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pubmed_781_22948
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A major therapeutic obstacle in clinical oncology is intrinsic or acquired resistance to therapy, leading to subsequent relapse. We have previously shown that systemic administration of different cytotoxic drugs can induce a host response that contributes to tumor angiogenesis, regrowth and metastasis. Here we characterize the host response to a single dose of local radiation, and its contribution to tumor progression and metastasis. We show that plasma from locally irradiated mice increases the migratory and invasive properties of colon carcinoma cells. Furthermore, locally irradiated mice intravenously injected with CT26 colon carcinoma cells succumb to pulmonary metastasis earlier than their respective controls. Consequently, orthotopically implanted SW480 human colon carcinoma cells in mice that underwent radiation, exhibited increased metastasis to the lungs and liver compared to their control tumors. The irradiated tumors exhibited an increase in the colonization of macrophages compared to their respective controls; and macrophage depletion in irradiated tumor-bearing mice reduces the number of metastatic lesions. Finally, the anti-tumor agent, dequalinium-14, in addition to its anti-tumor effect, reduces macrophage motility, inhibits macrophage infiltration of irradiated tumors and reduces the extent of metastasis in locally irradiated mice. Overall, this study demonstrates the adverse effects of local radiation on the host that result in macrophage-induced metastasis.
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10.18632/oncotarget.4826
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pubmed_198_10978
|
This in vivo investigation determined the relative potentials of 7 C3H/He and C3Hf/He mammary tumors and their metastases to metastasize spontaneously from intramammary implants. The purpose of the studies was to examine the hypothesis that metastases derive from distinct sub-populations of cells in primary tumors which have specific inheritable characteristics that predispose the cells to form metastases. By serially transplanting, in parallel tests, tissue from autochthonous metastases and tissue from autochthonous primary tumors, the distinction of tumor-cell populations with different metastatic potentials was anticipated. However, the results of the experiments showed that primary tumors and metastases in autochthonous hosts had similar potentials for spontaneous metastasis. Moreover, the primary tumors and the metastases, transplanted as parallel lines through consecutive generations, maintained similar average metastasizing potentials. Changes in metastatic potential which occurred in 3 of the 7 tumors during serial passage appeared in nearly equal transplant generations in the parallel lines of the primary tumor and the metastases. The data suggest that the spontaneous metastases were not derived from a sub-population of cells with inheritable high metastasizing potential, but developed through stochastic events from the average tumor cells that entered the circulation.
|
10.1002/ijc.2910410614
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pubmed_163_22147
|
The interconnected and overlapping habitats present in natural ecosystems remain a challenge in determining the forces driving microbial community composition. The cuplike leaf structures of some carnivorous plants, including those of the family Sarraceniaceae, are self-contained ecological habitats that represent systems for exploring such microbial ecology questions. We investigated whether Sarracenia minor and Sarracenia flava cultivate distinct bacterial communities when sampled at the same geographic location and time. This sampling strategy eliminates many abiotic environmental variables present in other studies that compare samples harvested over time, and it could reveal biotic factors driving the selection of microbes. DNA extracted from the decomposing detritus trapped in each Sarracenia leaf pitcher was profiled using 16S rRNA amplicon sequencing. We identified a surprising amount of bacterial diversity within each pitcher, but we also discovered bacteria whose abundance was specifically enriched in one of the two Sarracenia species. These differences in bacterial community representation suggest some biotic influence of the Sarracenia plant on the bacterial composition of their pitchers. Overall, our results suggest that bacterial selection due to factors other than geographic location, weather, or prey availability is occurring within the pitchers of these two closely related plant species. This indicates that specific characteristics of S. minor and S. flava may play a role in fostering distinct bacterial communities. These confined, naturally occurring microbial ecosystems within Sarracenia pitchers may provide model systems to answer important questions about the drivers of microbial community composition, succession, and response to environmental perturbations. IMPORTANCE This study uses amplicon sequencing to compare the bacterial communities of environmental samples from the detritus of the leaf cavities of Sarracenia minor and Sarracenia flava pitcher plants. We sampled the detritus at the same time and in the same geographic location, eliminating many environmental variables present in other comparative studies. This study revealed that different species of Sarracenia contain distinct bacterial members within their pitchers, suggesting that these communities are not randomly established based on environmental factors and the prey pool but are potentially enriched for by the plants' chemical or physical environment. This study of these naturally occurring, confined microbial ecosystems will help further establish carnivorous pitcher plants as a model system for answering important questions about the development and succession of microbial communities.
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10.1128/Spectrum.00696-21
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pubmed_460_17632
|
Chronic hemodialysis sessions, as developed in Seattle in the 1960s, were long procedures with minimal intra- and interdialytic symptoms. Over the next three decades, financial and logistical pressures related to the overwhelming number of patients requiring hemodialysis created an incentive to shorten dialysis time to four, three, and even two hours per session in a thrice weekly schedule. This method spread rapidly, particularly in the United States, after the National Cooperative Dialysis Study suggested that time of dialysis is of minor importance as long as urea clearance multiplied by dialysis time and scaled to total body water (Kt/Vurea) equals 0.95-1.0. This number was later increased to 1.3, but the assumption that hemodialysis time is of minimal importance, as long as it is compensated by increased urea clearance, remained unchanged. Patients accepted short dialysis as a godsend, believing that it would not be detrimental to their well being and longevity. However, Kt/Vurea measures only removal of low molecular weight substances and does not consider removal of larger molecules. Nor does it correlate with the other important function of hemodialysis, namely ultrafiltration. Whereas patients with substantial residual renal function may tolerate short dialysis sessions, patients with little or no urine output tolerate short dialyses poorly because at a given interdialytic weight gain the ultrafiltration rate is inversely proportional to dialysis time. Rapid ultrafiltration is associated with cramps, nausea, vomiting, headache, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control leading to left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality. Short, high-efficiency dialysis requires high blood flow, which increases demands on blood access. The classic, wrist arteriovenous fistula, the access with the best longevity and lowest complication rates, provides "insufficient" blood flow and is replaced with an arteriovenous graft fistula or an intravenous catheter. Moreover, to achieve high blood flows, large diameter intravenous catheters are used; these fit veins "too tightly" and so predispose to central-vein thrombosis. Longer hemodialysis sessions (5-8 hours, thrice weekly), as practiced in some centers, are associated with lower complication rates and better outcomes. Frequent dialyses (four or more sessions per week) with total weekly dialysis time sufficient to allow gentle ultrafiltration rates provide the best clinical results, but are associated with increased costs which are not properly reimbursed in the USA at present. Therefore, it is my strong belief that before a more appropriate reimbursement is available, a wide acceptance of longer, gentler dialysis sessions, in the current thrice weekly schedule, would improve overall hemodialysis results, decrease access complications, hospitalizations and mortality, particularly in anuric patients. Kt/Vurea should be abandoned as a measure of dialysis quality. The formula suggests that it is possible to decrease t as long as K is proportionately increased, but this is not true. The use of rigid, quantitative guidelines (e.g., spKt/Vurea of 1.3 per dialysis) assumes that all patients behave identically in response to therapeutic maneuvers, like the mean of the group, but this is also not true. The individual, clinical approach assumes that there are differences among patients, which require adjustment of dialysis schedule for each patient.
|
10.1177/039139880402700603
|
pubmed_864_531
|
OBJECTIVES
The objective of this article is to explore diagnostic decision making around psychological symptoms presenting to general practitioners (GPs) and psychiatrists, identify attitudinal and personality factors of possible relevance in these decisions, and compare GPs and psychiatrists to help identify potential educational targets.
METHODS
GPs and psychiatrists attended separate peer-facilitated workshops in which two case presentations were discussed. Decision making was explored by structured questions embedded in the workshop, with responses recorded by electronic keypad technology. Participants completed demographic questionnaires and measures of personality and attitudes to depression.
RESULTS
GPs and psychiatrists accorded emphasis to different elements of the history, and assigned different diagnoses based on the same set of symptoms. Both groups relied on non-pharmacological management for milder psychological symptoms; GPs were less likely to make a diagnosis of bipolar disorder. Traits of Extraversion and Agreeableness were associated with greater ease in treating depression.
CONCLUSIONS
Differences in diagnostic decision making likely reflect the different contexts of specialist and generalist practice. Educational targets may include information about key symptoms to assist in diagnostic precision, but further information is needed to determine the best match between diagnostic processes, context and outcome. An awareness of the role of personality factors may help when designing education and support programs.
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10.1177/1039856213486210
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pubmed_764_6002
|
Infiltration of activated CD4+ T cells and apoptosis of endothelial cells are present in the synovium of rheumatoid arthritis (RA). Using staphylococcal enterotoxin B (SEB) as an antigen, we examined the possible role of antigen (Ag)-dependent activation of CD4+ T cells by endothelial cells, in inducing endothelial cell apoptosis. The human endothelial cell line, EA.hy926 cells, was cultured with or without interferon-gamma (IFN-gamma) and further incubated with CD4+ T cells in the presence or absence of SEB. After this cocultivation, the cytotoxicity and Fas ligand (FasL) expression of CD4+ T cells were examined. A small percentage of EA.hy926 cells expressed HLA-DR and -DQ, and this expression was significantly augmented after IFN-gamma stimulation. Anti-Fas IgM-induced apoptosis was exhibited by both unstimulated and IFN-gamma-stimulated EA.hy926 cells. Cytotoxicity of CD4+ T cells toward SEB-pulsed unstimulated EA.hy926 cells was detected. Furthermore, when CD4+ T cells were incubated with IFN-gamma-stimulated, SEB-pulsed EA.hy926 cells with augmented HLA-DR and -DQ expression, this cytotoxicity was more significant. The addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas-Fc) reduced the cytotoxicity. FasL expression was induced in CD4+ T cells cocultured with SEB-pulsed EA.hy926 cells, especially when the EA.hy926 cells were IFN-gamma-stimulated. Furthermore, the addition of mAbs against CD54 and CD58 inhibited both the cytotoxicity and FasL expression of CD4+ T cells induced by SEB-pulsed EA.hy926 cells, indicating the importance of costimulatory molecules on EA.hy926 cells in activating CD4+ T cells. Our results suggest that CD4+ T cells are activated by endothelial cells in an Ag-dependent manner and subsequently express FasL, which induces Fas-mediated apoptosis of endothelial cells. This phenomenon may counteract the growth of RA synovium by inhibiting the proliferation of endothelial cells.
|
10.1006/bbrc.1997.7535
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pubmed_667_18345
|
The dendritic distribution of mitral/tufted (M/T) cells in the opossum accessory olfactory bulb (AOB) was investigated using intracellular injection of Lucifer yellow and DiI labeling. Lucifer yellow labeling demonstrated that the primary dendrites of M/T cells are restricted to one of the two subregions (anterior or posterior) of the glomerular layer. When DiI was placed in the anterior or posterior subregion of the glomerular layer, virtually all of the labeled cell bodies in the AOB were located in the anterior or posterior part of the M/T cell layer, respectively. These results demonstrate that the anterior and posterior subregions of the AOB glomerular layer are termination sites for dendrites belonging to distinct populations of M/T cells.
|
10.1097/00001756-199705260-00019
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pubmed_724_17641
|
Idiosyncratic hepatotoxicity is a well-known complication associated with aromatic antiepileptic drugs (AAED), and it has been suggested to occur due to the accumulation of toxic arene oxide metabolites. Although there is clear evidence of the participation of an immune process, a direct toxic effect involving mitochondria dysfunction is also possible. The effects of AAED on mitochondrial function have not been studied yet. Therefore, we investigated, in vitro, the cytotoxic mechanism of carbamazepine (CB), phenytoin (PT) and phenobarbital (PB), unaltered and bioactivated, in the hepatic mitochondrial function. The murine hepatic microsomal system was used to produce the anticonvulsant metabolites. All the bioactivated drugs (CB-B, PB-B, PT-B) affected mitochondrial function causing decrease in state three respiration, RCR, ATP synthesis and membrane potential, increase in state four respiration as well as impairment of Ca2+ uptake/release and inhibition of calcium-induced swelling. As an unaltered drug, only PB, was able to affect mitochondrial respiration (except state four respiration) ATP synthesis and membrane potential; however, Ca2+ uptake/release as well as swelling induction were not affected. The potential to induce mitochondrial dysfunction was PT-B>PB-B>CB-B>PB. Results suggest the involvement of mitochondrial toxicity in the pathogenesis of AAED-induced hepatotoxicity.
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10.1016/j.tiv.2008.03.004
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pubmed_576_18742
|
OBJECTIVES
Preeclampsia is the pregnancy specific disorder in which reduced organ perfusion and ischemia of the kidney, liver and brain can be detected. In the kidney, the most typical anatomopathological lesion is glomerular endotheliosis but renal tubular damage was also demonstrated. The NAG is an enzyme which is released into urine from the lysosomes of the proximal renal tubules epithelium and therefore increased urinary NAG activity is a marker of tubular damage or dysfunction.
DESIGN
The aim of the study was to assess the renal tubular damage in women with preeclampsia by measuring of urinary NAG activity.
MATERIALS AND METHODS
The study group consisted of 46 pregnant women in third trimester with preeclampsia. 36 normal pregnant women in third trimester and 26 healthy nonpregnant women served as two control groups. Urinary activity of NAG was measured in the second morning urine sample by colorimetric method and the results were expressed as NAG/creatinine ratio (U/mmol).
RESULTS
Urinary NAG/creatinine ratio was increased in normal pregnant women in third trimester (0.77 +/- 0.44 U/mmol) exceeding that of nonpregnant women (0.23 +/- 0.16). In women with preeclampsia, the urinary NAG/creatinine ratio was significantly higher when compared to the normal pregnant women in third trimester (1.46 +/- 1.63 U/mmol). There were no correlation between urinary NAG excretion and blood pressure results in women with preeclampsia.
