconjugates would be in accordance with the current hypothesis of a receptive function of brush cells. Differences in the specific glycosylation patterns among rats, guinea-pigs and mice indicate that species-specific adaptations exist. | 10.1007/s004180000148 |
pubmed_1058_20587 | Centromere protein C (CENPC) is a key protein that has been localized to the inner kinetochore plate of active mammalian centromeres. Using gene targeting techniques, we have disrupted the mouse Cenpc gene and shown that the gene is essential for normal mouse embryonic development. Heterozygous mice carrying one functional copy of the gene are healthy and fertile, whereas homozygous embryos fail to thrive. In these embryos, mitotic arrest and gross morphological degeneration become apparent as early as the morula stage of development. The degenerating embryos demonstrate highly irregular cell and nuclear morphologies, including the presence of a large number of micronuclei. Mitotic chromosomes of these embryos display a scattered and often highly condensed configuration and do not segregate in an ordered fashion. These results describing the phenotype of the mutant mouse embryos indicate that CENPC has a direct role in the mitotic progression from metaphase to anaphase. | 10.1073/pnas.95.3.1136 |
pubmed_862_10 | BACKGROUND
Cytokines and alcohol share a common modulation of inflammation and hormones as well as being implicated in multiple diseases, but the mechanisms are poorly understood. The purpose of this study was to investigate the interaction of liver, serum and brain cytokines as well as whether ethanol would potentiate endotoxin (Lipopolysaccharide, LPS) responses once ethanol had cleared.
METHODS
Male C57BL/6J mice were treated intragastrically with water (control) or ethanol (5 g/kg, i.g., 25% ethanol, w/v), with volumes matched, for 1 day or daily for 10 days. Mice were then injected intraperitoneally with saline (control) or LPS (3 mg/kg, i.p.) in saline 24 hrs after the last dose of ethanol. Gene expression and protein synthesis of proinflammatory cytokines and anti-inflammatory cytokine, oxidative enzymes, microglial activation and inhibition of neurogenesis were examined using real-time PCR, ELISA, and immunohistochemistry.
RESULTS
LPS increased proinflammatory cytokines (TNFalpha, MCP-1, IL-1beta) several fold in liver, brain and serum at 1 hr. Ethanol is known to increase liver cytokines and alter the risk of multiple chronic diseases. Ten daily doses of ethanol increased brain and liver TNFalpha, and pretreatment with ethanol potentiated LPS-induced increases in TNFalpha, MCP-1, IL-1beta in liver, serum and brain. Proinflammatory cytokine levels in liver and serum returned to basal levels within a day, whereas brain proinflammatory cytokines remained elevated for long periods. IL-10, an anti-inflammatory cytokine, is reduced in brain by ethanol and LPS, while brain proinflammatory cytokines remain increased, whereas liver IL-10 is increased when proinflammatory cytokines have returned to control levels. Activation of brain microglia indicated by morphological changes, reduced neurogenesis and increased brain expression of COX-2 and gp91phox NADPH oxidase subunit mRNA were found in the 10 daily doses of ethanol-pretreated LPS group.
CONCLUSION
Acute increases in serum cytokines induce long lasting increases in brain proinflammatory cytokines. Ten daily doses of ethanol exposure results in persistent alterations of cytokines and significantly increases the magnitude and duration of central and peripheral proinflammatory cytokines and microglial activation. Ethanol induced differential anti-inflammatory cytokine IL-10 responses in liver and brain could cause long lasting disruption of cytokine cascades that could contribute to protection or increased risk of multiple chronic diseases. | 10.1186/1742-2094-5-10 |
pubmed_824_23790 | BACKGROUND
The number of corneal transplantations has increased in Germany in recent years. One reason is an earlier time point of surgery due to less invasive posterior lamellar grafting techniques. To date, penetrating and lamellar corneal transplantations are the only established therapeutic options to treat corneal diseases resulting from endothelial cell pathologies.
AIM
This review article provides an insight into nanoparticle-related translational strategies to improve or to avoid corneal transplantation.
RESULTS
Nanoparticle-based strategies for optimization of the corneal endothelium have different fields of application: 1. during donor cornea cultivation in culture medium, 2. for single cell injection therapies and 3. to treat the patients' own endothelium in an effort to avoid transplantation.
