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pubmed_758_470
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The rat GST-P (placental glutathione S-transferase), a phase II detoxifying enzyme, is not expressed in normal liver cells, but is highly and specifically induced during early hepatocarcinogenesis as well as in hepatocellular carcinoma cells. Results of previous studies indicated that GST-P gene activation was mainly controlled by an enhancer element, GPE1 (GST-P enhancer 1), but the specific activation mechanism of the GST-P gene was not fully understood [Morimura, Suzuki, Hochi, Yuki, Nomura, Kitagawa, Nagatsu, Imagawa and Muramatsu (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2065-2068; Suzuki, Imagawa, Hirabayashi, Yuki, Hisatake, Nomura, Kitagawa and Muramatsu (1995) Cancer Res. 55, 2651-2655]. In the present study, we investigate the transcription factor Nrf2/MafK heterodimer (where Nrf2 stands for NF-E2 p45-related factor 2) as an activator of the GST-P gene through the action of GPE1 during hepatocarcinogenesis. Electrophoretic mobility-shift assay and footprinting analysis with wild-type GPE1 and GPE1 point mutants showed that the Nrf2/MafK heterodimer specifically bound GPE1. Reporter transfection assays indicated that Nrf2 strongly stimulated GST-P gene expression in mouse F9 embryonal carcinoma cells and H4IIE rat hepatoma cells. Northern-blot analysis indicated that GST-P and Nrf2 mRNA increased in parallel with development of precancerous lesions and hepatocellular carcinoma. Keap1 (Kelch-like ECH-associated protein 1), an inhibitory factor of Nrf2, decreased the activation of GPE1 by Nrf2 and this suppression was restored after treatment with electrophilic compounds. GST-P mRNA expression in H4IIE cells was induced by electrophilic compounds, as was the expression of mRNAs of other phase II detoxifying enzymes. Chromatin immunoprecipitation analyses showed that antibodies both against Nrf2 and against MafK precipitated GPE1 from the chromatin of the pre-neoplastic hepatocytes and rat hepatoma cells (H4IIE and dRLh84), but not from normal hepatocytes. These results indicate that the Nrf2/MafK heterodimer regulates GST-P gene expression during early hepatocarcinogenesis and in hepatoma cells.
|
10.1042/BJ20031948
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pubmed_568_8197
|
BACKGROUND
The relationship between guideline adherence for radical cystectomy of non-muscle-invasive bladder cancer and patient prognoses currently remains unclear. We investigated whether guideline adherence at the time of non-muscle-invasive bladder cancer affects the oncological outcomes of bladder cancer patients who underwent radical cystectomy.
METHODS
Among 267 cTa-4N0-2M0 bladder cancer patients, 70 who underwent radical cystectomy under the non-muscle-invasive bladder cancer or muscle-invasive bladder cancer status that progressed from non-muscle-invasive bladder cancer were identified. Patients who followed the guidelines from initial transurethral resection of bladder tumors to radical cystectomy were defined as the guideline adherent group (n = 52), while those who did not were the guideline non-adherent group (n = 18).
RESULTS
In the guideline non-adherent group, 8 (44.4%) out of 18 were diagnosed with highest risk non-muscle-invasive bladder cancer for Bacillus Calmette Guérin-naïve patients and 7 (38.9%) had a Bacillus Calmette Guérin unresponsive tumor status. Five-year recurrence-free survival and cancer-specific survival rates for the guideline non-adherent group vs guideline adherent group were 38.9% vs 69.8% (P = 0.018) and 52.7% vs 80.1% (P = 0.006), respectively. A multivariate analysis identified guideline non-adherence as one of independent indicators for disease recurrence (hazard ratio = 2.81, P = 0.008) and cancer-specific death (hazard ratio = 4.04, P = 0.003). In a subgroup analysis of 49 patients with cT1 or less non-muscle-invasive bladder cancer at the time of radical cystectomy, guideline non-adherence remained an independent prognostic factor for cancer-specific survival (hazard ratio = 3.46, P = 0.027).
CONCLUSIONS
Guideline adherence during the time course of the non-muscle-invasive bladder cancer stage may result in a favorable prognosis of patients who receive radical cystectomy. Even under non-muscle-invasive bladder cancer status, radical cystectomy needs to be performed with adequate timing under guideline recommendations.
|
10.1093/jjco/hyab060
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pubmed_715_20411
|
A reverse phase high performance liquid chromatographic method for quantitation of perillyl alcohol in a topical cream pharmaceutical formulation was developed. Previously reported methods for analyzing drugs in lipid formulations are relatively complex and time consuming, with extraction, purification and derivatization involved. Through a simple dilution of the cream formulation in isopropyl alcohol, the present assay method enables the direct injection of the samples, on an Alltima C18 5 mu, 150 mm x 2.1 mm, narrow bore column (Alltech Associates, Deerfield, IL). The method includes an isocratic run with acetonitrile-water (40:60, v/v) at 0.35 mL/min for 12 min, followed by a gradient wash with isopropyl alcohol for 20 min, to ensure that all formulation excipients are eluted. Ultraviolet detection was performed at 210 nm with a retention time for perillyl alcohol of 7 min. The high sensitivity assay utilizes a small (5 microL) injection volume for the accurate and precise analysis of perillyl alcohol from a complex cream formulation.
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10.1016/j.jpba.2004.02.039
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pubmed_72_8915
|
Previous studies from this group have shown that limit size lipid-based systems--defined as the smallest achievable aggregates compatible with the packing properties of their molecular constituents--can be efficiently produced using rapid microfluidic mixing technique. In this work, it is shown that similar procedures can be employed for the production of homogeneously sized unilamellar vesicular systems of 30-40 nm size range. These vesicles can be remotely loaded with the protonable drug doxorubicin and exhibit adequate drug retention properties in vitro and in vivo. In particular, it is demonstrated that whereas sub-40 nm lipid nanoparticle (LNP) systems consisting entirely of long-chain saturated phosphatidylcholines cannot be produced, the presence of such lipids may have a beneficial effect on the retention properties of limit size systems consisting of mixed lipid components. Specifically, a 33-nm diameter doxorubicin-loaded LNP system composed of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC), 1,2-dipalmitoyl phosphatidylcholine (DPPC), cholesterol, and PEGylated lipid (DSPE-PEG2000) demonstrated adequate, stable drug retention in the circulation, with a half-life for drug release of ∼ 12 h. These results indicate that microfluidic mixing is the technique of choice for the production of bilayer LNP systems with sizes less than 50 nm that could lead to development of a novel class of ultra-small drug delivery vehicles.
|
10.3109/08982104.2015.1025411
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pubmed_568_3093
|
Protein kinases regulate nearly all aspects of cell life, and alterations in their expression, or mutations in their genes, cause cancer and other diseases. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein and lipid kinases, resulting in the approval of more than 70 new drugs since imatinib was approved in 2001. These compounds have had a significant impact on the way in which we now treat cancers and non-cancerous conditions. We discuss how the challenge of drug resistance to kinase inhibitors is being met and the future of kinase drug discovery.
|
10.1038/s41573-021-00195-4
|
pubmed_540_5420
|
Accreditation in pathology and neuropathology in Germany is based on the requirements of the DIN EN ISO/IEC 17020 standard, which defines general requirements for the bodies performing inspections. In Germany, the national accreditation body of the Federal Republic of Germany (DAkkS) assumes the official task of accreditation. Evaluation in this area is based on a comprehensive assessment by board-certified pathologists (inspection) and is focused on correct diagnosis. The requirement of the DIN EN ISO 15189 standard on quality and competence in medical laboratories is taken into account. In Germany, more than 100 institutes of pathology and neuropathology have successfully performed the accreditation process. Interest in accreditation has been significantly growing in recent months, especially due to changes in the European law with the "Verordnung EO 2017/746 des Europäischen Parlaments und des Rates vom 05. April 2017 über Invitro-Diagnostica".However, accreditation is a demanding process that requires very good preparation. Necessary resources for accreditation should be secured before starting the process. Important framework conditions and requirements, but also some challenges that can arise during the accreditation process, are summarized in this article.