CONCLUSIONS
The increased urinary NAG activity in women with preeclampsia seems to be a sign of proximal tubular damage. The renal function follow up study in such women is indicated.
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pubmed_576_18742
|
pubmed_973_22545
|
A 61-year-old Caucasian was admitted to Department of Chest Diseases and Tuberculosis, Medical University of Bialystok, Poland for progressive muscle weakness and weight loss. Eighteen months prior to admission, the patient had been diagnosed with pulmonary embolism. At that point he was started on Enoxaparin QD. Past medical history was unremarkable. In the interim, the patient developed fever, myalgia and progressive dyspnea. Physical examination on admission revealed a rash on his upper torso and back, and the extensor surfaces of all four extremities. Laboratory values included CPK 8229, MB fraction 219, LDH 981. Chest X-ray and CT scan revealed bilateral patchy consolidations and ground-glass opacities. EMG was consistent with myositis. The patient was started on solumedrol 40 mg i.v., b.i.d., and then switched to prednisone 40 mg b.i.d. His symptoms and muscle strength improved remarkably. The patient was discharged with prednisone with an outpatient follow up.
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10.1186/2047-783x-14-s4-162
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pubmed_1100_2515
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A total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del, XbaI, and EcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09; X+, 0.1; and R-, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy-Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between the ins/del and XbaI site polymorphisms of apo B (chi 2(4)) = 25.3; P < 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except for XbaI, which appeared to be associated with serum TG (as the log transform: R2 = 8.3; F = 4.8; P < 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F = 5.4; P < 0.01).
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10.1002/gepi.1370110103
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pubmed_125_8642
|
Chlamydia trachomatis serovar L2 and Chlamydia muridarum, which do not express FtsZ, undergo polarized cell division. During division, peptidoglycan assembles at the pole of dividing Chlamydia trachomatis cells where daughter cell formation occurs, and peptidoglycan regulates at least two distinct steps in the polarized division of Chlamydia trachomatis and Chlamydia muridarum. Cells treated with inhibitors that prevent peptidoglycan synthesis or peptidoglycan crosslinking by penicillin-binding protein 2 (PBP2) are unable to initiate polarized division, while cells treated with inhibitors that prevent peptidoglycan crosslinking by penicillin-binding protein 3 (PBP3/FtsI) initiate polarized division, but the process arrests at an early stage of daughter cell growth. Consistent with their distinct roles in polarized division, peptidoglycan organization is different in cells treated with PBP2 and PBP3-specific inhibitors. Our analyses indicate that the sequential action of PBP2 and PBP3 drives changes in peptidoglycan organization that are essential for the polarized division of these obligate intracellular bacteria. Furthermore, the roles we have characterized for PBP2 and PBP3 in regulating specific steps in chlamydial cell division have not been described in other bacteria.
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10.1038/s41598-020-69397-x
|
pubmed_624_19488
|
The effect of the merD gene on the expression of the mer operon was determined from the rates of accumulation of merA-lacZ fusion protein in the presence and absence of an active merD gene in trans. In the presence of the merD gene, beta-galactosidase activity was 2- to 4-fold lower. The merD gene was cloned in a T7 promoter expression vector and the MerD protein product was visualized by autoradiography.
|
10.1007/BF00260858
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pubmed_1055_4899
|
The collection of tears for chemical composition analysis is complicated by both the difficulty in sampling the tear film and the relatively low microliter volumes available for analysis. The experiments in this study are focused on the demonstration of a method for determining amino acids from tear samples. Phenol red thread was used to absorptively collect tear fluid for qualitative and quantitative analyses of amino acids in basal, reflex, and emotional tears. The thread is also used as a support for sample preparation followed by elution with a buffer. The phenol red indicator on the thread turns from yellow to red with 15-s tear absorption and allows accurate volume measurement from 100 nL to over 1 μL. Derivatization of amino acids was performed directly on the thread with primary amine reactive fluorescamine for fluorescence detection. Analyte elution was performed via centrifugation with the thread in a pipet tip suspended in a centrifuge tube. Collected tear eluate was analyzed via capillary electrophoresis with LED-induced fluorescence. Glycine, glutamate, and aspartate were baseline resolved and used for method characterization. Recoveries were at 50 % for a single derivation and elution step but average recoveries near 90 % were found with two-step processing. Glutamate and aspartate are shown to be stable stored on thread for 3 days. Basal, reflex, and emotional tears were analyzed from three subjects showing distinct amino acid profiles for each tear type. The demonstration of this method may facilitate the development of routine tear compositional analysis to assess ocular health. Graphical Abstract Schematic drawing of thread-based tear collection and quantitative analysis.
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10.1007/s00216-016-9624-7
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pubmed_465_12098
|
Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.
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10.1136/bmj.287.6396.863
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pubmed_40_20084
|
A putative prenyltransferase gene, NFIA_043650, was amplified from Neosartorya fischeri NRRL 181 and cloned into the expression vector pQE60. The deduced polypeptide consisting of 445 amino acids with a molecular mass of 51 kDa was overproduced in Escherichia coli and purified as His6-tagged protein to near homogeneity. The purified soluble protein was subsequently assayed with potential aromatic substrates in the presence of dimethylallyl diphosphate. HPLC analysis of the reaction mixtures revealed acceptance of all tested tryptophan-containing cyclic dipeptides. Isolation and structural elucidation of enzyme products of five selected substrates indicated a reverse C2-prenylation on the indole nucleus, proving the enzyme to be a cyclic dipeptide C2-prenyltransferase (CdpC2PT). Differing significantly from two known brevianamide F reverse C2-prenyltransferases NotF and BrePT which use cyclo-l-Trp-l-Pro as their preferred substrate, CdpC2PT showed a clear substrate preference for (S)-benzodiazepinedinone and cyclo-l-Trp-l-Trp with KM values of 84.1 and 165.2 µM and turnover numbers at 0.63 and 0.30 s(-1), respectively. A possible role of CdpC2PT in the biosynthesis of fellutanines is discussed.
|
10.1099/mic.0.069542-0
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pubmed_553_2467
|
Two cases of long-standing alopecia totalis treated with topical minoxidil are described. The mechanism of minoxidil hypertrichosis is discussed.
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10.1177/014107688207501208
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pubmed_27_2945
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Sustained release biodegradable microcapsules of AZT were prepared using different concentrations of copolymer of poly(lactic/glycolic) acid (PLGA 50:50 and PLGA 90:10). Solid microcapsules were collected following the complete evaporation of the solvent. The yield of microcapsules was increased two fold with a two-fold increase of the polymer concentration. The efficiency of encapsulation of AZT was also increased with the increase of the polymer concentration. These microcapsules were characterized using scanning electron microscopy. The dissolution of AZT from the microcapsules of PLGA (50: 50) was higher than the microcapsules of PLGA (90:10); the PLGA (50:50) microcapsules containing 1:10 drug/polymer ratio showed higher dissolution than the microcapsules containing 1:20 drug/polymer ratio. The PLGA (90:10) microcapsules containing 1:6 drug/polymer ratio showed higher dissolution than the microcapsules containing 1:10 drug/polymer ratio. In conclusion, the dissolution of AZT was dependent on the type of the copolymer used and the relative concentrations of the drug and the copolymer.
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10.3109/02652049609026014
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pubmed_701_14832
|
BACKGROUND
Sclerosing peritonitis (SP) is a serious complication of chronic ambulatory peritoneal dialysis (CAPD) that is characterized by thickened peritoneal membranes, leading to impaired ultrafiltration and intestinal obstruction. The aim of this study was to analyze the radiographic signs of SP in symptomatic patients and to compare them with the histological severity of the disease.
METHODS
In 14 patients with symptoms of intestinal obstruction related to SP, plain films of the abdomen, upper GI follow-through examinations, ultrasonography, and computed tomography were evaluated retrospectively. Imaging findings such as bowel motility, bowel wall and peritoneal thickness, and the presence of intraperitoneal fluid collections were correlated to the histological degree of the fibrosis.
RESULTS
Signs of intestinal obstruction and disturbed motility were present in all cases. In addition, patients with histologically severe SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications, and thickened peritoneal membranes, and suffered more often from postoperative complications.
CONCLUSION
The detection of characteristic radiographic signs in CAPD patients presenting with symptoms of intestinal obstruction may suggest the presence of severe SP and should lead to cautious surgical interventions.
|
10.1007/BF01213261
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pubmed_348_1584
|
In this paper, a detailed theoretical model is developed for studying the capillary filling dynamics of a non-Newtonian power-law obeying fluid in a microchannel subject to electrokinetic effects. Special attention is devoted to model the effects of the electroosmotic influences in the capillary advancement process, variable resistive forces acting over different flow regimes, and the dynamically evolving contact line forces, in mathematically closed forms. As an illustrative case study, in which the flow parameters are modeled as functions of the hematocrit fraction in the sample, the capillary dynamics of a blood sample are analyzed. Flow characteristics depicting advancement of the fluid within the microfluidic channel turn out to be typically non-linear, as per the relative instantaneous strengths of the capillary forces, electroosmotic forces and viscous resistances. Non-trivial implications of the blood hematocrit level and the imposed electric field on the progression of the capillary front are highlighted, which are expected to be of significant consequence towards the dynamics of electroosmotically aided capillary filling processes of biofluidic samples.
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10.1016/j.aca.2007.10.049
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pubmed_1061_24211
|
BACKGROUND
Bisphenol A (BPA), an estrogen-like endocrine disruptor used in plastics, has been associated with development and promotion of breast cancer, so plastic manufacturers shifted towards less-studied analogs, BPF and BPS. Studying the associated DNA methylome-wide mechanisms of these derivatives is timely, particularly in comparison with BPA.
METHODS
We assessed proliferation, cell cycle, and migration of breast cancer cells (estrogen receptor (ER)-positive: MCF-7 and ER-negative: MDA-MB-231) treated with BPF and BPS ± estrogen receptor inhibitor (ERI) in comparison to BPA ± ERI. RNA expression and activity of DNA (de)methylation enzymes and LINE-1 methylation were quantified. DNA methylome-wide analysis was evaluated in bisphenol-exposed cells and compared to clinical breast cancer data.
RESULTS
The three bisphenols caused ER-dependent increased proliferation and migration of MCF-7 but not MDA-MB-231 cells, with BPS being 10 times less potent than BPA and BPF. Although they have similar chemical structures, the three bisphenols induced differential DNA methylation alterations at several genomic clusters of or single CpG sites, with the majority of these being ER-dependent. At equipotent doses, BPA had the strongest effect on the methylome, followed by BPS then BPF. No pathways were enriched for BPF while BPA- and BPS-induced methylome alterations were enriched in focal adhesion, cGMP-PKG, and cancer pathways, which were also dysregulated in methylome-wide alterations comparing ER-positive breast cancer samples to adjacent normal tissues.
CONCLUSIONS
The three bisphenols have important epigenetic effects in breast cell lines, with those of BPA and BPS overlapping with cancer-related pathways in clinical breast cancer models. Hence, further investigation of their safety is warranted.
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10.1186/s13148-019-0725-y
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pubmed_58_22688
|
Large perpendicular magnetic anisotropy (PMA) in transition metal thin films provides a pathway for enabling the intriguing physics of nanomagnetism and developing broad spintronics applications. After decades of searches for promising materials, the energy scale of PMA of transition metal thin films, unfortunately, remains only about 1 meV. This limitation has become a major bottleneck in the development of ultradense storage and memory devices. We discovered unprecedented PMA in Fe thin-film growth on the [Formula: see text] N-terminated surface of III-V nitrides from first-principles calculations. PMA ranges from 24.1 meV/u.c. in Fe/BN to 53.7 meV/u.c. in Fe/InN. Symmetry-protected degeneracy between x2 - y2 and xy orbitals and its lift by the spin-orbit coupling play a dominant role. As a consequence, PMA in Fe/III-V nitride thin films is dominated by first-order perturbation of the spin-orbit coupling, instead of second-order in conventional transition metal/oxide thin films. This game-changing scenario would also open a new field of magnetism on transition metal/nitride interfaces.
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10.1126/sciadv.aar7814
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pubmed_673_9261
|
Cell lines were established from three hamster melanomas. One was a spontaneous melanotic tumour which lost its ability to produce pigment. Two were induced with DMBA (9.10 dimethyl 1,2-benz/a/anthracene). One of these was pigmented. The two amelanotic lines (CHT-1 and 2) produced highly malignant amelanotic tumours after reimplantation of tissue culture cells. Electron microscopy showed that melanin forming organelles were absent. Tyrosinase activity was also absent. The line established from the pigmented tumour (CHT-8) retained its pigment production for the first seven transfers. Cells from these cultures produced slow growing pigmented tumours. Cells from the 7th to the 35th transfer, a period of 28 weeks, failed to produce tumours but cells from the 36th and subsequent transfers produced slow growing amelanotic tumours. The change in tumorigenicity was not related to changes in the growth rate of the cells in vitro: this remained constant after the 11th transfer generation. Tyrosinase activity and a whole range of melanin forming organelles were present in cells of transfers 1 to 7 but absent from subsequent transfers. Type A and H virus particles were present in the two amelanotic cell lines, CHT-1 and 2. Although the two amelanotic lines produced highly malignant tumours the loss of a differentiated character--melanin production--was not invariably associated with increased malignancy. Three cell lines should provide a good system for studying the relationship between tumour differentiation and growth.