CONCLUSION
Several translational concepts exist to improve or to avoid grafting of a donor cornea. The coming decade will provide established alternatives to conventional corneal transplantation. | 10.1007/s00347-017-0640-6 |
pubmed_799_7931 | MOTIVATION
Scanning parameters are often overlooked when optimizing microarray experiments. A scanning approach that extends the dynamic data range by acquiring multiple scans of different intensities has been developed.
RESULTS
Data from each of three scan intensities (low, medium, high) were analyzed separately using multiple scan and linear regression approaches to identify and compare the sets of genes that exhibit statistically significant differential expression. In the multiple scan approach only one-third of the differentially expressed genes were shared among the three intensities, and each scan intensity identified unique sets of differentially expressed genes. The set of differentially expressed genes from any one scan amounted to < 70% of the total number of genes identified in at least one scan. The average signal intensity of genes that exhibited statistically significant changes in expression was highest for the low-intensity scan and lowest for the high-intensity scan, suggesting that low-intensity scans may be best for detecting expression differences in high-signal genes, while high-intensity scans may be best for detecting expression differences in low-signal genes. Comparison of the differentially expressed genes identified in the multiple scan and linear regression approaches revealed that the multiple scan approach effectively identifies a subset of statistically significant genes that linear regression approach is unable to identify. Quantitative RT-PCR (qRT-PCR) tests demonstrated that statistically significant differences identified at all three scan intensities can be verified.
AVAILABILITY
The data presented can be viewed at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession no. GSE3017. | 10.1093/bioinformatics/btl270 |
pubmed_170_16395 | We encountered 2 cases of microscopic polyangitis (MPA) with preceding interstitial pneumonia. The patients were elderly men, and radiological findings showed a UIP pattern in both cases. Furthermore, ANCA-associated vasculitis had been suspected since the first admission in case 1, because MPO-ANCA tests were positive, and the surgical lung biopsy revealed vasculitis in a honeycomb lesion. A diagnosis of idiopathic pulmonary fibrosis was made in case 2 because no findings of vasculitis were pathologically confirmed, and MPO-ANCA was not examined. Both patients were followed up without any treatment, but steroid therapy with immunosuppressants was initiated after a diagnosis of MPA was made from a renal failure complication. Remission continued in case 1, but patient 2 died due to a pulmonary hemorrhage complication, despite some temporary improvements. An autopsy revealed massive alveolar hemorrhage and neutrophil infiltration in the alveolar walls that suggested pulmonary capillaritis, in spite of the absence of pathological evidence, which was not detected in the honeycomb lesions. These 2 cases indicate that MPO-ANCA should be examined in the follow-up of chronic interstitial pneumonia. Furthermore, it should be assumed that the size of involved blood vessels, their distribution and the timing of occurrence may be different in individual case of ANCA-associated interstitial pneumonia. | pubmed_170_16395 |
pubmed_879_1618 | During the last decade, the evidences on the relationship between neurodevelopmental disorders and the microbial communities of the intestinal tract have considerably grown. Particularly, the role of gut microbiota (GM) ecology and predicted functions in Autism Spectrum Disorders (ASD) has been especially investigated by 16S rRNA targeted and shotgun metagenomics, trying to assess disease signature and their correlation with cognitive impairment or gastrointestinal (GI) manifestations of the disease. Herein we present a metaproteomic approach to point out the microbial gene expression profiles, their functional annotations, and the taxonomic distribution of gut microbial communities in ASD children. We pursued a LC-MS/MS based investigation, to compare the GM profiles of patients with those of their respective relatives and aged-matched controls, providing a quantitative evaluation of bacterial metaproteins by SWATH analysis. All data were managed by a multiple step bioinformatic pipeline, including network analysis. In particular, comparing ASD subjects with CTRLs, up-regulation was found for some metaproteins associated with Clostridia and with carbohydrate metabolism (glyceraldehyde-3-phosphate and glutamate dehydrogenases), while down-regulation was observed for others associated with Bacteroidia (SusC and SusD family together with the TonB dependent receptor). Moreover, network analysis highlighted specific microbial correlations among ASD subgroups characterized by different functioning levels and GI symptoms. SIGNIFICANCE: To the best of our knowledge, this study represents the first metaproteomic investigation on the gut microbiota of ASD children compared with relatives and age-matched CTRLs. Remarkably, the applied SWATH methodology allowed the attribution of differentially regulated functions to specific microbial taxa, offering a novel and complementary point of view with respect to previous studies. | 10.1016/j.jprot.2021.104407 |
pubmed_1096_22269 | The aleurone layer (AL) is the grain peripheral tissue; it is rich in micronutrients, vitamins, antioxidants, and essential amino acids. This highly nutritive part of the grain has been less studied partly because its isolation is so laborious. In the present study, the ALs of Triticum aestivum (variety Récital) were separated manually at 15 stages of grain development. A total of 327 proteins were identified using 2-DE LC-MS/MS. They were classified in six main groups and 26 sub-groups according to their biochemical function. Proteomic analysis revealed seven different profiles distributed among three main development stages: (i) early AL development, with proteins involved in intense metabolic activities in the growth and development of the cell wall compounds; (ii) the intermediate stage, characterized by oxidative stress and defense proteins (65%) linked with loss of water in peripheral layers during grain filling; and (iii) AL maturation, involving the production of amino acids and the control of reactive oxidative species to enable the accumulation and maturation of globulins within the AL. The present study provides the first insights into developing proteome in the AL. We describe the numerous AL enzymes involved in the accumulation of storage protein and in the protection of the endosperm over time.