|
10.1007/s00292-022-01097-x
|
pubmed_135_5971
|
Wild birds may be healthy carriers, and therefore, may be involved in the dissemination of clinically relevant antimicrobial-resistant bacteria, such as extended-spectrum β-lactamases (ESBL) and carbapenemase-producing Enterobacteriaceae. This study evaluated whether urban pigeons living in five spots in Lisbon, Portugal, may be colonized and, therefore, constitute potential spreaders of multidrug-resistant bacteria. A total of 100 pigeon fecal samples were collected in different urban areas for the detection of ESBL- or carbapenemase-producing Enterobacteriaceae. All β-lactamase-producing isolates were tested for antimicrobial susceptibility and their genetic backgrounds were characterized by multilocus sequence typing. Of the 100 fecal samples collected, nine ESBL-producing Escherichia coli (9%) were identified. Three isolates carried the blaCTX-M-15 gene, three isolates harbored the blaCTX-M-27 and three isolates carried the blaSHV-12 gene. Genotyping of the nine ESBL-producing E. coli strains revealed seven different sequence types (STs) including ST10, ST131, ST154, ST206, ST1488 (SLV ST10), ST2858 and ST3576, most of which have been already described in humans, animals or in the environment. Urban pigeons constitute a potential source of ESBL genes and may be a transmission vehicle of multidrug-resistant bacteria in the environment.
|
10.3390/antibiotics11101368
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pubmed_812_1972
|
The postweaning development of caecal microbial activity was studied in the rabbit according to the sanitary status (conventional "C" vs. specified pathogen-free "SPF") and the nutritional status (standard-fibre "SF" vs. deficient-fibre "DF" diet). The two diets were distributed ad libitum from weaning (28 days) to 70 days of age, respectively, to 80 C and 72 SPF rabbits. From 28 to 42 days, the volatile fatty acids concentration in the caecum (tVFA) of C rabbits was 50 mM/L and increased by 46% between 42 and 56 days, without interactions with the diet effect. In parallel, the bacterial fibrolytic activity decreased for xylanase and CMCase (-32% and -60%, respectively, P<0.05), while pectinase activity decreased more regularly from 28 to 70 days (-28%, P<0.05). At weaning, tVFA was similar among C or SPF rabbits, while at 70 days, it decreased by 23% for SPF and increased in C group (+31%). Cellulasic and hemicellulasic activity of bacteria were two to three times lower, respectively, in SPF rabbits compared to conventional ones. No interaction was detected between sanitary and nutritional status at 70 days of age for the caecal fermentative activity. With the FD diet, tVFA decreased by 10%, while butyrate proportion increased by 37% (at 70 days), whatever the sanitary status. In 70-day-old rabbits (C or SPF group), pectinasic activity was reduced by 30% when rabbits were fed the FD compared to the SF one.
|
10.1016/j.cbpb.2004.09.022
|
pubmed_374_16697
|
This paper aims to perform a theoretical reflection on the historical-social foundations of the COVID-19 pandemic. The "capital worldization", "capital-imperialism", "space-time compression", and "structural crisis of capital" categories are conjured from the historical materialistic-theoretical matrix, outlining a course that transcends the limits of Health Sciences to understand global health, of which the COVID-19 pandemic is an expression. We then return to the field of health, when the category of "social determination of health" allows elucidating the bases of the pandemic studied. We show that, other elements typical of the current phase of contemporary capitalism have become universal besides the SARS-CoV-2 characteristics or the dynamics of the rapid movement of people and objects around the world, unifying the health social determination process.
|
10.1590/1413-81232020256.1.11532020
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pubmed_798_3068
|
Human beings must adapt both to novel, unfavourable conditions and to circumstances of physical or psychological isolation. The initial response to stress depends fundamentally on the activation of the HPA axis. In regaining homeostatic equilibrium, melatonin plays a role due to its synchronising and anti-stress properties. To study the role of melatonin and the pineal gland in the organic and/or behavioural response to acute or chronic stress, 311 children were divided into two large groups: 1) Control Group - 121 healthy children classified, in turn, into 4 control subgroups, one for each pathology being studied; 2) Problem Groups, classified as traumatic stress (n=58), surgical stress (n=38), psychic stress (n=64) and febrile stress (n=30), according to pre-established clinical criteria. These groups were sub-classified according to the degree (low or high) and duration (acute or chronic) of the stress. This study used a case controlled, cross sectional design. Serum melatonin was measured by radioimmunoassay (RIA). In all the situations of acute stress, melatonin increased at a rate directly proportional to the severity and/or duration of the stress-causing stimulus. In contrast, in chronic stress, i.e. the Affective Deprivation Syndrome (or Psychological Dwarfism) with or without non-organic failure to thrive, resulted in the opposite response with a significant reduction of melatonin. In conclusion, in acute stress an increase in the bioavailability of melatonin could contribute to maintaining homeostatic balance. The lack of an appropriate response to acute stress could make some groups of patients (Affective deprivation syndrome with or without growth failure) predisposed to suffer depressive symptoms associated with a wide range of neurological, endocrinological or immunological consequences.
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pubmed_798_3068
|
pubmed_4_2912
|
BACKGROUND AND PURPOSE
With the use of antibiotic therapy, the incidence of deep neck infections has decreased in recent decades. The aim of this investigation was to review the clinical course and the management of deep neck infections in our department, compare them to the experiences of the common literature and identify predisposing factors for lethal complications.
MATERIAL AND METHODS
In this single-center analysis, 63 patients with deep neck infections were treated surgically. The following clinical data were analyzed and compared: age, gender, laboratory data, spatial manifestation, therapeutic modalities, comorbidities, length of hospitalization and complications.
RESULTS
There was a predominance of male patients (58.7%) and a mean age of 57.9 years. The most common symptoms at diagnosis were sore throat (96.8%) and neck swelling (92.0%). Cardio/pulmonary diseases and diabetes mellitus were the most common comorbidities. There was a significantly longer hospital stay for patients with diabetes mellitus. The most common manifestation was a parapharyngeal abscess in 24 patients (38.1%), followed by peri-/retrotonsillar infections in 19 patients (30.2%). In 29 patients, a multiple space infection was observed, with a significantly longer duration of hospitalization and a higher rate of complications. The main life-threatening complication was the development of airway obstruction in 20 patients (31.7%), who all received a tracheostomy. The duration of hospitalization for patients with complications was significantly longer.
CONCLUSION
Close attention must be paid to the management of patients with deep neck infections, especially patients with diabetes mellitus and cardio/pulmonary diseases or patients with multiple space infections.
|
10.4317/medoral.21799
|
pubmed_156_6896
|
The nuclear factor of activated T cells (NFAT) is a calcium-dependent transcription factor that cooperates with a myriad of partner transcription factors to regulate distinct transcription programs. Transcription activation by NFAT without the cooperation of co-stimulatory signals in lymphocytes can also impose a genetic program of anergy. Although the ternary NFAT1/Fos-Jun/DNA complex has been structurally characterized, how NFAT1 recognizes DNA in the absence of cooperative partners and how such a binary NFAT/DNA complex may lead to the assembly of distinct high-order NFAT transcription complexes are still poorly understood. We have determined the crystal structure of the entire Rel homology region (RHR) of human NFAT1 (NFATc2) bound to DNA as a monomer. We also present footprinting evidence that corroborates the protein-DNA contacts observed in the crystal structure. Our structural and biochemical studies reveal the mechanism by which the monomeric Rel protein NFAT recognizes its cognate DNA site. A remarkable feature of the binary NFAT/DNA complex is the conformational flexibility exhibited by NFAT1 in the four independent copies of the NFAT/DNA complex in the crystal structure, which may reflect a mechanism by which NFAT1 interacts with a variety of protein partners as it mediates disparate biological responses.