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pubmed_673_9261
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pubmed_489_21945
|
Arterial stiffness is an important risk factor of impaired left ventricular (LV) diastolic function as well as systolic dysfunction. The cardio-ankle vascular index (CAVI) and the ambulatory arterial stiffness index (AASI) can evaluate arteriosclerosis. We analyzed the relationship between arterial stiffness and diastolic function, and then compared the two methodologies to assess which method could serve as a more informative tool for diastology. In total, 136 patients with hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and echocardiography including ventricular arterial coupling (VAC). Arterial stiffness was estimated using both CAVI and AASI derived from ABPM. Patients were classified into LV diastolic dysfunction and normal function groups. Those with diastolic dysfunction had a higher CAVI and AASI. Aside from LV torsion, mitral inflow parameters, tissue Doppler velocities and VAC showed a significantly greater association with CAVI, relative to AASI. The receiver operating characteristic curve analysis revealed that CAVI [area under the curve (AUC) = 0.869, p < 0.001] provided significantly more favorable accuracy for diastolic dysfunction compared with AASI (AUC = 0.672, p = 0.004). Multiple logistic regression analyses showed that CAVI [Odds ratio (OR) = 5.1, p = 0.009] had a greater association with diastolic dysfunction, relative to age, systolic blood pressure or AASI (OR = 1.4, p = 0.043). This study indicates that CAVI clinically provides diastolic functional information much better in hypertensive patients than AASI.
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10.3109/10641963.2013.804544
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pubmed_1085_2140
|
A telemedical pilot-project involving two rural primary health care centers in Tärnaby/Storuman in Southern Lappland and the University Hospital of Umeå was carried out during the period Sept. 1, 1996-Dec. 31, 1998. Out of 169 consultations in all, 40 pertained to dermatology, 50 to ENT, 40 to orthopedics, and a further 27 to other specialties (surgery, medicine and gynecology). Among the 169, 47 cases were successfully managed via telemedicine. 30% of consultations were made in order to secure a second opinion. The remaining 70% were made in order to seek advice concerning a possible referral. At the telemedical visit, patients indicated a satisfaction score of 5.5 on a scale up to 6.0. The GP's rated the educational value at 4.4. After completion of the pilot-project, a survey of acceptance and ratings of the future potential of telemedicine for the health care system was carried out among 191 doctors and other health care workers in Västerbotten county. Using a similar graded scale up to 6.0, physicians rated telemedicine as regards utility for patients and quality of care at 4.6 and 4.5 respectively, somewhat higher than they rated the consequences of telemedical consulting for their working conditions and health care organizations, at 3.8 and 4.1 respectively. Despite a low volume of patients in the pilot project, we can conclude that telemedical consultations seem to reduce the number of referrals and raise the level of competency of the GP's. It's important to find further fields of application, as well as further ways of working and organizing the communication network in order to increase volume.
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pubmed_1085_2140
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pubmed_313_5776
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Conformist social learning can have a pronounced impact on the cultural evolution of human societies, and it can shape both the genetic and cultural evolution of human social behavior more broadly. Conformist social learning is beneficial when the social learner and the demonstrators from whom she learns are similar in the sense that the same behavior is optimal for both. Otherwise, the social learner's optimum is likely to be rare among demonstrators, and conformity is costly. The trade-off between these two situations has figured prominently in the longstanding debate about the evolution of conformity, but the importance of the trade-off can depend critically on the flexibility of one's social learning strategy. We developed a gene-culture coevolutionary model that allows cognition to encode and process information about the similarity between naive learners and experienced demonstrators. Facultative social learning strategies that condition on perceived similarity evolve under certain circumstances. When this happens, facultative adjustments are often asymmetric. Asymmetric adjustments mean that the tendency to follow the majority when learners perceive demonstrators as similar is stronger than the tendency to follow the minority when learners perceive demonstrators as different. In an associated incentivized experiment, we found that social learners adjusted how they used social information based on perceived similarity, but adjustments were symmetric. The symmetry of adjustments completely eliminated the commonly assumed trade-off between cases in which learners and demonstrators share an optimum versus cases in which they do not. In a second experiment that maximized the potential for social learners to follow their preferred strategies, a few social learners exhibited an inclination to follow the majority. Most, however, did not respond systematically to social information. Additionally, in the complete absence of information about their similarity to demonstrators, social learners were unwilling to make assumptions about whether they shared an optimum with demonstrators. Instead, social learners simply ignored social information even though this was the only information available. Our results suggest that social cognition equips people to use conformity in a discriminating fashion that moderates the evolutionary trade-offs that would occur if conformist social learning was rigidly applied.
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10.1371/journal.pone.0168551
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pubmed_857_18851
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Soluble, single-chain molecules for two MHC class I alleles, H-2Kd and H-2Kb, were used to analyze the kinetics of antigenic peptide binding to MHC. After MHC preloading with radiolabeled or fluorescent peptides, the observed rate of MHC-peptide complex dissociation increased after addition of an excess of unlabeled competitor peptide. Although exogenous peptides conforming to the allele-specific motif were required for the enhanced complex dissociation to occur, the dissociation rate of the complex was independent of exogenous peptide concentration. Similarly, the association rate of exogenous peptides was independent of concentration, reflecting the presence of low affinity peptides in the binding sites of the recombinant MHC proteins; the sequences of these endogenous peptides conform to the consensus motif for the MHC allele studied. Finally, the association rate of exogenous peptide decreased when MHC molecules were preloaded with high affinity peptides, and the binding of labeled high affinity peptide to isolated recombinant MHC was faster than the subsequent dissociation observed in the presence of competitor peptide. Taken together, these results imply that the rate of exogenous peptide binding is limited by the dissociation rate of the previously bound peptides.
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pubmed_857_18851
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pubmed_789_8551
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BACKGROUND
Early diagnosis of critical congenital heart defects (CCHD) may be missed both during prenatal echocardiography and the short stay in the neonatal nursery, leading to circulatory collapse or death of the newborn before readmission to hospital.
AIM
To assess the usefulness of pulse oximetry as a screening test in early diagnosis of CCHD in newborns.
METHODS
A prospective screening pulse oximetry test was conducted in 51 neonatal units in the Mazovia province of Poland as part of the POLKARD 2006-2008 programme between 16 January, 2007 and 31 January, 2008. Newborns with no circulatory symptoms or coexisting diseases, and no prenatal diagnosis, were enrolled. The test was performed between the 2(nd) and 24(th) hours of life in stable newborns. A double arterial oxygen saturation (SpO(2)) reading < 95% on a lower extremity led to cardiovascular evaluation and echocardiography.
RESULTS
From a population of 52,993 newborns (14.2% of births in Poland), a group of 51,698 asymptomatic infants was isolated. CCHD was diagnosed solely by pulse oximetry in 15 newborns, which constituted 18.3% of all CCHD; 14 (0.026%) false positives were obtained and there were four false negative results. The sensitivity of the test was 78.9% and specificity 99.9%. The positive predictive value was 51.7% and negative 99.9%.
CONCLUSIONS
Pulse oximetry fulfilling the screening test criteria, performed on a large population of newborns in Poland, proved useful in supporting prenatal diagnostics and postnatal physical examination in the early detection of initially asymptomatic CCHD. Good sensitivity and specificity results of the pulse oximetry test have allowed it to be recommended for use in neonatal units nationwide.
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pubmed_789_8551
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pubmed_1069_1033
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By using the techniques of in situ hybridization histochemistry and immunocytochemistry, we have found that both glial fibrillary acidic protein messenger RNA levels and glial fibrillary acidic protein immunoreactive surface density in the arcuate nucleus and median eminence are modulated by both the neonatal and adult sex steroid environments. No effect was seen on the number of immunoreactive glia. Intact adult males had significantly higher glial fibrillary acidic protein messenger RNA levels and glial fibrillary acidic protein immunoreactive surface density than females. Both adult and neonatal castration of male animals significantly reduced glial fibrillary acidic protein messenger RNA levels and glial fibrillary acidic protein immunoreactive surface density. Neonatal and adult testosterone treatment increased both of these parameters in both sexes; however, there was no additive effect of the steroid treatments. Glial cells are involved in the proliferation, survival, migration and maturation of neurons, as well as in the modulation of synaptic connectivity, and therefore it follows that hormonal modulation of glia may mediate some of the known steroid effects on neurons. The data reported here show that astroglia are significantly influenced by both the neonatal and adult sex steroid environments and suggest that some of the steroid effects on neurons during both of these developmental periods may be mediated, at least in part, through modulation of glial cells.
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10.1016/0306-4522(95)00250-m
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pubmed_483_25051
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Reading is a complex cognitive ability, which relies on visual and language processing as well as on executive functions (EFs). Recent studies have demonstrated that increased reading ability in children aged 7-17 years is related to greater activation of cognitive control regions during verb generation, a task which merges linguistic and cognitive control ability. The aim of the current study is to determine the relationships between neural circuits specifically related to EF and reading ability. We focused on functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a region involved in EF and is part of the frontoparietal network during a verb generation task, and reading ability in seventeen 8-12-year-old typical readers. Results show positive functional connectivity between the left and right DLPFCs and regions related to cognitive control and visual processing while generating verbs. Increased reading ability was positively correlated with greater functional connectivity between the left and right DLPFCs and right-lateralized visual processing regions. The current study highlights the importance of neural circuits related to EF during both verb generation and reading and points to the role of the right occipital cortex in generating verbs as well as automatic word recognition in typical readers.
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10.1089/brain.2018.0655
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pubmed_547_15576
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Cases of human hantavirus disease have been reported in Chile since 1995, most of them in people living in rural and periurban areas. We conducted a peridomestic study of small mammals to evaluate the relationships between the presence of rodents with antibodies to Andes virus confirmed human cases of hantavirus pulmonary syndrome in southcentral Chile. The results of 20 sampled sites, which involved the capture of 272 mice over an 18-month period, showed the occurrence of 10 small mammal species, of which Oligoryzomys longicaudatus was the only seropositive species for hantavirus, with an intra-specific serologic rate of 10.4%.
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pubmed_547_15576
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pubmed_888_8565
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Combinatorial chemistry can be efficiently used for the synthesis and evaluation of binding properties of libraries of synthetic receptors. This approach has been applied particularly to 'tweezer' and other 'multi-armed' receptors, and has been used for the identification of receptors for peptides in aqueous media, and for the development of new sensors and sensor arrays.
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10.1016/j.cbpa.2004.04.014
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pubmed_400_220
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Because respiratory viruses play an important role in the causation and pathogenesis of acute otitis media (AOM), determining which virus has infected a child is important with respect to vaccines and antiviral drugs. In some instances, this information might be used to prevent the occurrence of AOM. We used a rapid, economical, and sensitive diagnostic system involving a multiplex nested reverse transcription-polymerase chain reaction (RT-PCR) assay to detect various respiratory viruses in clinical specimens of middle ear fluid (MEF) from children with AOM in our hospital. Multiplex RT-PCR was completed on 40 MEF samples from 28 infants and children less than 6 years old with AOM. Viral RNA was detected in 17 MEF samples (43%). Respiratory syncytial virus type A was present in 12 samples, adenovirus in 3, rhinovirus in 2, and influenza A (H3N2) in 1. The multiplex RT-PCR assay is recommended to clinical laboratories that are considering adoption of a molecular technique for viral diagnosis.
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10.1177/000348940311200311
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pubmed_774_21708
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The majority of patients with newly diagnosed chronic myeloid leukemia (CML) will enjoy a life expectancy equivalent to that of unaffected individuals, but will remain on life-long treatment with a concomitant requirement for on-going hospital interactions for molecular monitoring and drug dispensing. In order to determine more accurately the frequency of monitoring required, we performed a 'real-life' retrospective single-center cohort study of 450 patients with CML in at least major molecular remission (MR3) to analyze the risk of loss of MR3 [defined as at least 2 consecutive real-time quantitative polymerase chain reaction (RT-qPCR) results >0.1% International Scale (IS)]. Patients who achieved sustained MR4 (sMR4, BCR-ABL1 RT-qPCR <0.01% IS for 12 months) had a probability of loss of MR3 at 1 and 5 years of 0 and 2.6% (95%CI: 1.2-5.4) respectively, compared to 4.4% (95%CI: 1.9-9.8) and 25.4% (95%CI: 16.7-36.7) respectively, in those who achieved sustained MR3 (sMR3) but not sMR4 (P<0.001). No patient who improved their response to a deep molecular level (at least MR4) lost MR3 if they were considered compliant, had no history of resistance and remained on standard dose tyrosine kinase inhibitor (TKI). MR4 maintained for at least one year represents a secure response threshold for patients with CML, after which no MR3 loss occurs if certain conditions are satisfied (standard TKI dose, full compliance, and lack of previous TKI resistance). This finding may justify reduction of the frequency of hospital interaction, with an associated positive impact on quality of life, survivorship, and economic burden to both patients and healthcare providers.
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10.3324/haematol.2018.214809
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pubmed_543_148
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The purpose of this study was to determine which echocardiographic views most reliably demonstrate the maximum velocity of a tricuspid regurgitant jet in the evaluation of pulmonary artery systolic pressure. Consecutive patients seen in three echocardiographic laboratories during a 3-month period were enrolled. A complete Doppler examination was performed on each patient, including a continuous-wave Doppler evaluation of tricuspid regurgitation in each of seven views. All seven views were used to determine the maximum velocity of tricuspid regurgitation. Of the 1163 studies, 866 (75%) had some tricuspid regurgitation by color-flow Doppler and 614 (53%) had a measurable velocity of tricuspid regurgitation in at least one view. No single echocardiographic view consistently yielded the maximum velocity of tricuspid regurgitation. The apical four-chamber view alone was inadequate. All seven views must be used to be certain that the maximum velocity of tricuspid regurgitation has been obtained.