BIOLOGICAL SIGNIFICANCE
The hand dissection of wheat aleurone layer (AL) was carried in this study for the first time on fifteen developmental stages from cell differentiation to grain maturity. Three major phases were revealed over AL development: cell division activities, globulins storage, and grain protection. Enzymes related to metabolites and vitamins were abundantly expressed during the two first phases. In parallel to the progressive globulins accumulation, the final phase was characterized by key enzyme synthesis involved in energy production, amino-acids and antioxidant synthesis plus others to face hypoxia and dehydration of grain tissues. | pubmed_1096_22269 |
pubmed_625_15579 | The cellular uptake of mizoribine (MZR), an immunosuppressant, and metabolism of MZR to MZR-5'- monophosphate (MZRP), an active metabolite, were evaluated in L5178Y-R mouse lymphoma cells and peripheral blood mononuclear cells (PBMCs) of rats and kidney transplant recipients (KTRs, n = 22). Real-time PCR analysis revealed the expression of ENT1 and ENT2 mRNAs, but not of CNTs, in L5178Y-R cells and rat's PBMCs. In L5178Y-R cells, the uptake of MZR was suppressed by adenosine, a substrate for ENT1 and ENT2, but not by 5-(4-nitrobenzyl)-6-thioinosine (0.1 μM), an ENT1 inhibitor. Saturable metabolism of MZR to MZRP was observed. In rats, peak plasma concentrations of MZR and peak concentrations of MZR and MZRP in PBMCs were observed 3 h after oral administration. MZR disappeared from PBMCs in parallel with plasma MZR, but the disappearance of MZRP from PBMCs appeared to be slow. In KTRs, the mean plasma concentration of MZR 3-4 h after ingestion was 3.14 μg/ml and the mean MZRP concentration in PBMCs was 16.8% of MZR, reflecting the involvement of ENT in the uptake of MZR. A linear relationship was observed between plasma MZR concentrations ranging from 1 to 6 μg/ml and PBMC's MZRP concentrations ranging from 90 to 200 ng/ml. | 10.1016/j.dmpk.2018.08.007 |
pubmed_1096_8701 | Gut content analysis using molecular techniques can help elucidate predator-prey relationships in situations in which other methodologies are not feasible, such as in the case of trophic interactions between minute species such as mites. We designed species-specific primers for a mite community occurring in Spanish citrus orchards comprising two herbivores, the Tetranychidae Tetranychus urticae and Panonychus citri, and six predatory mites belonging to the Phytoseiidae family; these predatory mites are considered to be these herbivores' main biological control agents. These primers were successfully multiplexed in a single PCR to test the range of predators feeding on each of the two prey species. We estimated prey DNA detectability success over time (DS50), which depended on the predator-prey combination and ranged from 0.2 to 18 h. These values were further used to weight prey detection in field samples to disentangle the predatory role played by the most abundant predators (i.e. Euseius stipulatus and Phytoseiulus persimilis). The corrected predation value for E. stipulatus was significantly higher than for P. persimilis. However, because this 1.5-fold difference was less than that observed regarding their sevenfold difference in abundance, we conclude that P. persimilis is the most effective predator in the system; it preyed on tetranychids almost five times more frequently than E. stipulatus did. The present results demonstrate that molecular tools are appropriate to unravel predator-prey interactions in tiny species such as mites, which include important agricultural pests and their predators. | 10.1111/1755-0998.12409 |
pubmed_660_6024 | OBJECTIVE
To identify the determinants of misconceptions about diabetes in patients registered with a diabetes clinic at a tertiary care hospital in Eastern Saudi Arabia.