|
10.1016/j.jmb.2003.09.065
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pubmed_603_16778
|
In this study, an ionic liquid-based microwave-assisted extraction (ILMAE) followed by high-performance liquid chromatography-diode array detector with a pentafluorophenyl column for the extraction and quantification of eight flavonoid glycosides in pigeon pea leaves is described. Compared with conventional extraction methods, ILMAE is a more effective and environment friendly method for the extraction of nature compounds from herbal plants. Nine different types of ionic liquids with different cations and anions were investigated. The results suggested that varying the anion and cation had significant effects on the extraction of flavonoid glycosides, and 1.0 M 1-butyl-3-methylimidazolium bromide ([C4MIM]Br) solution was selected as solvent. In addition, the extraction procedures were also optimized using a series of single-factor experiments. The optimum parameters were obtained as follows: extraction temperature 60°C, liquid-solid ratio 20:1 mL/g and extraction time 13 min. Moreover, an HPLC method using pentafluorophenyl column was established and validated. Good linearity was observed with the regression coefficients (r(2)) more than 0.999. The limit of detection (LODs) (S/N = 3) and limit of quantification (LOQs) (S/N = 10) for the components were less than 0.41 and 1.47 μg/mL, respectively. The inter- and intraday precisions that were used to evaluate the reproducibility and relative standard deviation (RSD) values were less than 4.57%. The recoveries were between 97.26 and 102.69%. The method was successfully used for the analysis of samples of pigeon pea leaves. In conclusion, the developed ILMAE-HPLC-diode array detector using pentafluorophenyl column method can be applied for quality control of pigeon pea leaves and related medicinal products.
|
10.1002/jssc.201200473
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pubmed_78_12581
|
The mature penaeid oocytes possess cortical rods that contain two related cortical rod proteins (CRP, 28.6 kDa and 30.5 kDa). In the present study, localization of CRP mRNA and gene expression profiles of CRP and vitellogenin (Vg) during ovarian development were examined in kuruma prawn, Marsupenaeus japonicus, an economically important species for shrimp and prawn farming. Northern blot analysis revealed that CRP mRNA was expressed in the ovary. In situ hybridization showed strong signals for CRP transcripts in the oocytes at early developmental stages in both immature and mature ovaries. Quantitative analysis by real-time polymerase chain reaction revealed that CRP mRNA levels were higher in the previtellogenic and endogenous (primary) vitellogenic stages than in more advanced stages. Unlike CRP mRNA, Vg mRNA levels were low in the ovary and hepatopancreas in previtellogenic females. When the ovary developed into the endogenous vitellogenic stage, ovarian Vg mRNA levels increased significantly, followed by rapid decrease in more advanced stages. The Vg mRNA levels in the hepatopancreas, on the other hand, tended to be high in the exogenous (secondary) vitellogenic and maturation stages, in which ovarian Vg mRNA levels were decreased. Our findings indicate that CRP mRNA is highly expressed before the onset of vitellogenesis, suggesting that the transcription, translation, and cortical-rod formation of CRP occur at different phases of oocyte development. The endogenous vitellogenic stage is a crucial stage for the initiation of CRP and Vg syntheses. The coincidence of these protein syntheses suggests that CRP and Vg syntheses are regulated by closely-related mechanisms.
|
10.2108/zsj.22.675
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pubmed_302_7839
|
Drebrin A, a major neuronal actin-binding protein, regulates the dendritic spine shapes of neurons. Here, we have cloned and characterized a novel mouse cDNA clone encoding a truncated form of drebrin A, named s-drebrin A. Analysis of the genomic organization of the mouse drebrin gene (Dbn1), which mapped to the central portion of chromosome 13, revealed that isoforms including s-drebrin A are generated by alternative splicing from a single drebrin gene. The s-drebrin A mRNA was expressed in the brain, but not in non-neuronal tissues. The s-drebrin A expression was barely detected in the embryonic brain, but was upregulated during postnatal development of the brain. Overexpression of GFP-tagged s-drebrin A in fibroblasts showed it to be associated with actin filaments and with changes in actin cytoskeleton organization. These findings suggest that s-drebrin A has a role in spine morphogenesis, possibly by competing the actin-binding activity with drebrin A.
|
10.1006/geno.2002.6764
|
pubmed_78_12202
|
We have previously demonstrated that bcl-2 overexpression in tumor cells exposed to hypoxia increases the expression of vascular endothelial growth factor (VEGF) gene through the hypoxia-inducible factor-1 (HIF-1). In this article, we demonstrate that exposure of bcl-2 overexpressing melanoma cells to hypoxia induced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2 proteins. On the contrary, no modulation of these pathways by bcl-2 was observed under normoxic conditions. When HIF-1alpha expression was reduced by RNA interference, AKT and ERK1/2 phosphorylation were still induced by bcl-2. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia. No differences were observed between control and bcl-2-overexpressing cells in normoxia, in terms of VEGF protein secretion and in response to PI3K and MAPK inhibitors. We also demonstrated that RNA interference-mediated down-regulation of bcl-2 expression resulted in a decrease in the ERK1/2 phosphorylation and VEGF secretion only in bcl-2-overexpressing cell exposed to hypoxia but not in control cells. In conclusion, our results indicate, for the first time, that bcl-2 synergizes with hypoxia to promote expression of angiogenesis factors in melanoma cells through both PI3K- and MAPK-dependent pathways.
|
10.1091/mbc.e04-12-1087
|
pubmed_418_8697
|
RATIONALE AND OBJECTIVES
To determine the accuracy of semiautomated CT volumetry using portal vein (PV) segmentation to estimate volume of the right posterior section (RPS) graft compared to intraoperative measured weight (W) in live liver donors.
MATERIALS AND METHODS
Among 23 donors who donated RPS grafts for liver transplantation in our institution from April 2003 to August 2016, 17 donors with CT scans within 3 months of liver procurement and PV anatomy of type I-III were included. RPS volumes were retrospectively evaluated by semiautomated CT volumetry (RPSVCTV) and by measurement of standard liver volume (SLV) and PV area ratio (RPSVSLV). RPS volumes were compared to W for correlation coefficients, (absolute) difference, and (absolute) percentage deviation. Linear fitting was performed to identify the method that yielded the greatest correlation with W.
RESULTS
Mean values of RPSVCTV, RPSVSLV, and W were 503.4 ± 97.8 mL (346.6-686.0), 516.54 ± 146.20 (274.06-776.32), and 518.8 ± 122.4 (370.0-789.0), respectively. RPSVCTV was strongly correlated with W (r = 0.9414; p < 0.0001), whereas RPSVSLV was only moderately did (r = 0.5899; p = 0.0127). RPSVCTV showed a significantly smaller absolute difference (35.20 ± 30.82 vs. 104.79 ± 60.27, p = 0.004) and absolute percentage deviation (6.61 ± 4.90 vs. 19.92 ± 10.37, p < 0.0001) from W. Equation correlating RPSVCTV and W was W = -74.7191 + 1.1791 RPSVCTV (R2 = 0.8862; p < 0.001).
CONCLUSION
RPSVCTV yields smaller absolute difference than RPSVSLV for estimating intraoperative measured weight of RPS in live liver donors. Semiautomated CT volumetry using PV segmentation is feasible for the estimation of the volume of the RPS of the liver, and RPSVCTV was strongly correlated with W (r = 0.9414; p < 0.0001).
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10.1016/j.acra.2019.03.018
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pubmed_825_7193
|
This analysis compares nursing home costs, Medicaid payment rates, and profits under three Medicaid nursing home payment systems: case-mix, facility-specific, and class-rate systems. Data used were collected from 135 nursing homes in seven states. The association of case mix with costs, rates, and profits under the three payment systems was of particular interest. Case mix was more strongly associated (positively) with patient care cost and the Medicaid rate for the case-mix systems than for the other systems, particularly the class-rate systems. In contrast, case mix and profits were not associated in the case-mix or facility-specific systems, but were negatively associated in the class rate systems. Overall, the results suggest that case-mix systems have some important advantages over other payment systems, but further research is needed on larger samples and involving the newer case-mix systems.