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10.1016/s0894-7317(05)80358-x
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pubmed_194_8026
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CSNP dynamics was studied on 13 subjects in three experimental situations: 1) In combinations of acoustic and photic stimuli without performance of movements; 2) During the pressing of the palm at the moment of the anticipated photic stimulus; 3) After preliminary switching off of the photic stimulus. In the first situation CSNP does not appear; in the second, it has a maximum amplitude at the unitial stages of movement elaboration at a definite time interval, and in the third, CSNP amplitude does not decrease during 300 stimuli combinations. The CSNP amplitude, configuration and stability depend on the degree of complexity of the motor task. It has been assumed that CSNP reflects a non-specific activation of frontal and central parts of the human brain, against the background of which integration of sensory information takes place as well as the formation of a temporal program of the subsequent motor act.
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pubmed_194_8026
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pubmed_791_13053
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Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, methylate inorganic arsenic to mono-, di-, and trimethylated arsenic metabolites, which the organism can excrete. In humans and other eukaryotic organisms, the arsenite methyltransferase (AS3MT) protein methylates arsenite. AS3MT sequences from eukaryotic organisms group phylogenetically with predicted eubacterial AS3MT sequences, which has led to the suggestion that AS3MT was acquired from eubacteria by multiple events of horizontal gene transfer. In this study, we evaluated whether 55 (out of which 47 were predicted based on protein sequence similarity) sequences encoding putative AS3MT orthologues in 47 species from different kingdoms can indeed methylate arsenic. Fifty-three of the proteins showed arsenic methylating capacity. For example, the predicted AS3MT of the human gut bacterium Faecalibacterium prausnitzii methylated arsenic efficiently. We performed a kinetic analysis of 14 AS3MT proteins representing two phylogenetically distinct clades (Group 1 and 2) that each contain both eubacterial and eukaryotic sequences. We found that animal and bacterial AS3MTs in Group 1 rarely produce trimethylated arsenic, whereas Hydra vulgaris and the bacterium Rhodopseudomonas palustris in Group 2 produce trimethylated arsenic metabolites. These findings suggest that animals during evolution have acquired different arsenic methylating phenotypes from different bacteria. Further, it shows that humans carry two bacterial systems for arsenic methylation: one bacterium-derived AS3MT from Group 1 incorporated in the human genome and one from Group 2 in F. prausnitzii present in the gut microbiome.
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10.1021/acs.chemrestox.0c00375
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pubmed_796_4462
|
Equine encephalosis virus (EEV) is an orbivirus associated with a peracute illness of horses in southern Africa. The virus has now been partially purified for the first time and characterized on a molecular level. The virion is composed of 10 dsRNA segments and a protein capsid consisting of at least seven structural proteins that vary in Mr from 36,000 to 120,000. Partial clones of six of the dsRNA segments of EEV serotype Cascara were obtained and analysed for possible use as serotype-specific or group-specific probes in the detection of EEV dsRNA. Cloned fragments of genome segments 3, 8 and 10 were found to show high conservation of these segments, hybridizing to dsRNA from the six EEV serotypes under conditions that indicated more than 90% sequence homology. The genome segment 2-specific probe did not hybridize with dsRNA from any of the other EEV serotypes, suggesting that this segment encodes the serotype-specific antigen of EEV. Cross-hybridization of probes from genome segments 3 and 5 with dsRNA from bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and African horse sickness virus (AHSV) indicated that EEV is more closely related to BTV and EHDV than to AHSV. Both probes can be used to distinguish between EEV and AHSV dsRNA.
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10.1099/0022-1317-70-8-2007
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pubmed_34_3708
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The effects of prematuration (PM) of bovine oocytes with butyrolactone I (BLI) for 24h on meiosis progression, cell structures and embryo development were assessed. Germinal vesicle (GV) rates decreased (97.4-65.1%, P<0.05) with decreasing BLI concentrations (100-25microM). Without BSA in PM medium, GV rates were similar (98.7-97.2, P>0.05) with low BLI (10-25microM). After in vitro maturation (IVM) for 24h, metaphase II (MII) rates for controls (IVM only) were similar (91.1%, P>0.05) to PM with 10microM BLI in BSA-free medium (B10=91.5%) and 100microM BLI in medium with BSA (B100=92.4%). Meiosis resumption occurred earlier in treated oocytes (71.4-74.3% in GV for B10 and B100, respectively, after 6h IVM compared with 97.3% in controls, P<0.05). By 18h of IVM, most oocytes reached MII (72.0-78.9%, P>0.05). Microtubules and microfilaments were unaffected by BLI. Cortical granules (CG) migration was reversibly blocked by BLI. Mitochondria translocation was partially blocked by PM culture and after IVM more oocytes in B10 and B100 (95.2 and 98.2%, respectively) had mitochondria translocated to a mature pattern (all cytoplasm) than controls (81.5%, P<0.05). Cleavage rates were similar (81-87%, P>0.05), but blastocysts (day 7) decreased in B100 (33.0%, P<0.05) compared with controls and B10 (38.3 and 41.6%, respectively). Day 8 hatching rates (11.0-19.2%) and mean total cell numbers (136-150) were similar (P>0.05). PM did not improve oocyte competence but also did not cause major structural alterations, suggesting that PM may be improved and used to study the mechanisms involved in oocyte differentiation.
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10.1016/j.anireprosci.2007.07.002
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pubmed_825_6947
|
Overall, the studies available to date show that ketorolac is a powerful analgesic with no action on the central nervous system and a long-lasting effect of rapid onset. The analgesic effectiveness of ketorolac in the treatment of moderate to severe pain, is comparable with that of 10-12 mg of morphine, 100 mg of pethidine, or 30 mg of pentazocine. However, ketorolac, an inhibitor of prostaglandin synthesis, is not subject to the strict regulations of the narcotic drugs law. On account of its favorable adverse reactions profile, ketorolac is particularly well suited for the treatment of postoperative pain. Further major indications are pain associated with trauma to bones and muscles, as also cancer-related pain, in which area, a "saving effect" on simultaneously employed opiates and opioids can be achieved.
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pubmed_825_6947
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pubmed_300_9994
|
In our study of nursing home residents with clinically suspected urinary tract infection who did not require the use of an indwelling catheter, we identified bacteria isolated from urine samples, the resistance patterns of these isolated bacteria, and the antibiotic therapy prescribed to the residents. Escherichia coli, the predominant organism isolated, frequently was resistant to commonly prescribed oral antibiotics. Trimethoprim-sulfamethoxazole remains the best empiric antimicrobial therapy for a urinary tract infection, but nitrofurantoin should be considered if E. coli is identified.
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10.1086/647981
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pubmed_821_18856
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Synaesthesia is an unusual perceptual phenomenon in which events in one sensory modality induce vivid sensations in another. Individuals may 'taste' shapes, 'hear' colours, or 'feel' sounds. Synaesthesia was first described over a century ago, but little is known about its underlying causes or its effects on cognition. Most reports have been anecdotal or have focused on isolated unusual cases. Here we report an investigation of 15 individuals with colour-graphemic synaesthesia, each of whom experiences idiosyncratic but highly consistent colours for letters and digits. Using a colour-form interference paradigm, we show that induced synaesthetic experiences cannot be consciously suppressed even when detrimental to task performance. In contrast, if letters and digits are presented briefly and masked, so that they are processed but unavailable for overt report, the synaesthesia is eliminated. These results show that synaesthetic experiences can be prevented despite substantial processing of the sensory stimuli that otherwise trigger them. We conclude that automatic binding of colour and alphanumeric form in synaesthesia arises after initial processes of letter and digit recognition are complete.
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10.1038/35069062
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pubmed_638_16327
|
To assess the importance of only IgA antibody positivity in the peptide-based ELISA (P-ELISA) examination of kinetic behaviors of antibodies (IgA, IgG) to Chlamydia trachomatis, 426 sera from 52 follow-up antigen-positive patients were assayed. In part, a microimmunofluorescence (MIF) test and an immunoblot (IB) assay were also used for confirmation. The results showed that the positivity rates of IgA and IgG antibodies were 82.7 and 96.2%, respectively, at the first testing. One patient had both IgA- and IgG-negative antibodies at the first testing, but this became only IgA-positive and then IgG-positive. The patient was co-infected with Candida albicans and C. trachomatis, and saw a gynecologist for the symptom of itching. Although the major outer membrane protein was negative in IB assay, the results of the MIF test and absorption experiments were positive. MIF titers for IgA and IgG antibodies to C. pneumoniae were <1:8 and 1:32, respectively, at the peak level of P-ELISA. These findings seem to suggest that when only the IgA antibody is detected by P-ELISA, C. trachomatis infection may be present at an early stage, so confirmation via testing for C. trachomatis is needed.
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pubmed_638_16327
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pubmed_718_18252
|
Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab')2 fragment binding to NCI-H69 was 1.02 x 10(8)/M while that to the glioma cell line U87MG was 1.22 x 10(8)/M. Iodine-125-labeled GA-17 F(ab')2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87 +/- 1.34% g-1 (mean +/- SD, n = 5) 24 h after injection. On the other hand, control monoclonal F(ab')2 fragments accumulated in the xenografted tumor at 0.75 +/- 0.30% g-1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')2 was 0.60. In conclusion, the radiolabeled GA-17 F(ab')2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.
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10.1007/BF01236381
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pubmed_467_3221
|
Past health impact assessments of ambient fine particulate matter (particles with an aerodynamic diameter ≤2.5 μm; PM2.5) have generally considered mass concentration only, despite PM2.5 being a heterogeneous mixture. Given constant changes in the concentration and the composition of atmospheric aerosol, uncertainty exists as to whether the current focus on PM2.5 mass or individual components may fully characterize the health burden of PM2.5. We proposed a component-adjusted method that jointly estimates the health impacts of PM2.5 and its major components while allowing for a potential nonlinear PM2.5-outcome relationship. Using this method, we quantified the effects of PM2.5 on the risks of developing acute myocardial infarction (AMI) and dying from cardiovascular causes in comparison to three traditional approaches in the entire adult population across Ontario, Canada. We observed that PM2.5 was positively associated with AMI incidence and cardiovascular mortality with all four methods. Compared to the traditional approaches, however, the new component-adjusted approach demonstrated a significant improvement in explaining the health impacts of PM2.5, especially in the presence of a nonlinear PM2.5-outcome relationship. Using the new approach, we found that the effects of PM2.5 on AMI incidence and cardiovascular mortality may be 10% to 27% higher than what would be estimated from the conventional approaches examining PM2.5 alone.
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10.1021/acs.est.9b06861
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pubmed_598_8566
|
the non-edible fruit parts of Casimiroa edulis Llave et were evaluated for their active constituents and their potential as antioxidants, anti-inflammatory and antitumor activity. Fruits peel (FP) and seeds kernel (SK) of Casimiroa edulis Llave et Lex. were extracted successively with hexane and then methanol. Fatty acids were prepared from hexane extracts and identified by GC. Total flavonoid, phenolic acids and tannins contents in methanol extracts were determined by UV spectrophotometer and identified by HPLC. Antioxidant, in-vitro anti-inflammatory activity and antitumor effect against Caco-2 cell line were determined. GC analysis of hexane extracts showed that oleic acid (47.00%) was the major unsaturated fatty acids in both extracts while lignoceric acid (15.49%) is the most abundant saturated fatty acid in (FP). Total phenolic, flavonoid and tannin contents in (FP) & (SK) methanol extracts were; 37.5±1.5, 10.79±0.66 and 22.28±0.23 for (FP); 53.5±1.5mg/g, 14.44±0.32 mg/g; and 53.73±3.58 mg/g for (SK) respectively. HPLC analysis of methanol extract revealed that; the major phenolic compound was pyrogallol in (FP) and p-hydroxybenzoic acid in (SK), the major flavonoid was luteolin 6-arabinose-8-glucose in (FP) and acacetin in (SK). This study showed that non-edible parts of C. edulis fruit is a rich source of different phenolic compounds and fatty acids which has great antioxidant, anti-inflammatory and antitumor activities; that could be used as a natural source in pharmaceutical industry.
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10.15171/apb.2017.079
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pubmed_471_11042
|
Apoptotic cells expose Phosphatidylserine (PS), that serves as an "eat me" signal for engulfing cells. Previous studies have shown that PS also marks degenerating axonsduring developmental pruning or in response to insults (Wallerian degeneration), but the pathways that control PS exposure on degenerating axons are largely unknown. Here, we used a series of in vitro assays to systematically explore the regulation of PS exposure during axonal degeneration. Our results show that PS exposure is regulated by the upstream activators of axonal pruning and Wallerian degeneration. However, our investigation of signaling further downstream revealed divergence between axon degeneration and PS exposure. Importantly, elevation of the axonal energetic status hindered PS exposure, while inhibition of mitochondrial activity caused PS exposure, without degeneration. Overall, our results suggest that the levels of PS on the outer axonal membrane can be dissociated from the degeneration process and that the axonal energetic status plays a key role in the regulation of PS exposure.
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10.1038/s41419-018-1155-z
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pubmed_938_2090
|
Actual values for capillary hematocrits at 24 and 48 hours of life, through a hospital sample, representative of our population, were obtained; results were 58 +/- 7% (X +/- 1 DS) for both. These results were correlated to the initial hematocrit (50 +/- 5%), with had been reported in the first part of the series. The relationship between capillary hematocrits and the initial one, was very good, and between the capillary ones, was oven better. This relationship persisted after distributing the sample in four groups: Apgar, crying (if it presented before or after clamping) and the features of amniotic fluid. This demonstrates that capillary hematocrits, are as reliable as venous, central and peripheral hematocrit (in this case, from umbilical chord blood), contrary to what has been previously reported in literature. The presence of chord loop or circular, was analyzed also, when it was possible.