MATERIALS AND METHODS
This cross-sectional survey was carried out at a diabetes clinic of a tertiary care hospital in Eastern Saudi Arabia, from January to December 2012. A total of 200 diabetic patients were interviewed using a questionnaire comprising 36 popular misconceptions. The total misconception score was calculated and categorized into low (0-12), moderate (13-24) and high (25-36) scores. The association of misconception score with various potential determinants was calculated using Chi-square test. Step-wise logistic regression was applied to the variables showing significant association with the misconception score in order to identify the determinants of misconceptions.
RESULTS
The mean age was 39.62 ± 16.7 and 112 (56%) subjects were females. Type 1 diabetics were 78 (39%), while 122 (61%) had Type 2 diabetes. Insulin was being used by 105 (52.5%), 124 (62%) were self-monitoring blood glucose and 112 (56%) were using diet control. Formal education on diabetes awareness had been received by 167 (83.5%) before the interview. The mean misconception score was 10.29 ± 4.92 with 115 (57.5%) subjects had low misconception scores (<12/36). On the Chi-square test, female gender, rural area of residence, little or no education, <5 or >15 years since diagnosis, no self-monitoring, no dietary control and no diabetes education were all significantly (P < 0.05) associated with higher misconception scores. Step-wise logistic regression suggested that diabetes education, gender, education and time since diagnosis were significant (P < 0.05) predictors of misconception scores.
CONCLUSIONS
The strongest determinants of misconceptions about diabetes in our study population were female gender, rural area of residence, illiteracy or little education, <5 or >15 years since diagnosis, no self-monitoring, no diet control and no education about diabetes. | 10.4103/2230-8229.134764 |
pubmed_609_2761 | Patel analysed a two-period cross-over design with baseline measurements assuming bivariate normality for the joint distribution of the period responses. In this paper, we propose non-parametric methods for analysing this design, including the use of the Wilcoxon rank sum test to derive the preliminary tests from the baseline measurements. We fit a robust regression line of the treatment response on baseline for each period and compute residuals. We also fit a robust locally weighted regression as an alternative method for computing residuals. Then, following Koch's procedure, we analyse the residuals for testing the significance of the treatment x period interaction and the treatment difference. We provide a numerical example to illustrate the methods. | 10.1002/(SICI)1097-0258(19960130)15:2<117::AID-SIM158>3.0.CO;2-B |
pubmed_153_15845 | We describe a-2-year-old boy who presented with a neonatal history of thrombocytopenia associated with a constellation of limb malformations mimicking split hand/foot malformation with long bone deficiency (SHFLD) syndrome. Limb malformations consisted of unilateral monodactyly with radial aplasia, unilateral split foot and bilateral club foot. Tibial aplasia of one limb and tibial hypoplasia of the other limb were notable. Partial agenesis of the sacrum was additional skeletal malformation. Craniofacial features included dense thick scalp hair, narrow frontal area, thick eye-brows, deep-set eyes, depressed nasal bridge, and small overhanging nasal tip, full-cheeks, and large ears. Array-CGH showed duplication of the short arm of chromosome 17p13.3 in the boy and his father, respectively. The father was free from any skeletal abnormalities, though he shares similar craniofacial dysmorphic features like his son. In addition, a paternal sib (uncle of the proband) manifested a phenotype similar to that of the proband. To the best of our knowledge the overall phenotypic and genotypic characterizations were consistent but not completely compatible with the traditional type of TAR syndrome or with SHFLD syndrome. We report on what might be a novel variant of SHFLD associated with transient thrombocytopenia, dysmorphic facial features, and a constellation of bone malformations. | 10.1002/ajmg.a.36614 |
pubmed_940_13403 | A gas chromatographic-mass spectrometric (GC-MS) assay was developed for the quantitative analysis of methyl salicylate (MeS), ethyl salicylate (ES) and salicylic acid (SA) from biological fluids. The method was validated from 100-microl rat liver homogenate preparations (5 mg/ml protein) in 70 mM KH2PO4 (pH 7.4) buffer and from 100 microl rat plasma. The samples were extracted with chloroform, derivatized with BSTFA and quantitated by GC-MS in the SIM mode. The standard curves ranged from 31 ng/ml to 800 or 1250 ng/ml. Relative standard deviations and bias were less than 11% in plasma and homogenate for all compounds except SA which evidenced greater variability. The assay was used in preliminary experiments to characterize the pharmacokinetics of MeS in rats. | 10.1016/s0378-4347(98)00348-x |