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pubmed_825_7193
|
pubmed_812_22321
|
The elicitation of broadly neutralizing antibodies directed against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, gp120 and gp41, remains a major challenge. Attempts to utilize monomeric gp120 as an immunogen to elicit high titers of neutralizing antibodies have been disappointing. Envelope glycoprotein constructs that better reflect the trimeric structure of the functional envelope spike have exhibited improved immunogenicity compared with monomeric gp120. We have described soluble gp140 ectodomain constructs with a heterologous trimerization motif; these have previously been shown to elicit antibodies in mice that were able to neutralize a number of HIV-1 isolates, among them primary isolate viruses. Recently, solid-phase proteoliposomes retaining the envelope glycoproteins as trimeric spikes in a physiologic membrane setting have been described. Here, we compare the immunogenic properties of these two trimeric envelope glycoprotein formulations and monomeric gp120 in rabbits. Both trimeric envelope glycoprotein preparations generated neutralizing antibodies more effectively than gp120. In contrast to monomeric gp120, the trimeric envelope glycoproteins elicited neutralizing antibodies with some breadth of neutralization. Furthermore, repeated boosting with the soluble trimeric formulations resulted in an increase in potency that allowed neutralization of a subset of neutralization-resistant HIV-1 primary isolates. We demonstrate that the neutralization is concentration-dependent, is mediated by serum IgG and that the major portion of the neutralizing activity is not directed against the gp120 V3 loop. Thus, mimics of the trimeric envelope glycoprotein spike described here elicit HIV-1-neutralizing antibodies that could contribute to a protective immune response and provide platforms for further modifications to improve the efficiency of this process.
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10.1016/j.virol.2004.09.022
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pubmed_762_13440
|
Four sourdoughs (A to D) were produced under practical conditions by using a starter mixture of three commercially available sourdough starters and a baker's yeast constitutively containing various species of lactic acid bacteria (LAB). The sourdoughs were continuously propagated until the composition of the LAB flora remained stable. Two LAB-specific PCR-denaturing gradient gel electrophoresis (DGGE) systems were established and used to monitor the development of the microflora. Depending on the prevailing ecological conditions in the different sourdough fermentations, only a few Lactobacillus species were found to be competitive and became dominant. In sourdough A (traditional process with rye flour), Lactobacillus sanfranciscensis and a new species, L. mindensis, were detected. In rye flour sourdoughs B and C, which differed in the process temperature, exclusively L. crispatus and L. pontis became the predominant species in sourdough B and L. crispatus, L. panis, and L. frumenti became the predominant species in sourdough C. On the other hand, in sourdough D (corresponding to sourdough C but produced with rye bran), L. johnsonii and L. reuteri were found. The results of PCR-DGGE were consistent with those obtained by culturing, except for sourdough B, in which L. fermentum was also detected. Isolates of the species L. sanfranciscensis and L. fermentum were shown by randomly amplified polymorphic DNA-PCR analysis to originate from the commercial starters and the baker's yeast, respectively.
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10.1128/AEM.69.1.475-482.2003
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pubmed_268_3065
|
The iris and the skin of the lateral canthus of patients with exfoliation syndrome were studied by light and electron microscopy. The materials were surgically obtained from 9 patients of cataract and/or glaucoma associated with exfoliation syndrome. For the control study, we prepared the iris and the skin of 6 patients without exfoliation syndrome. In all 9 cases of exfoliation syndrome, exfoliative materials were observed in the pigment epithelium of the iris. In 3 of 9 cases, exfoliative materials were found in the dermis. In 6 other cases, microfibrils and immature forms of exfoliative materials were observed, but not typical forms. Neither in the iris nor in the skin of the control cases were exfoliative materials detected. Exfoliative materials in the dermis seen in the patients with exfoliation syndrome were morphologically similar to those in the iris. This is the first report of demonstration of exfoliative materials in the skin. These observations suggest that exfoliation syndrome may be a systemic degenerative disorder of the body.
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pubmed_268_3065
|
pubmed_92_11096
|
PURPOSE
The aim of this study is to evaluate the efficacy and safety of interventional radiology procedures in the treatment of major urological complications after kidney transplantation.
MATERIALS AND METHODS
Between 2000 and 2010, 1,146 kidney transplants were performed at our institution. A total of 146 major complications occurred, including 77 obstructions, 36 leaks and 33 associated perigraft fluid collections. Percutaneous treatment was carried out in 118/146 complications in 91 patients. In the case of stenosis-obstruction and fistulas (104 complications), the first therapeutic step was placement of a nephrostomy catheter, followed by balloon ureteroplasty, placement of external-internal catheters and double-J stents; 14/33 collections were drained under ultrasound guidance.
RESULTS
In all 118 percutaneous interventions, we were able to place a nephrostomy or drainage catheter, with a technical success rate of 100 %. The long-term success rate was 49.6 %: in 57/115 (three patients were lost to follow-up) we obtained the complete resolution of the complication. The procedure-related mortality rate was 0 %. There was only one major complication and the rate of minor complications was 14.4 %.
CONCLUSIONS
Interventional radiology is the first choice option in the treatment of urological complications after kidney transplantation.
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10.1007/s11547-014-0407-y
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pubmed_307_21937
|
Traumatic brain injury (TBI) is a major public health issue affecting 1.7 million Americans each year, of which approximately 50,000 are fatal. High-fat sucrose (HFS) diets are another public health issue which can lead to obesity, hypertension, and many other debilitating disorders. These two disorders combined can lead to more complicated issues. It has recently been shown that HFS diets can reduce levels of brain-derived neurotrophic factor (BDNF) leading to reductions in neuronal and behavioral plasticity. This reduction in BDNF is suspected of increasing the susceptibility of the brain to injury. To test the effects of a HFS diet on recovery of function post-TBI, male Sprague-Dawley rats were used in this study. Eight weeks prior to TBI, rats were placed on a special HFS diet (n=14) or a standard rodent diet (n=14). Following this eight-week period, rats were prepared with bilateral frontal cortical contusion injuries (CCI) or sham procedures. Beginning two days post-TBI, animals were tested on a battery of behavioral tests to assess somatosensory dysfunction and spatial memory in the Morris water maze, with a reference memory and a working memory task. Following testing, animals were sacrificed and their brains processed for lesion analysis. The HFS diet worsened performance on the bilateral tactile adhesive removal test in sham animals. Injured animals on the Standard diet had a greater improvement in somatosensory performance in the adhesive removal test and had better performance on the working memory task compared to animals on the HFS diet. The HFS diet also resulted in significantly greater loss of cortical tissue post-CCI than in the Standard diet group. This study may aid in determining how nutritional characteristics or habits interact with damage to the brain.
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10.1016/j.bbr.2011.04.028
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pubmed_894_7933
|
The authors have used Moxalactam as single antibiotic therapy in a series of 20 patients with primary or secondary peritonitis in order to test its efficiency on aerobic and anaerobic bacteria. Four early deaths and one late death not directly related to the peritoneal infectious process were recorded. In 95% of cases, the peritoneal infection was controlled by the association of Moxalactam and adequate surgery.
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pubmed_894_7933
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pubmed_457_5910
|
ELIXIR is the European infrastructure established specifically for the sharing and sustainability of life science data. To provide up-to-date resources and services, ELIXIR needs to undergo a continuous process of refreshing the services provided by its national Nodes. Here we present the approach taken by ELIXIR-UK to address the advice by the ELIXIR Scientific Advisory Board that Nodes need to develop " mechanisms to ensure that each Node continues to be representative of the Bioinformatics efforts within the country". ELIXIR-UK put in place an open and transparent process to identify potential ELIXIR resources within the UK during late 2015 and early to mid-2016. Areas of strategic strength were identified and Expressions of Interest in these priority areas were requested from the UK community. A set of criteria were established, in discussion with the ELIXIR Hub, and prospective ELIXIR-UK resources were assessed by an independent committee set up by the Node for this purpose. Of 19 resources considered, 14 were judged to be immediately ready to be included in the UK ELIXIR Node's portfolio. A further five were placed on the Node's roadmap for future consideration for inclusion. ELIXIR-UK expects to repeat this process regularly to ensure its portfolio continues to reflect its community's strengths.