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pubmed_938_2090
|
pubmed_1042_5262
|
Continuous drug product manufacturing is slowly being implemented in the pharmaceutical industry. Although the benefits related to the quality and cost of continuous manufacturing are widely recognized, several challenges hampered the widespread introduction of continuous manufacturing of drug products. Current review presents an overview of state-of-the art research, equipment, process analytical technology implementations and advanced control strategies. Additionally, guidelines and regulatory viewpoints on implementation of continuous manufacturing in the pharmaceutical industry are discussed.
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10.1016/j.ijpharm.2020.119194
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pubmed_997_15473
|
Therapeutic options for locally advanced or metastatic squamous cell carcinoma were previously very limited and not standardized. With the approval of the monoclonal antibody cemiplimab, which targets the programmed death-1 receptor (PD-1), the prognosis of affected patients has improved significantly, and in some cases sustained complete remission can be achieved.This case report describes a multimorbid, 81-year-old patient who was initially treated with cemiplimab due to extensive squamous cell carcinoma frontoparietal with cranial dome infiltration and invasion intracranially. Immune-mediated side effects did not occur. With clinical and radiologic remission, in an interdisciplinary collaboration the residual finding was surgically resected, and the defective cranial dome was reconstructed. Histologically, pathological complete remission of squamous cell carcinoma was demonstrated. At 6 months postoperatively, there was no evidence of local recurrence or metastasis.This case exemplifies a patient who, despite his advanced age and co-morbidities, benefited from initiated immune checkpoint inhibitor therapy. Furthermore, it shows the relevance of an interdisciplinary/multimodal therapy regime in the management of this tumor entity, which is increasing in incidence.
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10.1055/a-1949-2936
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pubmed_64_18915
|
Repetitive nonsuicidal self-injury (R-NSSI) is an extreme manifestation of nonsuicidal self-injury (NSSI) behavior that causes bodily harm and emotional and personality disorders. It is a growing concern, especially among adolescents; therefore, this study aims to provide empirical support for effective interventions on R-NSSI behavior among adolescents in China. We used data of about 1180 students from a survey conducted in seven middle schools in Xi'an, China, and applied multiple logistic regression to analyze NSSI and R-NSSI among male and female students, including their influencing factors. We found no significant difference between male and female students' R-NSSI; however, regarding influencing factors, male students had more violent experiences and less social support than female students. Parental and familial factors played the most prominent role in social support. Social support was found to be a main-effect mechanism in the effect of violent experiences on R-NSSI among male students, whereas the mechanism had both a main effect and a certain buffer effect among female students. R-NSSI was found to be more prevalent among younger children, children with siblings, and those with romantic relationship experiences. We also found that healthy adolescent development involves the participation of families and schools. Health education should be conducted according to the students' sex and characteristics.
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10.3390/ijerph18073347
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pubmed_1129_6737
|
Objective The incidence of metabolic syndrome (MS) increases after liver transplantation. This study was performed to evaluate the impact of MS on patients' quality of life after liver transplantation. Methods We collected the medical records of 152 patients during their post-liver transplantation outpatient follow-up. Quality of life was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey. Data on the patients' general condition as well as MS-related indicators were assessed in all patients. Based on the MS diagnostic criteria proposed by the International Diabetes Federation in 2005, the patients were divided into two groups: those with and without MS. We then analyzed the factors influencing MS and their impact on the patients' quality of life. Results After liver transplantation, age and underlying liver disease were significantly associated with MS and diabetes, and sex and body mass index were associated with central obesity. Central obesity affected the patients' general health (GH) score and health transition (HT) score, and hypertension affected their GH score and physical component score (PCS). Conclusions After liver transplantation, central obesity had a negative impact on patients' GH score and HT score, and hypertension affected their GH score and PCS.
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10.1177/0300060518779513
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pubmed_534_9824
|
In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability, or injury (Australian Institute of Health and Welfare and Australasian Association of Cancer Registries, 2012). Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchidectomy and chemotherapy. Even then, prognosis is poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases which showed sustained and complete response to adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin.
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10.1155/2015/345018
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pubmed_308_5559
|
Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification.
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10.1016/j.bbrc.2016.01.044
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pubmed_297_5108
|
The microtubule-associated protein Tau plays a key role in the neuropathology of Alzheimer's disease by forming intracellular neurofibrillary tangles. Tau in the normal physiological condition helps stabilize microtubules and transport. Tau aggregates due to various gene mutations, intracellular insults and abnormal post-translational modifications, phosphorylation being the most important one. Other modifications which alter the function of Tau protein are glycation, nitration, acetylation, methylation, oxidation, etc. In addition to forming intracellular aggregates, Tau pathology might spread in a prion-like manner as revealed by several in vitro and in vivo studies. The possible mechanism of Tau spread can be via bulk endocytosis of misfolded Tau species. The recent studies elucidating this mechanism have mainly focussed on the aggregation and spread of repeat domain of Tau in the cell culture models. Further studies are needed to elucidate the prion-like propagation property of full-length Tau and its aggregates in a more intense manner in vitro as well as in vivo conditions. Varied post-translational modifications can have discrete effects on aggregation propensity of Tau as well as its propagation. Here, we review the prion-like properties of Tau and hypothesize the role of glycation in prion-like properties of Tau. This post-translationally modified Tau might have an enhanced propagation property due to differential properties conferred by the modifications.
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10.1007/s12031-018-1111-5
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pubmed_89_81
|
BACKGROUND
Type I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life. Albumin linked to a protein will prolong the half-life of the linked protein.
METHODS
In this study, we explored the fusion of albumin to IFNβ (Alb-IFNβ) for its functional activity both in vitro and in vivo. We determined the half-life of Alb-IFNβ following treatment in the serum, tumor, and tumor draining lymph nodes in both wild type and FcRn knockout mice. We characterized the ability of Alb-IFNβ to enhance antigen-specific CD8+ T cells using ovalbumin (OVA) or human papillomavirus (HPV) E7 long peptides. Next, we evaluated the therapeutic antitumor effect of coadministration of AlbIFNβ with antigenic peptides against HPVE7 expressing tumor and the treatment's ability to generate HPVE7 antigen specific CD8+ T cells. The contribution of the antitumor effect by lymphocytes was also examined by an antibody depletion experiment. The ability of Alb-IFNβ to serve as an adjuvant was tested using clinical grade therapeutic protein-based HPV vaccine, TACIN.
RESULTS
Alb-IFNβ retains biological function and does not alter the biological activity of IFNβ. In addition, Alb-IFNβ extends half-life of IFNβ in serum, lymph nodes and tumor. The coadministration of Alb-IFNβ with OVA or HPVE7 antigenic peptides enhances antigen-specific CD8 +T cell immunity, and in a TC-1 tumor model results in a significant therapeutic antitumor effect. We found that CD8 +T cells and dendritic cells, but not CD4 +T cells, are important for the observed antitumor therapeutic effect mediated by Alb-IFNβ. Finally, Alb-IFNβ served as a potent adjuvant for TA-CIN for the treatment of HPV antigen expressing tumors.
CONCLUSIONS
Overall, Alb-IFNβ serves as a potent adjuvant for enhancement of strong antigen-specific CD8 +T cell antitumor immunity, reduction of tumor burden, and increase in overall survival. Alb-IFNβ potentially can serve as an innovative adjuvant for the development of vaccines for the control of infectious disease and cancer.
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10.1136/jitc-2021-004342
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pubmed_210_20517
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The raw datasets of oxysterol quantifications from whole cell and mitochondrial fractions of THP-1 monocytes and macrophages, neuronal-like SH-SH5Y cells and human peripheral blood mononuclear cells are presented. Oxysterols were quantified using a new liquid chromatography-mass spectrometry (LC-MS) and multiple reaction monitoring analysis published in the article "A quantitative LC-MS/MS method for analysis of mitochondrial-specific oxysterol metabolism" in Redox Biology [1]. This method showed improved extraction efficiency and recovery of mono and dihydroxycholesterols from cellular matrix. The datasets derived from the three cell lines are included in the appendix. These datasets provide new information about the oxysterol distribution in THP-1 monocytes and macrophages, SH-SY5Y cells and peripheral blood mononuclear cells. These datasets can be used as a guide for oxysterol distribution in the three cell lines for future studies, and can used for future method optimization, and for comparison of oxysterol recovery with other analytical techniques.
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10.1016/j.dib.2020.106382
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pubmed_172_1753
|
Between October 30 and November 5, 1980, the Professional Association of Interns and Residents of Ontario called a strike of house staff in Ontario's teaching hospitals. The authors obtained data concerning utilization of laboratory tests and radiology procedures during that period and for the same days 2 weeks before and after the strike. During the strike period, the number of tests performed per patient day decreased by only 8.3%. After accounting for proportional changes in emergency and nonemergency admissions, there was no significant change in the number of tests or relative value units performed per patient day as a result of the strike. These results suggest that the volume of tests performed in teaching hospitals is more likely related to the case mix and severity of illness of patients admitted to these institutions than to a pure "teaching effect."
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10.1097/00005650-198606000-00007
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pubmed_1133_15989
|
This study examined the recent level, trends and determinants of consanguineous marriage in Jordan using time-series data from the Jordan Population and Family Health Surveys (JPFHSs). According to the 2012 JPFHS, 35% of all marriages were consanguineous in Jordan in 2012. There has been a declining trend in consanguinity in the country, with the rate decreasing from a level of 57% in 1990. Most consanguineous marriage in 2012 were first cousin marriages, constituting 23% of all marriages and 66% of all consanguineous marriages. The data show that women with a lower age at marriage, older marriage cohort, larger family size, less than secondary level of education, rural place of residence, no employment, no exposure to mass media, a monogamous marriage, a husband with less than higher level of education and lower economic status, and those from the Badia region, were more likely to have a consanguineous marriage. Increasing age at marriage, level of education, urbanization and knowledge about the health consequences of consanguinity, and the ongoing socioeconomic and demographic transition in the country, will be the driving forces for further decline in consanguinity in Jordan.
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10.1017/S0021932017000372
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pubmed_821_18680
|
Neuregulin-1 proteins and their receptors, which are members of the ErbB subfamily of receptor tyrosine kinases, play essential roles in the development of the nervous system and heart. Most neuregulin-1 isoforms are synthesized as transmembrane proproteins that are proteolytically processed to yield an N-terminal fragment containing the bioactive EGF-like domain. In this study we investigated whether neuregulins are found in lipid rafts, membrane microdomains hypothesized to have important roles in signal transduction, protein trafficking, and proteolytic processing. We found that 45% of a 140-kDa neuregulin protein in rat brain synaptosomal plasma membrane fractions was insoluble in 1% Triton X-100. Flotation gradient analysis demonstrated the presence of the brain 140 kDa neuregulin protein in low-density fractions enriched in PSD-95, a known lipid raft protein. In transfected cells expressing the neuregulin I-beta 1a or the III-beta 1a isoform, most of the neuregulin proprotein was insoluble in 1% Triton X-100, and neuregulin proproteins and C-terminal fragments were detected in lipid raft fractions. In contrast, the III-beta 1a N-terminal fragment was detected only in the detergent-soluble fraction. These results suggest that localization of neuregulins to lipid rafts may play a role in neuregulin signaling within the nervous system.
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10.1046/j.1471-4159.2001.t01-1-00132.x
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pubmed_872_9662
|
OBJECTIVES
Food choice in schoolchildren was examined in relation to dieting and measures of eating psychopathology. It was predicted that dieters would make healthier food choices compared to non-dieters and that measures of eating psychopathology would be associated with food choice.
DESIGN
A cross-sectional questionnaire design incorporating an established adapted recall method was used to assess patterns of food consumption.
METHODS
Questionnaires were administered in 13 state secondary schools. Measures included a food frequency questionnaire, the Children's Eating Attitudes Test (CHEAT), body satisfaction ratings, dietary restraint, and questions about dieting status. The sample consisted of 574 females and 445 males aged 11-16 years.
RESULTS
Females made significantly more healthy food choices compared to males. Females reported dieting more than males (35% vs. 18%, respectively), and female dieters made more healthy food choices than female non-dieters. Almost a fifth (19%) of the entire sample reported skipping breakfast, with female dieters being three times more likely to do so than non-dieters. There were small but significant associations between reported food consumption and measures of eating attitudes, body dissatisfaction and restraint. For females who scored in the at-risk range on the CHEAT (8.7%), these associations were more substantial.
CONCLUSIONS
Female dieters appear to make more healthy food choices than non-dieters and so may be tuning into healthy eating messages more effectively. Vulnerable females may use 'healthy eating' to hide risky weight reduction behaviours. Further studies are required to examine the nutritional impact of moderate and extreme dieting in this age group.
|
10.1348/135910703770238301
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pubmed_1081_5936
|
Targeted therapy is one of the major treatment modalities in advanced non-small cell lung cancer (NSCLC) with sensitive driver gene mutations. BRAF is considered a promising oncogenic driver in NSCLC after the discovery of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion and ROS1 rearrangement. BRAF V600E mutation accounts for more than half of BRAF mutations, which is a potential therapeutic target for advanced NSCLC. This review aims to summarize the advancements of BRAF gene mutation and targeted therapy for BRAF mutation in NSCLC.
.
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10.3779/j.issn.1009-3419.2018.08.10
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pubmed_210_8980
|
AIM
This study aims to determine the causes of vaccine mistrust among family healthcare professionals (FHP) in the unit where they serve and vaccine hesitancy of families.