pubmed_1093_14416 | Uterine leiomyoma, a benign tumor, may be treated with drugs, albeit surgical resection is more common. The present study aimed to evaluate the treatment of leiomyoma cases by uterine artery embolization (UAE) using a gelatin sponge prepared by the pumping method. The results of 700 leiomyoma cases treated by UAE in the outpatient department were evaluated. UAE was performed by injecting gelatin sponge prepared by the pumping method into the uterine artery. Among 700 cases, effective cases were 680 (97.2%), ineffective cases were 18 (2.8%) and impossible cases for UAE were 2 (0.2%). Retreatment was required in 23 cases (3.3%). Complication events designated by the Society of Interventional Radiology Clinical Practice Guidelines occurred in 31 cases (4.4%): 1 case showed permanent adverse sequelae, 4 cases required major therapy with a prolonged hospitalization (>48 h) and 10 patients required therapy with minor hospitalization (<48 h). The remaining 16 cases required nominal or no therapy. Follow-up of patients was performed for 599 cases for an average period of 1.2±0.9 years, ranging between 1 month and 6 years. Pregnancy after UAE was observed in 12 cases/15 cycles. Thus, the findings indicate that UAE using gelatin sponge prepared by the pumping method applied to outpatients is a safe and useful treatment procedure. | 10.3892/etm.2012.688 |
pubmed_643_13320 | This paper is a commentary on the training of Chinese Primary Health Care Doctors to reduce chronic illness and its burden. First, we will consider the policy position of the Chinese government concerning the development of a competent and enlarged primary physician workforce to deliver the proposed primary health care system reforms. We then turn to a review of the drivers of the high burden of chronic illnesses especially in older people in China. We argue that the curriculum for the training of primary health care medical practitioners should match the demonstrated high prevalence chronic illnesses and their risk factors and that there needs to specific competencies in prevention and mitigation of the diseases and their risk factors. | 10.3389/fpubh.2019.00168 |
pubmed_72_19159 | This study examined the effects of antismoking ads on Korean adult male smokers. An experiment was conducted to explore how message framing and visual-fear appeals embedded in antismoking ads may influence ad-evoked fear, threat appraisals, and intention to quit smoking. Results showed that (a) antismoking ad exposure increased ad-evoked fear and cessation intention; (b) optimistic bias was stronger when the visual-fear appeal was absent in antismoking ads; and | 10.1080/10810730.2015.1012242 |
pubmed_759_2535 | Serum prolactin (PRL) and thyrotropin (TSH) levels were measured after iv administration of 200 microng of synthetic thyrotropin-releasing hormone (TRH) in 20 normal women ages 18 to 34. Ten women received TRH on days 7 to 8 of the menstrual cycle and 10 women received TRH on days 21-22. Although there was no difference in the dose of TRH relative to body weight in the two groups of women, the peak PRL level after TRH stimulation was greater in the women studied on day 21-22 (48.5+/-5.7 ng/ml, mean+/-SE) than on day 7-8 (35.2+/-4.2 ng/ml) of the cycle (P less than 0.05). In contrast, TSH rose to a greater degree in the preovulatory phase (13.8+/-1.8 micronU/ml) than the luteal phase (7.7+/-0.7 micronU/ml of the cycle (P less than .01). Studies of the PRL and TSH response after TRH administration should take the phase of the menstrual cycle into account. | 10.1210/jcem-44-5-985 |
pubmed_644_18775 | We have examined the possible role of extracellular reduction-oxidation (redox) state in regulation of biological/biochemical features associated with prostate cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1-NB26) cell lines were used for the present in vitro analysis. Increasing levels of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in cell invasion ability, whereas increasing levels of extracellular superoxide radical (O(2)(*-)) using xanthine/xanthine oxidase resulted in an increase in cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an increased glutathione/glutathione disulfide ratio in the medium in comparison with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells), suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We hypothesized that O(2)(*-) production at or near the plasma membrane or in the adjacent extracellular matrix at least partially regulated prostate cancer cell invasion. Using adenovirus-mediated extracellular superoxide dismutase (EC-SOD) gene transduction to enzymatically decrease O(2)(*-) levels, we showed that in the presence of heparin, adenovirus EC-SOD gene transduction resulted in an increase in the expression of EC-SOD outside the cells with resultant inhibition of cell invasion ability. This inhibition correlated with reduced metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP] activities and increased levels of extracellular nitrite. Our results suggest a prominent role of extracellular redox status in regulation of cell invasion, which may provide opportunities for therapeutic interventions. | 10.1158/0008-5472.CAN-08-0162 |