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10.12688/f1000research.10473.1
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pubmed_286_1740
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AIM
This study aimed to investigate the incidence, timing, manifestations, managements, and outcomes of Epstein-Barr virus (EBV) infection in paediatric renal transplant recipients in Korea.
METHODS
We retrospectively evaluated 70 patients aged <18 years who had undergone renal transplantation between January 1990 and November 2014 at a single centre in Korea. EBV infection was diagnosed via serological test or real-time quantitative polymerase chain reaction (PCR). The diagnosis of post-transplant lymphoproliferative disorder (PTLD) was based on biopsy findings.
RESULTS
In total, 21 patients (30.0% of renal transplant recipients) had EBV infection. EBV infection occurred at an average age of 12.6 ± 4.5 (median, 12.0; range, 7.0-24.0 years, with a mean period of 28.3 ± 27.2 (median, 14.0; range, 2.0-75.0) months for developing EBV infection after transplantation. EBV infection developed 12 times more frequently in pre-transplant EBV-seronegative recipients. Eight patients (38% of EBV-infected patients) had EBV disease, and six patients (75% of patients with EBV disease) had PTLD. The maximum EBV PCR titer was greater in patients with EBV disease than in the asymptomatic EBV infection group. The main treatment for EBV infection was the reduction in immunosuppressants. Asymptomatic EBV infection resolved in approximately 80% of the patients. One patient (17% of the patients with PTLD) expired. The glomerular filtration rate did not deteriorate during the treatment of EBV infection.
CONCLUSION
Regular EBV monitoring in renal transplant recipients is mandatory for early diagnosis and treatment of EBV infections and prevention of PTLD, especially in pre-transplant EBV IgG-negative patients.
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10.1111/nep.13162
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pubmed_1040_18414
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In many cases no fixed standards are available and a sample from a target population is used to provide the necessary quality-control norms. Furthermore, many products possess several correlated attributes that are relevant to the authenticity question. This article addresses some issues related to statistical tests used in such cases, focussing in particular on a procedure that has been lately proposed for differentiating between pure and adulterated fruit juice. The quality control of fruit juice is usually performed by comparing the values of several characteristics in the tested sample against some prespecified standards. In many cases those standards are based on the values found in a sample of a presumably pure juice, which is used as a "reference sample" or a "base sample". Several detection methods were recently proposed that use universal "base samples" and are supposed to be valid when applied to juices from different sources or different varieties. We compare the results yielded by the use of various "base samples" and show that the application of such a method to Israeli citrus juice leads to too many rejections of pure juices. We suggest that the main drawbacks of the method is the use of improper "base sample" that is not specific to the sample being tested.
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10.1007/BF01027771
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pubmed_465_889
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Thyroid hormones have a direct effect on the basal or resting metabolic rate in man and a permissive effect on the adaptive thermogenesis of small animals, while altering the energy expended in exercise to the extent that patients with thyroid disorders exercise to a greater or lesser degree. The physiological concepts of energy expenditure need to be seen in the context of a new method for measuring 'thyroid thermogenesis'. Thyroid hormones seem, in evolutionary terms, to have developed a thermogenic role during the transition from poikilothermy to homeothermy; they are responsible for the increased heat production required for homeotherms to maintain body temperature above that of the environment. The potential mechanisms responsible for thyroid hormone-controlled energy expenditure are complex. Uncoupled oxidative phosphorylation is probably not responsible for thyroid hormone-controlled thermogenesis except in the special case of brown adipose tissue thermogenesis, where thyroid hormones act permissively. The concept that increased ATP generation must be coupled to ATP utilization needs to be linked with the idea that thyroid hormone-controlled thermogenesis must be through inefficient pathways of metabolism. Several of these potentially important pathways of intermediary metabolism in thyroid hormone-controlled thermogenesis can now be defined and measured, but their role in the regulation of nutritionally induced alterations in thyroid status and thermogenesis remains to be explored.
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10.1016/s0300-595x(84)80039-0
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pubmed_1034_20059
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BACKGROUND
It is important that all undergraduate healthcare students are equipped with evidence-based health care (EBHC) knowledge and skills to encourage evidence-informed decision-making after graduation. We assessed EBHC teaching and learning in undergraduate human nutrition (HN); occupational therapy (OT); physiotherapy (PT); and speech, language and hearing therapy (SPLH) programs at a sub-Saharan African university.
METHODS
We used methodological triangulation to obtain a comprehensive understanding of EBHC teaching and learning: (1) through a document review of module guides, we identified learning outcomes related to pre-specified EBHC competencies; we conducted (2) focus group discussions and interviews of lecturers to obtain their perspectives on EBHC and on EBHC teaching and learning; and we (3) invited final year students (2013) and 2012 graduates to complete an online survey on EBHC attitudes, self-perceived EBHC competence, and their experience of EBHC teaching and learning.
RESULTS
We reviewed all module outlines (n = 89) from HN, PT and SLHT. The OT curriculum was being revised at that time and could not be included. Six lecturers each from HN and OT, and five lecturers each from PT and SLHT participated in the focus groups. Thirty percent (53/176) of invited students responded to the survey. EBHC competencies were addressed to varying degrees in the four programs, although EBHC teaching and learning mostly occurred implicitly. Learning outcomes referring to EBHC focused on enabling competencies (e.g., critical thinking, biostatistics, epidemiology) and were concentrated in theoretical modules. Key competencies (e.g., asking questions, searching databases, critical appraisal) were rarely addressed explicitly. Students felt that EBHC learning should be integrated throughout the four year study period to allow for repetition, consolidation and application of knowledge and skills. Lecturers highlighted several challenges to teaching and practising EBHC, including lack of evidence relevant to the African context and lack of time within curricula.
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10.1371/journal.pone.0172199
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pubmed_510_10380
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The consequences of the interaction of heat-killed bacteria and lipopolysaccharide (LPS) with a pure population of bone marrow-derived mononuclear phagocytes (BMMø) were investigated, utilizing changes in the flow of L-arginine and expression of tumoricidal activity as parameters of macrophage (mø) function. Gram negative bacteria and LPS proved potent in inducing the flow of L-arginine through the nitric oxide and the urea pathways but were mostly poor in eliciting tumoricidal activity. Gram positive bacteria affected the metabolism of L-arginine only little but were often efficient in triggering tumoricidal activity. The findings show that the mø response to bacteria, which may determine the outcome of their interaction with the host, may differ considerably depending on the type of bacteria.
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10.1016/0006-291x(91)91863-8
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pubmed_87_20729
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Hyaluronan (HA) may have proinflammatory roles in the context of CNS autoimmunity. It accumulates in demyelinated multiple sclerosis (MS) lesions, promotes antigen presentation, and enhances T-cell activation and proliferation. HA facilitates lymphocyte binding to vessels and CNS infiltration at the CNS vascular endothelium. Furthermore, HA signals through Toll-like receptors 2 and 4 to stimulate inflammatory gene expression. We assessed the role of HA in experimental autoimmune encephalomyelitis (EAE), an animal model of MS by administration of 4-methylumbelliferone (4MU), a well established inhibitor of HA synthesis. 4MU decreased hyaluronan synthesis in vitro and in vivo. It was protective in active EAE of C57Bl/6 mice, decreased spinal inflammatory infiltrates and spinal infiltration of Th1 cells, and increased differentiation of regulatory T-cells. In adoptive transfer EAE, feeding of 4MU to donor mice significantly decreased the encephalitogenicity of lymph node cells. The transfer of proteolipid protein (PLP)-stimulated lymph node cells to 4MU-fed mice resulted in a delayed EAE onset and delayed spinal T-cell infiltration. Expression of CXCL12, an anti-inflammatory chemokine, is reduced in MS patients in CSF cells and in spinal cord tissue during EAE. Hyaluronan suppressed production of CXCL12, whereas 4MU increased spinal CXCL12 in naive animals and during neuroinflammation. Neutralization of CXCR4, the most prominent receptor of CXCL12, by administration of AMD3100 diminished the protective impact of 4MU in adoptive transfer EAE. In conclusion, hyaluronan exacerbates CNS autoimmunity, enhances encephalitogenic T-cell responses, and suppresses the protective chemokine CXCL12 in CNS tissue. Inhibition of hyaluronan synthesis with 4MU protects against an animal model of MS and may represent an important therapeutic option in MS and other neuroinflammatory diseases.