METHOD
The study group consisted of 682 FHPs working in a primary health care institution. The data collection tools of the study included a sociodemographic data form and a vaccine hesitancy data form. Pearson's chi-square analysis and logistic regression analysis were performed to analyze the data.
FINDINGS
To the question of "Do you trust the active ingredient in the vaccines?", only 2.1% of FHPs responded "I do not trust" and 18.9% answered "I am indecisive". 70.7% of FHPs said that at least one vaccine hesitant family was in the unit where they served. The most important reasons stated by FHPs on behalf of such families were vaccine mistrust (73.2%), the belief that they may be harmful for the child (58.7%), and the belief that vaccines cause autism (55.6%). In the univariate analysis, vaccine mistrust was significantly higher in FHPs who were measles-hesitant and responded "The decision to get vaccinated or not should belong to the family voluntarily". From logistic regression analysis, vaccine mistrust in FHPs increased 2.8-fold for those who did not think vaccination should be compulsory, 2.7-fold for those who did not think that vaccination refusal should be legally enforced, and 1.61-fold for those under age 35 years.
CONCLUSION
It was observed that FHPs had high sensitivity and positive attitudes toward vaccination in general.
|
10.1080/21645515.2020.1806671
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pubmed_489_23604
|
We report the 4,385,577-bp high-quality draft assembly of the bacterial symbiont Rhodococcus rhodnii strain LMG5362, isolated from the gut of Rhodnius prolixus (Hemiptera, Reduviidae, Triatominae), the principle vector of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. This sequence might provide useful information for subsequent studies of the symbiotic relationship between Rd. prolixus and Rc. rhodnii, while also providing a starting point for the development of biotechnological applications for the control of Rd. prolixus.
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pubmed_489_23604
|
pubmed_622_11782
|
OBJECTIVES
To formulate reference charts and equations for estimated fetal weight (EFW) from a large sample of fetuses and to compare these charts and equations with those obtained for birth weight during the same study period and in the same single health authority.
METHODS
Biometric data were obtained at 20-36 weeks' gestation from routine screening examinations spanning 4 years. Exclusion criteria were a known abnormal karyotype or congenital malformation and multiple pregnancy. No data were excluded on the basis of abnormal biometry. EFW was calculated based on Hadlock's formula. We used a polynomial regression approach (mean and SD model) to compute a new reference chart for EFW. This chart was compared with that of birth weight at 25-36 weeks' gestation during the same study period and in the same health authority.
RESULTS
18,959 fetuses were included in the study. New charts and equations for Z-score calculations at 20-36 weeks' gestation are reported. Comparison with the birth-weight chart showed that the EFW was noticeably larger at 25-36 weeks' gestation. At 28-32 weeks' gestation, the 50th centile for birth weight compared approximately with the 10th centile for EFW.
CONCLUSION
We present new reference charts and equations for EFW. EFW is computed throughout gestation based on measurements in healthy fetuses. However, before full term, birth-weight charts reflect a significant proportion of growth-restricted fetuses that deliver prematurely. We provide additional evidence that comparing EFW with birth-weight charts is misleading.
|
10.1002/uog.4019
|
pubmed_733_13898
|
A prospective study evaluated and compared midazolam versus diazepam in the upper gastrointestinal endoscopy. Patients were excluded if they had experienced any of the following: intolerance to benzodiazepines, pregnancy, alcohol or drug addiction, and weakness chronic disease. Seventy one patients were assigned to two groups: 36 received diazepam (0,15 Mg/Kg. intravenous) and 35 midazolam (0,07 mg/kg.). Patients in the two study group were similar in regard to demographic data (sex, age, and weight). Midazolam resulted in a marked improvement of conscious sedation and the anxiolysis as compared with the group receiving diazepam (p<0.001). Amnesia were significantly more frequent in the midazolam group (total 77,14% and partial 17,14%) compared with diazepam group (total 11,11% and partial 2,77%). The present study show that midazolam improves patient tolerance lo endoscopy compared with diazepam (p<0.001).The selection of patients is very important, no clinically adverse events related to cardiopulmonary changes ocurred in any group.
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pubmed_733_13898
|
pubmed_307_18278
|
INTRODUCTION
Bladder cancer is the second most common malignancy of urologic tumors. Back in 1976, lasers were added to the endourological armetarium for bladder tumor treatment. Despite nowadays' standard procedure for staging and treating non-muscle invasive bladder tumor by transurethral resection of bladder tumors (TURB) via a wire loop, laser resection techniques for bladder tumor came back in focus with the introduction of Ho:YAG and not to mention recently Tm:YAG lasers. This review aims to display the current evidence for these techniques.
MATERIALS AND METHODS
Throughout April 2010, MEDLINE and the Cochrane central register of controlled trials were searched previously for the following terms: "Laser, resection, ablation, coagulation, Nd:YAG Neodym, HoYAG: Holmium, Tm:YAG Thulium and transitional carcinoma, bladder, intravesical."
RESULTS
Eleven articles on Ho:YAG and 7 on Tm:YAG were identified. Searches by Cochrane online library resulted in no available manuscripts.
CONCLUSION
Today, Nd:YAG does not play any role in treatment of lower urinary tract transitional cell carcinoma. Ho:YAG and Tm:YAG seem to offer alternatives in the treatment of bladder cancer, but still to prove their potential in larger prospective randomized controlled studies with long-term follow-up. Future expectations will show whether en bloc resection of tumors are preferable to the traditional "incise and scatter" resection technique, in which is contrary to all oncological surgical principles. For the primary targets, here are within first-time clearance of disease, in addition to low in-fields and out-of-fields recurrence rates.
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10.1007/s00345-011-0680-5
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pubmed_142_4079
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Identification of catalytic residues can help unveil interesting attributes of enzyme function for various therapeutic and industrial applications. Based on their biochemical roles, the number of catalytic residues and sequence lengths of enzymes vary. This article describes a prediction approach (PINGU) for such a scenario. It uses models trained using physicochemical properties and evolutionary information of 650 non-redundant enzymes (2136 catalytic residues) in a support vector machines architecture. Independent testing on 200 non-redundant enzymes (683 catalytic residues) in predefined prediction settings, i.e., with non-catalytic per catalytic residue ranging from 1 to 30, suggested that the prediction approach was highly sensitive and specific, i.e., 80% or above, over the incremental challenges. To learn more about the discriminatory power of PINGU in real scenarios, where the prediction challenge is variable and susceptible to high false positives, the best model from independent testing was used on 60 diverse enzymes. Results suggested that PINGU was able to identify most catalytic residues and non-catalytic residues properly with 80% or above accuracy, sensitivity and specificity. The effect of false positives on precision was addressed in this study by application of predicted ligand-binding residue information as a post-processing filter. An overall improvement of 20% in F-measure and 0.138 in Correlation Coefficient with 16% enhanced precision could be achieved. On account of its encouraging performance, PINGU is hoped to have eventual applications in boosting enzyme engineering and novel drug discovery.
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10.1371/journal.pone.0135122
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pubmed_1119_15950
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Glucocorticoids (GC) inhibit IL-2 gene transcription by interfering with the binding of the nuclear factor activator protein-1 on the IL-2 promoter. Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is an essential component of the T cell antigen receptor signal transduction pathway leading to IL-2 gene transcription. Therefore, we have asked whether this phosphatase may also be regulated by GC. Jurkat T cells were cotransfected with plasmids containing the intact IL-2 promoter or its NF-AT and Oct-1 motifs, and a deletion mutant (delta CaM-AI) of calcineurin known to have Ca(2+)-independent constitutive phosphatase activity. Cotransfection of IL-2 promoter with delta CaM-AI allowed the activation of IL-2 promoter in the presence of phorbol ester alone. Under these conditions dexamethasone (Dex; 10(-6) M) inhibited IL-2 promoter activation by 50-60%. The inhibitory effect of Dex was specific, as demonstrated by experiments using an unrelated promoter (simian virus 40) and estradiol. Furthermore, it was completely reversed in the presence of excess amounts of the glucocorticoid antagonist RU 486, which suggests that it is mediated through the glucocorticoid receptor. Overexpression of calcineurin via delta CaM-AI in Jurkat cells decreased their apparent sensitivity to Dex (approximately 5-fold increase in IC50). Similar results were obtained with the NF-AT and Oct-1 constructs, which are also known to be activated by calcineurin. Thus, in addition to their known inhibitory effects on activator protein-1, GC also inhibit calcineurin-dependent pathways for T cell activation.
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pubmed_1119_15950
|
pubmed_98_23009
|
Heuristic and machine learning models for rank-ordering reaction templates comprise an important basis for computer-aided organic synthesis regarding both product prediction and retrosynthetic pathway planning. Their viability relies heavily on the quality and characteristics of the underlying template database. With the advent of automated reaction and template extraction software and consequently the creation of template databases too large for manual curation, a data-driven approach to assess and improve the quality of template sets is needed. We therefore systematically studied the influence of template generality, canonicalization, and exclusivity on the performance of different template ranking models. We find that duplicate and nonexclusive templates, i.e., templates which describe the same chemical transformation on identical or overlapping sets of molecules, decrease both the accuracy of the ranking algorithm and the applicability of the respective top-ranked templates significantly. To remedy the negative effects of nonexclusivity, we developed a general and computationally efficient framework to deduplicate and hierarchically correct templates. As a result, performance improved considerably for both heuristic and machine learning template ranking models, as well as multistep retrosynthetic planning models. The canonicalization and correction code is made freely available.
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10.1021/acs.jcim.1c01192
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pubmed_1072_966
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Background A key element for an effective and safe oral anticoagulant treatment (OAT) is to have the relevant information delivered to patients in an easy-to-understand way and thus have them apply this knowledge in their own therapy. Objective To assess knowledge about OAT, reveal knowledge gaps and identify at-risk patients in terms of limited knowledge about their anticoagulant therapy. Setting Community pharmacies in Hungary. Methods This descriptive cross-sectional study used a structured, validated, self-developed questionnaire to assess patients' knowledge about OAT. Scores were calculated on each domain and the association between knowledge and patients' or treatment characteristics were analysed. Responses in all domains were assessed to identify at-risk patients and knowledge gaps. Main outcome measures Knowledge and knowledge gaps on OAT, and risk factors for limited knowledge. Results The questionnaire developed based on four validated questionnaires passed the field test and had a good internal consistency (Cronbach α = 0.795). Our full patient population (N = 427) had a mean percentage score of 59.39 (29.7% good, 41.2% average, 29.0% poor knowledge on OAT). Poor knowledge level was found to significantly correlate with advanced age (> 75 years), lower education, diagnosis of atrial fibrillation, and unawareness of the indication of OAT. The lowest frequency of correct answers regarded the questions on drug interactions (10.2%) and diet (11.4%). Pharmacists were infrequently indicated as the healthcare professionals to share information with regarding OAT (12.7%). Conclusion Findings of our study offer a valuable insight into the required directions of developing new strategies for patient education to improve knowledge on the treatment with oral anticoagulants.
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10.1007/s11096-017-0544-1
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pubmed_783_1338
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Haemorrhagic transformation (HT) of ischaemic infarction occurs when an area of brain infarction is stained with blood products, mainly red blood cells. An abnormally permeable blood-brain barrier resulting from ischaemia of the capillary endothelium allows this extravasation of blood products. HT is part of the natural history of some forms of ischaemic infarction, especially cerebral embolism, but it can be precipitated or enhanced by therapeutic interventions used in the acute phase of ischaemic stroke. The old view of HT after cerebral embolism as a generally asymptomatic change in a tissue that is already necrotic has been challenged by observations from therapeutic thrombolysis that suggest that HT can have a negative effect on patients' outcomes. Understanding of the risk factors for and the underlying mechanisms and clinical variability of HT in the context of acute therapeutic interventions in ischaemic stroke could help in the early detection of this complication, in determining the safety of recanalisation approaches, and in setting the stage for future research into the prevention or treatment of HT in patients with acute ischaemic stroke.
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pubmed_783_1338
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pubmed_386_5256
|
New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT=tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp(3)-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I). These findings were supported by results from the 60-cell line fingerprint screen of the Developmental Therapeutics Programme of the National Institutes of Health for two promising compounds. The cytotoxicity of some of these ligands and gold(I)complexes is due to the induction of apoptosis. The ligands and gold(I)complexes demonstrated selective toxicity towards specific cell lines, with Jurkat T cells being more sensitive to the cytotoxic effects of these compounds, while the non-cancerous human cell line KMST6 proved more resistant when compared to the cancerous cell lines. Results from the NIH DTP 60 cell-line fingerprint screen support the observed enhancement of cytotoxicity upon gold(I) complexation. One gold(I)complex induced high levels of apoptosis at concentrations of 50 μM in all the cell lines screened in this study, while some of the other compounds selectively induced apoptosis in the cell lines. These results point towards the potential for selective toxicity to cancerous cells through the induction of apoptosis.
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pubmed_386_5256
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pubmed_713_7531
|
BACKGROUND
People with cystic fibrosis (pwCF) derive several physiological and psychological benefits from regular physical activity (PA), but the practice is lower than recommended. Knowledge about the facilitators of and barriers to PA at the individual level is important to act positively on PA behaviors. This study validated the Cystic Fibrosis Decisional Balance for Physical Activity scale (CF-DB-PA) for adults with CF.
METHODS
French adults with CF were recruited in several specialist centres in France. The CF-DB-PA scale was validated following a quantitative study protocol comprising four stages: (1) tests of the clarity and relevance of a preliminary 44-item version and reduction analysis, (2) confirmatory factor analysis and tests of dimensionality through equation modelling analysis, (3) tests of reliability with Cronbach alphas for the internal consistency and a test-retest with a 2-to-3 week interval for temporal stability, and 4) tests of construct validity with Spearman correlations to measure the associations between each subscale and the theoretically related constructs (i.e., quality of life, PA and exercise tolerance).