pubmed_378_12719 | The intravenous immunoglobulin infusion therapy (IVIg) has recently acquired an important role in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Some patients, however, require repetitive infusions to maintain the improvement. We planned a one-day therapy with 0.4 g/kg of IVIg in every 7 or 10 days for two CIDP patients who had required a 5-day course of IVIg in every month because of frequent exacerbations. Serum levels of IgG in both patients were kept as high as 2,000 mg/dl resulting in maintaining the improvement without any side effects. | pubmed_378_12719 |
pubmed_41_12113 | We present and compare several many-body methods as applied to two-dimensional quantum dots with circular symmetry. We calculate the approximate ground state energy using a harmonic oscillator basis optimized by Hartree-Fock (HF) theory and further improve the ground state energy using two post-HF methods: in-medium similarity renormalization group and coupled cluster with singles and doubles. With the application of quasidegenerate perturbation theory or the equations-of-motion method to the results of the previous two methods, we obtain addition and removal energies as well. Our results are benchmarked against full configuration interaction and diffusion Monte Carlo where available. We examine the rate of convergence and perform extrapolations to the infinite basis limit using a power-law model. | 10.1063/1.4995615 |
pubmed_711_14259 | The use of the peroxidase-anti-peroxidase (PAP) technique has been described previously for the detection of cellular antigens and in particular ABO antigens from tissue samples (Pedal and Hülle 1984; Pedal and Baedeker 1985; Pedal et al. 1985). In this survey, the PAP method has been employed to study the detection of ABO antigens in cells from body fluids of particular interest to forensic science, namely buccal cells and vaginal cells. Also tested, but in a limited number, were mixtures of body fluids and semen samples. No false reactions were obtained from buccal cells, all samples corresponding to the ABO blood type of the donor. Preliminary results from vaginal cells, vaginal/buccal cell mixtures, and semen were encouraging but must be treated with caution due to the limited number tested. Vaginal smears contaminated with semen showed varying degrees of nonspecificity. | 10.1007/BF00198627 |
pubmed_670_8990 | A 57-year-old male was admitted with pulsatile tinnitus and hearing disturbance of the right ear and right peripheral facial palsy. Otological examination revealed a pulsatile red mass in his right ear and right conductive hearing disturbance. CT and MRI showed the mass lesion at his right middle fossa near the geniculate ganglion. Right external carotid angiogram disclosed a tumor stain fed by the middle meningeal artery. The tumor was removed via a combination of subtemporal and transmastoidal approaches. Histologically, this tumor was diagnosed as angiomatous meningioma partly with meningotheliomatous meningioma. Meningioma in this region is very rare. We discussed its clinical and radiological characteristics in comparison with chemodectoma and facial neurinoma at the geniculate ganglion. | pubmed_670_8990 |
pubmed_1142_15687 | The spontaneous aggregation and poor electronic conductivity are widely recognized as the main challenges for practically applied nano-sized tin dioxide-based anode candidates in lithium-ion batteries. This work describes a hierarchical graphite and graphene oxide (GO) framework stabilized tin dioxide quantum dot composite (SnO2@C/GO), which is synthesized by a solid-state ball-milling treatment and a water-phase self-assembly process. Characterization results demonstrate the engineered inside nanostructured graphite and outside GO layers from the SnO2@C/GO composite jointly contribute to a good immobilization effect for the SnO2 quantum dots. The hierarchical carbonaceous matrix supported SnO2 quantum dots could maintain good structure stability over a long cycling life under high current densities. As an anodic electrochemically active material for lithium-ion batteries, the SnO2@C/GO composite shows a high reversible capacity of 1156 mAh·g-1 at the current density of 1000 mA·g-1 for 350 continual cycles as well as good rate performance. The large pseudocapacitive behavior in this electrode is favorable for promoting the lithium-ion storage capability under higher current densities. The whole synthetic route is simple and effective, which probably has good potential for further development to massively fabricate high-performance electrode active materials for energy storage. | 10.1016/j.jcis.2021.05.070 |
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