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10.1074/jbc.M114.559583
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pubmed_54_8729
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PURPOSE
We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval.
METHODS AND MATERIALS
PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier.
RESULTS
The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%).
CONCLUSION
Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
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pubmed_54_8729
|
pubmed_834_11410
|
In the epidermis, one of the earliest characterized events in keratinocyte differentiation is the coordinate induction of a pair of keratins specifically expressed in suprabasal cells, keratin 1 (K1) and keratin 10 (K10). Both in vivo and in vitro, extracellular calcium is necessary for several biochemical and structural changes during keratinocyte differentiation. However, it has been unclear if calcium serves as a differentiation signal in keratinocytes. In these studies, expression of suprabasal keratin mRNA and protein is used to test whether the initial differentiation of primary mouse keratinocytes in vitro is dependent on changes in the concentration of extracellular calcium. K1 mRNA was expressed at low levels in cultures of keratinocytes growing on plastic in 0.05 mM calcium but in attached cells was not further induced by increases in the concentration of extracellular calcium. Suspension of the keratinocytes into semi-solid medium induced a rapid and substantial increase in both expression of K1 mRNA and in the percentage of cells expressing suprabasal keratin proteins. The induction was unaffected by the concentration of calcium in the semi-solid medium and could not be enhanced by exposing attached cells to higher calcium before suspension. The induction of K1 mRNA could be inhibited by exposure of the keratinocytes to either EGF or fibronectin. These results suggest that commitment of mouse keratinocytes to terminal differentiation is independent of extracellular calcium and may be regulated primarily by extracellular factors other than calcium.
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10.1083/jcb.123.4.909
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pubmed_667_5973
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In motile, eukaryotic cells, a variety of cell-associated material (collectively termed here as 'particles') continuously flows, relative to the substratum, from the front to the back of the extreme margin of the cell (termed the 'lamellipodium'). This retrograde particle flow, occurs both over the surface of, and inside the lamellipodium. Force to drive retrograde particle flow in lamellipodia is dependent on actin filaments, but the precise mechanism of force generation, and function of the flow is generally not well understood. Actin filaments themselves, in lamellipodia of most motile cell types studied also flow retrograde relative to the substratum. This actin flow, in Aplysia bag cell neuronal growth cones, is known to be driven by activity of a myosin. In these growth cones, retrograde flow of cell surface-attached particles is coupled to retrograde actin flow. In Aplysia, force from retrograde actin flow may limit certain types of growth cone motility. In other motile cell types, such as keratocytes and fibroblasts, the mechanism of retrograde particle flow and function of retrograde actin flow in lamellipodia is poorly understood. For these cell types, recent data provide a basis for proposing alternative actin-based mechanisms to drive retrograde particle flow in lamellipodia. One mechanism is based on activity of a putative pointed end- directed actin motor, and the other on tension-driven surface lipid flow. Here I will review recent advances that have been made in determining the molecular mechanism of force generation to drive retrograde particle flow relative to the substratum in lamellipodia of motile cells. I will address the function of retrograde actin flow in lamellipodia, and apparent differences between Aplysia and other motile cell types.
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10.2741/a189
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pubmed_275_1364
|
BACKGROUND
Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown.
METHODS AND RESULTS
In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P<0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P=0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P<0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (P=0.01) and in ischemic TVR from 20.4% to 10.8% (P=0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates.
CONCLUSIONS
The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.
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10.1161/01.CIR.0000160362.55803.40
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pubmed_29_569
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In a 10-year follow-up study of 543 men and 180 women seen in a community survey in 1958 mortality was examined in relation to the 1958 haematological data, and 91% of the survivors were re-examined. Analyses based on the 1958 haemoglobin and packed cell volume estimations suggested that those with values near the mean may subsequently have lower death rates. Higher death rates occurred in those having low serum iron levels. Comparisons of haemoglobin concentrations and of packed cell volumes in 1958 and 1968 show correlation coefficients (r) between 0.30 and 0.60 in various subgroups.
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10.1136/bmj.4.5686.761
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pubmed_1084_22315
|
BACKGROUND
Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features.
METHODS
In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons.
RESULTS
A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA).
CONCLUSIONS
Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.
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10.1186/1471-2377-11-134
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pubmed_703_1355
|
Targeting DNA repair with poly(ADP-ribose) polymerase (PARP) inhibitors has shown a broad range of anti-tumor activity in patients with advanced malignancies with and without BRCA deficiency. It remains unclear what role p53 plays in response to PARP inhibition in BRCA-proficient cancer cells treated with DNA damaging agents. Using gene expression microarray analysis, we find that DNA damage response (DDR) pathways elicited by veliparib (ABT-888), a PARP inhibitor, plus topotecan comprise the G1/S checkpoint, ATM, and p53 signaling pathways in p53-wildtype cancer cell lines and BRCA1, BRCA2 and ATR pathway in p53-mutant lines. In contrast, topotecan alone induces the G1/S checkpoint pathway in p53-wildtype lines and not in p53-mutant cells. These responses are coupled with G2/G1 checkpoint effectors p21(CDKN1A) upregulation, and Chk1 and Chk2 activation. The drug combination enhances G2 cell cycle arrest, apoptosis and a marked increase in cell death relative to topotecan alone in p53-wildtype and p53-mutant or -null cells. We also show that the checkpoint kinase inhibitor UCN-01 abolishes the G2 arrest induced by the veliparib and topotecan combination and further increases cell death in both p53-wildtype and -mutant cells. Collectively, PARP inhibition by veliparib enhances DDR and cell death in BRCA-proficient cancer cells in a p53-dependent and -independent fashion. Abrogating the cell-cycle arrest induced by PARP inhibition plus chemotherapeutics may be a strategy in the treatment of BRCA-proficient cancer.
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10.4161/cc.10.23.18170
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pubmed_44_6084
|
PURPOSE
To test the usefulness of diagnostic peritoneal lavage (DPL) for identifying blunt hollow visceral injury with two different sets of criteria or a combination of the two.
METHODS
Fifty victims with physical examinations and/or computed tomography findings equivocal for blunt hollow visceral injury underwent DPL. Whether or not to perform surgery was determined based on Otomo's DPL criteria [lavage white blood cell counts (L-WBC) over lavage red blood cell counts (L-RBC) divided by 150 (L-WBC > or = L-RBC/150) in the presence of hemoperitoneum, or L-WBC over 500/mm(3) (L-WBC > or = 500) in the absence of hemoperitoneum]. The cell count ratio, a comparison of L-WBC, L-RBC, peripheral WBC (P-WBC), and peripheral RBC (P-RBC) [(L-WBC/L-RBC)/(P-WBC/P-RBC) > or = 1] were all calculated retrospectively.
RESULTS
There were one and two false-positive cases based on Otomo's criteria and the cell count ratio, respectively, with corresponding accuracies of 97.8% and 95.7%, respectively. There were no false-positive or -negative cases according to the combined use of Otomo's criteria and cell count ratio, yielding an accuracy of 100%.
CONCLUSION
Although each criterion alone is very accurate in predicting the presence of blunt hollow visceral injury, the combined use of the two would further improve the accuracy of the diagnosis and thereby reduce the number of unnecessary celiotomies.
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10.1007/s00595-005-3065-9
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pubmed_1092_15703
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The role of spatial arrangements on the spread and management strategies of a cholera epidemic is investigated. We consider the effect of human and pathogen movement on optimal vaccination strategies. A metapopulation model is used, incorporating a susceptible-infected-recovered system of differential equations coupled with an equation modelling the concentration of Vibrio cholerae in an aquatic reservoir. The model compared spatial arrangements and varying scenarios to draw conclusions on how to effectively manage outbreaks. The work is motivated by the 2010 cholera outbreak in Haiti. Results give guidance for vaccination strategies in response to an outbreak.