RESULTS
A total of 201 French adults with CF participated in the validation study. The CF-DB-PA comprises 23 items divided into two factors: facilitators of and barriers to PA. Each factor is divided into three subscales: physical, psychological and environmental. The factors (facilitators and barriers) can be used independently or combined as a whole. A general score of decisional balance for PA can also be calculated. The bi-factor model presented satisfactory adjustment indexes: χ2 (194) = 362.33; p < .001; TLI = .87; CFI = .90; RMSEA = .067. The scale showed satisfactory internal consistency (Cronbach's α = .77). The test-retest reliability was not significant for either subscale, indicating stability over time. The facilitators subscale correlated significantly with the self-reported score of PA (r = .33, p < .01) and quality of life (r = .24, p < .05). The barriers subscale correlated significantly with the self-reported scores of PA (r = - .42, p > .01), quality of life (r = - .44, p < .01), exercise tolerance (r = - .34, p < .01) and spirometry tests (r = - .30, p < .05).
CONCLUSIONS
The CF-DB-PA is a reliable and valid questionnaire assessing the decisional balance for PA, the facilitators of and the barriers to PA for adults with CF in French-speaking samples.
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10.1186/s12890-021-01471-0
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pubmed_810_15212
|
Edible films may act as carriers of active molecules, such as flavors. This possibility confers to them the status of active packaging. Two different film-forming biopolymers, gluten and ι-carrageenans, have been compared. D-Limonene was added to the two film formulations, and its release kinetics from emulsion-based edible films was assessed with HS-SPME. Results obtained for edible films were compared with D-limonene released from the fatty matrix called Grindsted Barrier System 2000 (GBS). Comparing ι-carrageenans with gluten-emulsified film, the latter showed more interesting encapsulating properties: in fact, D-limonene was retained by gluten film during the process needed for film preparation, and it was released gradually during analysis time. D-Limonene did not show great affinity to ι-carrageenans film, maybe due to high aroma compound hydrophobicity. Carvone release from the three different matrices was also measured to verify the effect of oxygen barrier performances of edible films to prevent D-limonene oxidation. Further investigations were carried out by FT-IR and liquid permeability measurements. Gluten film seemed to better protect D-limonene from oxidation. Gluten-based edible films represent an interesting opportunity as active packaging: they could retain and release aroma compounds gradually, showing different mechanical and nutritional properties from those of lipid-based ingredients.
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10.1021/jf303327n
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pubmed_944_11282
|
Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the in vitro metabolism in Sprague-Dawley rat liver microsomes of forsythoside A were investigated. The observations from Sprague-Dawley rat liver microsomes in the presence of β-NADPH or UDPGA that forsythoside A may be the substrates of CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3, UGT1A1 and UGT1A9; Chlorogenic acid may be the substrates of CYP3A4, CYP2C9, CYP1A2, CYP2C19, UGT1A6, UGT1A3 and UGT1A1; Baicalin may be the substrates of CYP3A4, CYP2C19, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; Baicalein may be the substrates of CYP3A4, CYP2E1 and UGT1A6. It was also found that the residue of forsythoside A in SHL, FF+LJF and FF+SR was greatly increased compared with that in FF in Sprague-Dawley rat liver microsomes in the presence of β-NADPH or UDPGA, which indicated that the metabolism of forsythoside A in SHL may be influenced by chlorogenic acid in LJF acting on the CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3 and UGT1A1; baicalin in SR acting on the CYP3A4, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; baicalein acting on the CYP3A4 and UGT1A6 respectively.
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10.1016/j.fitote.2011.08.009
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pubmed_1005_20220
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Lamium album and Lamium purpureum are species belonging to the genus Lamium. Aerial parts of the two species and roots of Lamium album have applications in human and veterinary traditional medicine. Haemostatic properties of butanolic extracts of Lamium species were investigated by two experimental models in Wistar rats: haemostatic test by tail bleeding time determination and acenocoumarolcarrageenan test. Results of the haemostatic test by tail bleeding determination demonstrated haemostatic activity of both extracts. In the acenocoumarol-carrageenan test, only the Lamium album extract showed haemostatic activity, comparable to that of vitamin K. Based on the qualitative chemical data on iridoid glycosides (HPTLC), 8-acetylshanzhiside methyl ester might be assumed to be responsible for haemostatic activity. Based on the acute toxicity test, none of the extracts showed toxicity.
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pubmed_1005_20220
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pubmed_840_13324
|
We report the case of a 56-year-old Japanese man with Vogt-Koyanagi-Harada disease in whom pain and diffuse swelling of the left auricle and bilateral episcleritis developed 3 years after diagnosis. Biopsy of the left ear showed acute chondritis, leading to another diagnosis of relapsing polychondritis. Additionally, he was found to carry human leukocyte antigen DR4, which has been reported to be associated with these inflammatory conditions. To our knowledge, our patient is the first reported case of the occurrence of relapsing polychondritis and Vogt-Koyanagi-Harada disease.
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10.1007/s10165-005-0388-8
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pubmed_603_10105
|
Mitochondria and Fas (CD95) play a role in tumorigenicity and apoptosis. In the present study, the functional relationship of mitochondria to Fas in mediating apoptosis was investigated. Glioblastoma cells (DBTRGO5MG, U87) were depleted of mitochondrial DNA (mtDNA) by treatment with ethidium bromide (Rho(-) cells). Compared to Rho(+) cells, Rho(-) cells showed enhanced expression of Fas at the cell surface. Indeed, when Rho(+) cells were treated with mitochondrial respiratory chain complex inhibitors, Fas cell surface expression was noted to increase in a similar fashion to the depletion of mtDNA in both cell lines. However, when cells were evaluated for sensitivity to apoptosis using Fas-engagement, there was no difference between the Rho(+) and Rho(-) cells in either cell line. By contrast, sensitivity to the cytotoxic agent cis-diammine-dichloroplatinum (cisplatin) was markedly increased in the Rho(-) cells, which expressed higher levels of cell surface Fas. Expression of Fas is increased with the depletion of mtDNA and respiratory complex inhibitors. However, this increase in expression does not necessarily translate to an increase in sensitivity to Fas-engagement, although there is an increase in the sensitivity of depleted cells to cytotoxic agents such as cisplatin.
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10.3892/etm.2010.158
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pubmed_118_23333
|
BACKGROUND
Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined.
METHODS
In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O2 exposure at acute and chronic time points.
RESULTS
In response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O2. Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect.
CONCLUSIONS
This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs.
|
10.1186/s13287-016-0430-0
|
pubmed_983_14962
|
H. pylori is a human pathogen that colonizes the epithelium of the stomach. The host immune response may influence the disease process, where cytokines play important roles in the development of disease. In this study, the concentrations of selected cytokines in the gastric antrum and stomach body mucosa and also in the serum were evaluated. Eighty patients according to their rapid urease test were divided into two groups: H. pylori positive (n=39) and H. pylori-negative (n=41). The concentrations of cytokines in biopsies and serum were determined by ELISA method. The mean TNF-α and IFN-γ levels in the infected group were significantly higher than that of uninfected patients. In contrast, IL-10 level in most patients was undetectable. The mean antral of stomach TNF-α and IFN-γ levels were significantly higher than that of the stomach body. IFN-γ serum level showed positive correlation with antrum and stomach body levels, whereas no correlation was found in TNF-α in different samples. Higher levels of TNF-α and IFN-γ in antral indicate that the colonization of bacteria in the antrum may be higher than stomach body (culture results from two sites support this statement). Increased serum level of IFN-γ indicates the activation of circulating-T cells against infection. Induced H. pylori-related TNF-α is concentrated is gastric mucosa and this pathogen does not cause any significant change in the serum level of this cytokine. Therefore H. pylori by inducing certain inflammatory cytokines but not IL-10 may contribute the process of disease development.
|
010.04/ijaai.267271
|
pubmed_238_7660
|
(1) Background: Bacitracin is a broad spectrum antibiotic that is used against various microorganisms. Chitosan is a natural polymer that has been widely investigated as an antimicrobial agent for preventing and treating infections owing to its intrinsic antimicrobial properties, as well as its ability to effectively deliver extrinsic antimicrobial compounds to infected areas. Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of administered compounds/drugs. The topical use of chitosan-decorated bacitracin-loaded cream improves the permeation of the drug across the skin and enhances the drug bioavailability by prolonging the residence time of the drug when applied topically, as well as producing synergistic effects and reducing the side effects of the drug. Topical chitosan-decorated cream can be a promising approach to administer the drug more efficiently and enhance the efficacy of treatment in wound healing and antibacterial activity. (2) Methods: This study was conducted to prepare, assess and investigate the synergistic antibacterial activity of a chitosan-coated bacitracin cream. The results were compared to the antibacterial activity of simple bacitracin-loaded cream. The prepared cream was evaluated for various in vitro characteristics such as rheology, pH, viscosity, drug content and antibacterial activity studies. (3) Result: The formulations were found to be stable regarding color, liquefaction and phase separation at all accelerated conditions. It was observed that with time, substantial variations in the pH of the preparations were found. The introduction of chitosan results in controlled release of the drug from the formulations. The antibacterial activity of the formulated creams was assessed with the disc diffusion method against Staphylococcus aureus(ATCC),Escherichiacoli (STCC),Pseudomonas aeruginosa(ATCC) and Bacillus cereus(ATCC). The strains, E. coli, S. aureus, P. aeruginosa and B. cereus were susceptible to 50 µg chitosan-decorated bacitracin cream, showing inhibition zones of 10 ± 0.6, 34 ± 1.5, 31 ± 0.76 and 21 ± 2.02 mm, respectively. The zones of inhibition for simple bacitracin-loaded cream were significantly smaller than chitosan-decorated cream, at 2 ± 0.2, 28 ± 0.92, 15 ± 0.5 and 11 ± 1.25 mm (ANOVA; p < 0.05), respectively. (4) Conclusion: It was observed that the zones of inhibition of simple bacitracin-loaded cream were significantly smaller than those of chitosan-decorated bacitracin-loaded cream. Chitosan synergistically improves the antimicrobial activity of bacitracin. Hence, the developed formulation was effective and should be considered as a suitable candidate for topical management of skin infections and wound healing.
|
10.3390/antibiotics11091151
|
pubmed_1075_7635
|
The synthetic mesh is widely used for treatment of hernias. We conducted a comparative study of the morphological pattern of inflammation, the cellular composition of tissues and dynamics of scar formation in mice when using implants "Esfil" and "Unifleks" under influence of single and double injection of cultured fibroblast and without such injection to the region of stents location. A more pronounced inflammatory reaction during the study period of investigation was observed in the case of "Esfil". In the late period of the study, a higher percentage of fibroblasts was observed in the case of the prosthesis "Unifleks" compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies the curve of the dynamics of the inflammatory process by making it smoother in the case of both prostheses. So, more preferred is the use of prostheses "Unifleks".
|
pubmed_1075_7635
|
pubmed_707_9473
|
Transforming growth factor (TGF)-β1 and prostaglandin E2 (PGE2) are humoral factors critically involved in the induction of immunosuppression in the microenvironment of various types of tumors, including melanoma. In this study, we identified a natural compound that attenuated TGF-β1- and PGE2-induced immunosuppression and examined its effect on B16 melanoma growth in mice. By screening 502 natural compounds for attenuating activity against TGF-β1- or PGE2-induced suppression of cytolysis in poly(I:C)-stimulated murine splenocytes, we found that betulin was the most potent compound. Betulin also reduced TGF-β1- and PGE2-induced downregulation of perforin and granzyme B mRNA expression and cell surface expression of NKG2D and CD69 in natural killer (NK) cells. Cell depletion and coculture experiments showed that NK cells, dendritic cells, B cells, and T cells were necessary for the attenuating effects of betulin. Structure-activity relationship analysis revealed that two hydroxyl groups at positions C3 and C28 of betulin, their cis-configuration, and methyl group at C30 played crucial roles in its attenuating activity. In a subcutaneous implantation model of B16 melanoma in mice, intratumor administration of betulin and LY2157299, a TGF-β1 type I receptor kinase inhibitor, significantly retarded the growth of B16 melanoma. Notably, betulin increased significantly the number of CD69 positive NK cells in tumor sites at early stages of post-tumor cell injection. Our data suggest that betulin inhibits the growth of B16 melanoma by enhancing NK cell activity through attenuating the immunosuppressive tumor microenvironment.
|
10.1248/bpb.b21-00921
|
pubmed_735_2373
|
Mesonephric carcinoma of the uterine corpus is an extremely rare malignancy that originates from the mesonephric remnant of the female reproductive tract. There have been no previous reports of mesonephric carcinoma accompanied by a sarcomatous component. The current study presents two cases of uterine corpus mesonephric carcinoma with sarcomatous components that occurred in postmenopausal women. Immunohistochemically, the tumour cells were positive for vimentin and CD10. The tumours of these patients were located in the uterine myometrium; therefore, treatment was similar to that for endometrial cancer. Although the follow-up period was short in the current cases, no metastatic disease was identified in the second case and thus, this may increase clinical knowledge with regard to the biological behavior of these rare malignancies.
|
10.3892/ol.2015.3886
|
pubmed_595_5631
|
BACKGROUND
Sympathetic activity mediated by adrenergic receptors (ARs) appears to play an important role in controlling the vasomotor tone and, thus, may be associated with vasospastic angina (VA). We investigated the association of the common functional polymorphisms of the AR gene and VA. The candidates were alpha2CDel322-325, beta1Gly389Arg, beta2Arg16Gly, and beta2Gln27Glu polymorphisms.