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10.1080/17513758.2016.1156172
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pubmed_680_4416
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Sleep has strong influences on affective and social experiences. However, less is known about the reciprocal effects of sleep, affect, and social experiences at a daily level, and little work has considered racial/ethnic minorities at high risk for social disconnection and discrimination. A 7-day daily experience study assessed the bidirectional relationships between daily sleep quality, affect, social experiences, and overall well-being among a sample of Latinx undergraduates (N = 109). Each morning, participants reported on their previous night's sleep. Each evening, they reported their positive and negative affect, experiences of belonging and unfair treatment, and overall well-being that day. Results indicate that, at a daily level, sleep quality predicts next-day affect, belonging, and well-being. Reciprocally, only daily well-being predicts sleep quality. Findings highlight sleep as a potentially powerful antecedent of affective and social experiences likely to be particularly potent for underrepresented minority groups.
Supplementary Information
The online version contains supplementary material available at 10.1007/s42761-021-00088-0.
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10.1007/s42761-021-00088-0
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pubmed_949_7683
|
The aim of this study was to assess the feasibility and effectiveness of intrapleural administration of recombinant human interleukin-2 (rhIL-2) for treatment of malignant pleural effusions. From May 1993 to May 1995, 21 patients with non-small cell lung cancer (NSCLC) and cytologically documented malignant pleural effusion entered the study. After complete needle drainage of the effusion, a dose of 9 x 10(6) international units (IU) rhIL-2 was injected intracavitarily. The drug was injected on the first and second day each week for 3 weeks, in relation to the presence of effusion. Complete response (according to the criteria reported by Paladine st al.) was achieved in 7 of the 21 patients (33%), and partial response in 6 of the 21 patients (29%), with a median duration of 8 months (range 4-10 months). The treatment was well tolerated by all patients. Intracavitary administration of low-dose recombinant human interleukin-2 in malignant pleural effusion due to non-small cell lung cancer is an effective and well tolerated therapeutic strategy.
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pubmed_949_7683
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pubmed_505_21493
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Thermodynamic differences between ibuprofen (IBP) racemate and the (+)-enantiomer were studied by X-ray diffraction, thermoanalysis, and crystal energy calculations. The thermodynamic functions of sublimation (as a measure of crystal lattice energy) were obtained by the transpiration method. The sublimation enthalpies (DeltaH(sub)) of (+/-)-IBP and (+)-IBP are 115.8 +/- 0.6 and 107.4 +/- 0.5 kJ. mol(-1), respectively. Using the temperature dependency of the saturated vapor pressure, the relative fractions of enthalpy and entropy of the sublimation process were calculated, and the sublimation process for both the racemate and the enantiomer was found to be enthalpy driven (62%). Two different force fields, Mayo et al. (M) and Gavezzotti (G), were used for comparative analysis of crystal lattice energies. Both force fields revealed that the van der Waals term contributes more to the packing energy in (+)-IBP than in (+/-)-IBP. The hydrogen bonding energy, however, contributes at 29.7 and 32.3% to the total crystal lattice energy in (+)-IBP and (+/-)-IBP (M), respectively. Furthermore, different structure fragments of the IBP molecule were analyzed with respect to their contribution to nonbonded van der Waals interactions. The effect of the C-H distance on the van der Waals term of the crystal lattice energy was also studied.
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10.1002/jps.10586
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pubmed_974_5821
|
Recently, preparation of mesoporous fibers has attracted extensive attentions because of their unique and broad applications in photocatalysis, optoelectronics, and biomaterials. However, it remains a great challenge to fabricate thoroughly mesoporous nanofibers with high purity and uniformity. Here, we report a general, simple and cost-effective strategy, namely, foaming-assisted electrospinning, for producing mesoporous nanofibers with high purity and enhanced specific surface areas. As a proof of concept, the as-fabricated mesoporous TiO2 fibers exhibit much higher photocatalytic activity and stability than both the conventional solid counterparts and the commercially available P25. The abundant vapors released from the introduced foaming agents are responsible for the creation of pores with uniform spatial distribution in the spun precursor fibers. The present work represents a critically important step in advancing the electrospinning technique for generating mesoporous fibers in a facile and universal manner.
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10.1021/ja508840c
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pubmed_52_79
|
Reproduction is essential to all organisms if they are to contribute to the next generation. There are various means and ways of achieving this goal. This review focuses on the role of asexual reproduction for eukaryotic organisms and how its integration in a life cycle can influence their population genetics and evolution. An important question for evolutionary biologists as to why some organisms reproduce sexually, as opposed to asexually, is addressed. We also discuss the economic and medical importance of asexual organisms.
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10.1007/s00018-007-6515-2
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pubmed_1021_13425
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Ten consecutive eyes that had undergone a pars plana vitrectomy and argon endolaser photocoagulation for penetrating or perforating posterior segment foreign bodies were reviewed. All eyes had undergone a pars plana vitrectomy plus or minus lensectomy, removal of the intraocular foreign body in those eyes with a retained foreign body, endolaser photocoagulation of posterior chorioretinal tears, and peripheral buckle for peripheral retinal pathology. Postoperatively (minimum follow-up, 6 months), all eyes had an attached retina. Eighty percent of the eyes had a visual acuity of 20/40 or better. Advantages of endolaser photocoagulation of posterior breaks include: microscopically controlled sealing of posterior tears, less destructive than posterior cryotherapy, effective when severe choroidal swelling is present, and absence of dispersion of viable retinal pigment epithelial cells which has been documented with external cryotherapy.
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10.1177/112067219100100303
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pubmed_613_25210
|
BACKGROUND
A major portion of influenza disease burden during the 2009 pandemic was observed among young people.
METHODS
We examined the effect of age on the transmission of influenza-like illness associated with the 2009 pandemic influenza A (H1N1) virus (pH1N1) for an April-May 2009 outbreak among youth-camp participants and household contacts in Washington State.
RESULTS
An influenza-like illness attack rate of 51% was found among 96 camp participants. We observed a cabin secondary attack rate of 42% (95% confidence interval = 21%-66%) and a camp local reproductive number of 2.7 (1.7-4.1) for influenza-like illness among children (less than 18 years old). Among the 136 contacts in the 41 households with an influenza-like illness index case who attended the camp, the influenza-like illness secondary attack rate was 11% for children (5%-21%) and 4% for adults (2%-8%). The odds ratio for influenza-like illness among children versus adults was 3.1 (1.3-7.3).
CONCLUSIONS
The strong age effect, combined with the low number of susceptible children per household (1.2), plausibly explains the lower-than-expected household secondary attack rate for influenza-like illness, illustrating the importance of other venues where children congregate for sustaining community transmission. Quantifying the effects of age on pH1N1 transmission is important for informing effective intervention strategies.
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10.1097/EDE.0b013e3182060ca5
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pubmed_344_5608
|
Polymeric macromolecules of well-designed structures and specific properties open promising directions in the capillary entangled polymer electrophoresis. Pluronic F-127, as a thermoassociating polymer, possesses some unique properties that can be utilized in capillary entangled polymer electrophoresis of amino acids, peptides and proteins. In this study, we studied properties of Pluronic F-127 polymer as an additive to BGE for the separation of peptides and proteins. The influence of the thermoassociation on separation selectivity was studied. The addition of Pluronic caused severe instabilities of the electrical current and the signal of the UV detector. This study reveals remarkable positive effect of a low pressure applied to the inlet buffer vial during the analysis, which apparently stabilizes the electrical current and the detector signal. The effect of hydrodynamic flow induced by the pressure applied on the separation efficiency was studied and the significance of this effect was discussed. Pluronic F-127, as a representative of synthetic macromolecules, was compared with dextran, as a representative of natural polymers, in terms of separation power, selectivity and repeatability of migration times.