METHODS
Eighty-two patients with VA, confirmed by coronary angiography with or without ergonovine provocation test, and 114 apparently healthy control subjects were investigated for genotype of 4 AR polymorphisms and established risk factors of ischemic heart disease.
RESULTS
The minor alleles were alpha2CDel322-325, beta1Gly389, beta2Gly16, and beta2Glu27 and their frequencies were 7%, 18%, 42%, and 29%, respectively, in the control subjects of this Korean population, which were different from those of other ethnic groups. On univariate analysis, age, smoking, male sex, alpha2CDel322-325 allele carrier state, and beta2Gln27 homozygote state were significant risk factors for VA. After multivariate analysis using multiple logistic regression model, age (odds ratio [OR] 1.809, CI 1.046-1.135, P < .0001), smoking (OR 4.902, CI 2.105-11.416, P = .0002), alpha2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P = .0003), and beta2Gln27 allele homozygosity (OR 3.152, CI 1.364-7.285, P = .0072) remained as independent risk factors. In the combined genotype analysis, the effect of beta2Gln27 allele was evident only when the alpha2CDel322-325 allele was absent.
CONCLUSIONS
The alpha2CDel322-325 allele carrier state and beta2Gln27 allele homozygote state were identified as novel risk factors of VA in this Korean population. This result suggests the importance of the adrenergic stimuli and the genetic background in the pathogenesis of the VA.
|
10.1016/j.ahj.2005.06.009
|
pubmed_876_14506
|
UNLABELLED
The purpose of this article is to review a large series of patients evaluated for disorders of the facial nerve in order to assess the indications for surgery, the timing of surgery, the techniques of nerve repair, and to better define those factors associated with a favorable outcome.
STUDY DESIGN
A retrospective review of patients undergoing facial nerve repair from 1963-1997.
METHODS
One hundred and three patients underwent surgical intervention designed to repair a disrupted facial nerve. All procedures were performed by one of the senior surgeons (M.M.) Seventy-two patients had a complete data set and at least one year of follow-up.
RESULTS
Eighty percent of patients attained an outcome considered superb to fair. Twenty percent of patients had a poor outcome. There was a slight worsening of outcome with increased time to repair. Patients with a neoplastic etiology of nerve paralysis tended to have a worse outcome.
CONCLUSIONS
Facial nerve grafting is most successful if intervention is undertaken at or near the time of initial injury. However, prolonged time (up to two years) to repair does not preclude the potential for some recovery. The limitations of the current systems for grading facial recovery after nerve repair are well known, and the adoption of a new grading scale for assessing recovery after reanimation procedure is recommended.
|
10.1055/s-2000-15545
|
pubmed_794_23904
|
The new techniques of genetic analysis have made it possible to identify many new forms of inherited thrombocytopenias (IT) and study large series of patients. In recent years, this has changed the view of IT, highlighting the fact that, in contrast to previous belief, most patients have a modest bleeding diathesis. On the other hand, it has become evident that some of the mutations responsible for platelet deficiency predispose the patient to serious, potentially lifethreatening diseases. Today's vision of IT is, therefore, very different from that of the past and the therapeutic approach must take these changes into account while also making use of the new therapies that have become available in the meantime. This review, the first devoted entirely to IT therapy, discusses how to prevent bleeding in those patients who are exposed to this risk, how to treat it if it occurs, and how to manage the serious illnesses to which patients with IT may be predisposed.
|
10.3324/haematol.2022.280856
|
pubmed_109_9564
|
SIADH consists of hyponatremia and hyposmolality, continued urinary loss of sodium, excretion of an inappropriately concentrated urine, and absence of dehydration, usually in the presence of normal renal and adrenal function. The retention of excess water caused by the inappropriate secretion of antidiuretic hormone is central to the development of the syndrome. In pediatrics, SIADH is most commonly seen in patients with meningitis or postoperatively. Fluid restriction is vital in such patients to prevent the development of symptomatic SIADH. Fluid restriction alone will also result in the correction of serum electrolyte composition in patients with SIADH. Hypertonic saline should be used only in severely symptomatic patients.
|
10.1016/s0031-3955(16)33353-3
|
pubmed_586_14492
|
An alkylating analogue of NADP+ the 3-chloroacetylpyridine adenine dinucleotide phosphate was prepared from 3-diazoacetylpyridine adenine dinucleotide phosphate which was obtained by enzymatic transglucosidation of NADP+. The 3-diazoacetylpyridine adenine dinucleotide phosphate proved to be more unstable when compared to the corresponding NAD+ analogue. The alkylation of several dehydrogenases using this alkylating analogue is mentioned.
|
10.1016/s0300-9084(78)80676-2
|
pubmed_68_485
|
An interleaved velocity-sensitised fast low-angle shot pulse sequence was used to study cerebrospinal fluid (CSF) flow in the cerebral aqueduct, and supratentorial CSF production in 9 patients with normal pressure hydrocephalus (NPH) and 9 healthy volunteers. The peak aqueduct CSF flow, both caudal and rostral, was significantly increased in patients with NPH. No significant difference in the supratentorial CSF production rate was found between patients (mean 0.60 +/- 0.59 ml/min) and healthy volunteers (mean 0.68 +/- 0.31 ml/min). Our method may be useful for investigation and monitoring of patients with NPH before and after ventriculoperitoneal shunt operations.
|
10.1007/BF00588133
|
pubmed_378_16068
|
As the waste industry continues to move from a disposal-based system to one based on a combination of recovery options, the need for information on the composition of waste increases and this is reflected by the amount of information on the physical composition of municipal solid wastes that is now available. However, there is far less information on the chemical composition of municipal solid waste. The results from a number of chemical surveys from Europe are compared and show a reasonable degree of agreement, but several problems were identified with the data. Chemical and physical compositional data are combined in a case study example to investigate the flow of key potential pollutants in an integrated solid waste management system that uses materials recycling, composting, incineration and landfilling. This case study has shown that an integrated waste management strategy diverts lead and cadmium away from composting and recycling to incineration, which effectively isolates these elements from the environment through efficient capture of the pollutants followed by secure landfilling or recycling of the residues. However, further work is needed to determine the distribution of mercury in incineration residues and its fate when the residues are landfilled.
|
10.1016/j.wasman.2005.12.020
|
pubmed_665_10613
|
A plant carrying a small extra chromosome was found in Landsberg erecta ecotype of Arabidopsis thaliana. Fluorescence in situ hybridization revealed that this minichromosome was derived from the short arm of chromosome 4. The size of this "mini4S" chromosome was estimated to be approximately 7.5 Mb on the basis of previously reported data and the amount of the centromeric major satellite (180-bp family) present, which was determined to be about 1 Mb, or about one third of that in the normal chromosome 4. No pairing between mini4S and its original chromosome 4 was observed at pachytene and metaphase I stages. The transmission of mini4S through pollen was limited, but about 30% of selfed progeny carried the mini4S chromosomes. The transmission rates considerably increased when the mini4S chromosomes were transferred to plants with a Columbia background by successive backcrosses. This suggests that the stability of the minichromosomes is controlled genetically by factors that can vary between ecotypes.
|
10.1007/s00412-005-0045-1
|
pubmed_487_17042
|
We have developed a new protocol for digesting hydrophobic proteins using trypsin with the aid of phase-transfer surfactants (PTS), such as sodium deoxycholate (SDC). SDC increases the solubility of hydrophobic proteins, enhances the activity of trypsin, and improves the accessibility to trypsin of proteins denatured during the extraction process. After digestion, SDC was successfully removed from the acidified solution containing tryptic peptides by adding a water-immiscible organic solvent, into which SDC was predominantly transferred, while the digested peptides remained in the aqueous phase. Compared with a protocol using an acid-labile surfactant, this PTS protocol increased the number of identified proteins and the recovery of hydrophobic peptides in the analysis of 400 ng of a membrane-enriched fraction of Escherichia coli. Application of the PTS protocol to 9.0 microg of a membrane-enriched pellet from human cervical cancer HeLa cells resulted in identification of a total of 1450 proteins, of which 764 (53%) were membrane proteins, by two-dimensional strong cation exchange (SCX)-C18 LC-MSMS with 5 SCX fractions. The distribution of the number of transmembrane domains in proteins identified in this study was in agreement with that in the IPI human database, suggesting that the PTS protocol can provide unbiased digestion of the membrane proteome.
|
10.1021/pr700658q
|
pubmed_563_274
|
Home working has increased due to COVID-19, but little is known about how this change has impacted the health risk behaviour of elevated sedentary time. The aim of this cross-sectional exploratory study was to assess occupational sitting behaviour when working at home, and use the Capability Opportunity Motivation-Behaviour (COM-B) model to identify influences on this behaviour. University staff (n = 267; 69% female; 92% white) who were predominantly working from home completed a questionnaire to assess sitting time, sitting breaks, demographic and occupational characteristics, and a 7-item COM-B questionnaire and open-ended questions to assess influences on time spent sitting whilst working from home. Data were analysed descriptively, a repeated measures ANOVA was used to determine differences in the COM-B items, and binary logistic regression was used to examine predictors of sitting time. Staff spent on average 89.5% (SD = 17.1) of their time sitting whilst working at home, and took an average of 1.36 (1.38) sitting breaks per hour. There were significant and meaningful differences in the influence of the COM factors on ability and willingness to reduce sitting behaviour (p < .0001; ηp 2 = .38), and the open-ended responses added further context. The included variables accounted for 20.7% of variance in sitting behaviour, with age, sitting breaks, motivation-automatic, and opportunity-physical contributing significantly. Working from home leads to elevated levels of sitting, and the COM-B provides a useful model to identify key influences on ability and willingness to reduce sitting. Strategies incorporating regular breaks, habit formation/reversal, and restructuring the physical environment may be beneficial.
|
10.1007/s41542-022-00128-6
|
pubmed_219_3799
|
Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding.
|
10.1371/journal.pone.0105707
|
pubmed_591_9653
|
Biological soil crusts across the desert regions play a key role in regional ecological security and ecological health. They are vital biotic components of desert ecosystems that maintain soil stability, fix carbon and nitrogen, influence the establishment of vascular plants, and serve as habitats for a large number of arthropods and microorganisms, as well as influencing soil hydrological processes. Changes in temperature and precipitation are expected to influence the functioning of desert ecosystems by altering biotic components such as the species composition of biological soil crusts. However, it remains unclear how these important components will respond to the prolonged warming and reduced precipitation that is predicted to occur with climate change. To evaluate how the hydrological properties of these biological soil crusts respond to these alterations, we used open-top chambers over a 10-year period to simulate warming and reduced precipitation. Infiltration, dew entrapment, and evaporation were measured as surrogates of the hydrological functioning of biological soil crusts. It was found that the ongoing warming coupled with reduced precipitation will more strongly affect moss in crustal communities than lichens and cyanobacteria, which will lead to a direct alteration of the hydrological performance of biological soil crusts. Reductions in moss abundance, surface cover, and biomass resulted in a change in structure and function of crustal communities, decreased dew entrapment, and increased infiltration and evaporation of biological soil crusts in desert ecosystems, which further impacted on the desert soil water balance.
|
10.1111/gcb.14378
|
pubmed_701_5576
|
While substance-abusing, schizophrenic populations have been the focus of recent research inquiries (Cuffel et al. 1993; Dixon et al. 1990; Drake et al. 1989; Miller and Tannenbaum, 1989; Mueser et al. 1990), few researchers have attempted to address the prevalence of drug and alcohol abuse among an urban, poor, predominantly minority schizophrenic patient group (Drake et al. 1989). Furthermore, we know of no published account that attempts to document, using ethnographic data, the strategies these patients use to acquire drugs and/or alcohol, and the lifestyles associated with such substance use. The majority of the patients in our research are African-American (roughly 80%) and almost all are on medical assistance, pointing to an indigent population with few external resources and little expendable income.
|
10.1080/00332747.1995.11024717
|
pubmed_1142_4181
|
Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1-T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend < 0.001). The adjusted OR [95% CI] of T1 and T2 in reference to T3 were 1.56 [1.09-2.23] and 1.19 [0.85-1.68] for high PCS and 1.19 [0.85-1.68] and 0.94 [0.68-1.29] for high MCS. Serum adiponectin level was inversely associated with physical HR-QOL in Korean pre-dialysis CKD patients. This relationship was independent of various cardiovascular risk factors.
|
10.1038/s41598-021-90339-8
|
pubmed_415_6749
|
The human brain undergoes structural changes in children entering puberty, while simultaneously children increase in height. It is not known if brain changes are under genetic control, and whether they are related to genetic factors influencing the amount of overall increase in height. Twins underwent magnetic resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High heritability estimates were found at both ages for height and brain volumes (49-96%), and high genetic correlation between ages were observed (r(g) > 0.89). With increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (-4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on average 13.8 cm in height (9.9%). Genetic influences on individual difference in volumetric brain and height changes were estimated, both within and across traits. The same genetic factors influenced both cerebral (20% heritable) and cerebellar volumetric changes (45%). Thus, the extent to which changes in cerebral and cerebellar volumes are heritable in children entering puberty are due to the same genes that influence change in both structures. The increase in height was heritable (73%), and not associated with cerebral volumetric change, but positively associated with cerebellar volume change (r(p) = 0.24). This association was explained by a genetic correlation (r(g) = 0.48) between height and cerebellar change. Brain and body each expand at their own pace and through separate genetic pathways. There are distinct genetic processes acting on structural brain development, which cannot be explained by genetic increase in height.
|
10.1002/hbm.21468
|
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