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10.1002/jssc.201000132
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pubmed_363_16546
|
OBJECTIVE AND METHODS
We retrospectively reviewed treatment and clinical outcome of thymic epithelial tumors of 64 patients over a 20-year period. Clinical staging of the tumor was done by according to Masaoka classification. Histological diagnosis of the tumors was done by according to the second edition of the WHO histologic classification system for thymic epithelial tumors. Survival rate was calculated after Kaplan-Meire method.
RESULTS
Median age of patients was 53.7 years (ranged from 16 to 81). There were 30 men and 34 women. Eighteen patients had auto-immuno diseases. Sixty-two patients underwent surgery. In 57 patients resection was complete (extended thymo-thymectomy), but in the other five incomplete. The operative approach was median sternotomy in 51 patients and video-assisted thoracoscopic surgery in 6. Stage II to IV patients had postoperative mediastinal irradiation. Stage III to IV patients had postoperative cisplatin (CDDP) based chemotherapy. Inoperable patients were treated by chemo-radiotherapy. There were 42 stage I, 7 stage II, 11 stage III, 3 stage IV a, 1 stage IV b. The 5-year/10-year survival rates were 93%/89%, 71%/71%, 68.5%/--in patients with stage I, II and III. There were 5 type A tumors, 8 type AB tumors, 11 type B1 tumors, 11 type B2 tumors, 9 type B3 tumors, 11 type C tumors, the respect 5-year survival rates were 100%, 100%, 87.5%, 60%, 85.7% and 90%. Masaoka stage II to IV patients classified in B2, B3 and C type except one case.
CONCLUSION
Histologic type B2, B3 and C tumors may reflect the invasive nature. Masaoka staging system and the WHO histologic classification may help the assessment and treatment of patients with thymic epithelial tumor.
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pubmed_363_16546
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pubmed_970_13729
|
BACKGROUND
Body composition is relevant for the health and work performance of firefighters. However, the behavior of these parameters has not been elucidated for groups of firefighters performing different tasks.
OBJECTIVES
To compare the anthropometric profile of military firefighters who perform administrative (ADM) or operational work .
METHODS
The sample comprised 121 (ADM = 50 and operational = 71) male military firefighters. Body mass (BM), body fat percentage (BFP), fat body mass, lean body mass, body mass index (BMI), waist circumference and somatotype were analyzed.
RESULTS
Intergroup difference was found for body mass (ADM = 78.5 kg - operational = 84.6 kg), BMI (ADM = 25.8 - operational = 27.2) and lean body mass (ADM = 61.9 kg - operational = 66.2 kg).
CONCLUSION
The groups exhibited differences in their anthropometric profile and BFP and BMI above the recommended range.
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10.5327/Z1679443520180122
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pubmed_1077_12034
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Meningioma accounts for approximately one-third of primary central nervous system tumors. Most meningiomas are benign, although up to one third are classified as atypical or malignant. We describe a 63-year Caucasian male presenting with pleural metastases from an intracranial meningioma. Distant metastases from meningiomas are infrequently found in clinical practice and mostly are associated with atypical or malignant meningiomas. There is no standard treatment; however surgical resection of both the primary and metastatic lesions is the safest therapy. The overall prognosis of atypical meningiomas is poor. Our patient died one week after discharge from our hospital.
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10.12688/f1000research.2-222.v1
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pubmed_708_6247
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Digestibility of dietary fibre (DF) and energy of three pale-seeded and one dark-seeded variety of Amaranthus caudatus were studied in balance experiments with growing rats. Effects of processing: popping, toasting and flaking were also examined. The pale seeds contained about 8% of DF and the black seeds about twice as much. The soluble DF fraction made up 33-44% of the total DF (TDF) fraction in the pale-seeded varieties, but only 18% in the black seeds. The monomer sugar composition of the DF was very similar in all products. However, the black seeds were very high in lignin, and DF of the black-seeded products were more resistant to digestion than that of the pale-coloured products. In the pale amaranth products digestible energy (DE) varied between 86 and 91%. In the dark-seeded products DE was lower, and there was a significant negative correlation (r = -0.92) between DE and TDF. Processing of pale seeds had only minor effects on TDF and DE, but increased the proportion of soluble DF and the digestibility of DF in one variety. The food intake tended to be lower in rats fed raw pale seeds compared with those consuming processed products, indicating the presence of heat-labile factors reducing palatability. In conclusion, the pale seeds had a lower content of DF than most cereal grains and the DF was more easily digested. As a source of energy, amaranth grains seem to be comparable to other cereals.
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10.1007/BF02193780
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pubmed_1122_16860
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New reference value studies for spirometry are commonly compared to existing reference value studies using average data derived from existing reference equations. Such comparisons are inherently flawed because they do not account for differences in distributions of the independent and dependent variables and they do not have identical methodologies. This study was undertaken 1) to derive reference equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) for natives of Mongolia and 2) to compare the Mongolian data with data from a 1981 reference study of Caucasians in Salt Lake City, UT, USA. Spirometry was performed on 344 (176 male, 168 female) healthy, nonsmoking urban natives of Mongolia to generate reference equations for FVC, FEV1, and FEV1/FVC. These data were compared with data from a 1981 reference study of Caucasians in Salt Lake City, using both an analysis of covariance of the raw data and parametric and nonparametric comparisons of a matched pair subset. Average measured forced vital capacity and forced expiratory volume in one second in native Mongolians were within 1-2% of the Caucasian predicted values. These small differences are not statistically significant in any of the multiple methods of comparisons. Power analysis suggests that, if real differences exist, the differences in forced vital capacity are <155 mL for males, <105 mL for females, and the differences in forced expiratory volume in one second are <107 mL for males and <76 mL for females.
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10.1183/09031936.99.13360699
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pubmed_140_456
|
OBJECTIVE
To assess the value of phase contrast magnetic resonance imaging cerebrospinal fluid flowmetry in differentiating between normal pressure hydrocephalus and involutional atrophy.
METHODS
The descriptive case-control study was conducted at the Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from April to December 2017, and comprised patients with normal pressure hydrocephalus and involutional brain changes. Healthy volunteers were included as controls. Demographic data was recorded and the patients were divided according to age. Conventional magnetic resonance imaging of the brain was performed followed by the assessment of cerebrospinal fluid flow dynamics, was done at the level of the aqueduct of Sylvius. Data was analysed using SPSS 25.
RESULTS
Of the 23 subjects with a mean age of 52.3}16.8 years (range: 25-75 years), There were 13(56.5%) males and 10(43.5%) were females. Also, there were 17(74%) patients and 6(26%) controls. Among the patients, 8(47%) had brain atrophic changes based on magnetic resonance imaging, and 9(53%) had normal pressure hydrocephalus signs clinically and scanning criteria. Flowmetry showed mean systolic velocity 1.5}0.3 cm\sec, peak systolic velocity 1.5}0.3 cm\sec and systolic stroke volume 28.5}4.7μLin the control group which was significantly different from the patients (p<0.001).
CONCLUSIONS
Phase-contrast magnetic resonance imaging was found to be a useful tool to differentiate between normal pressure hydrocephalus and age-related brain atrophy.
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pubmed_140_456
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pubmed_156_20808
|
Developmental competence of bovine oocytes collected from follicles of different size categories (in either the growth or the dominant phase of the first follicular wave) was studied, with the aim of improving in vitro embryo production. Estrus and ovulation of 39 cyclic Holstein dairy cows were synchronized by two prostaglandin F2alpha treatments at 11-day intervals and one hCG treatment on the day of onset of estrus (Day 0). Cows with follicles in either the growth (Day 3, n=25) or the dominant phase (Day 7, n=14) were slaughtered, and follicles >5 mm were counted. Three oocyte populations were recovered separately from large (11-15 mm), medium (6-10 mm) and small (2-5 mm) follicles in both follicular phases. All collected cumulus-oocyte complexes (COC), except for markedly atretic oocytes without cumulus cells, were used in experiments. Oocytes were matured, fertilized and cultured by standard methods. There were no significant differences between the growth and the dominant phases for mean numbers of large follicles, usable oocytes and embryos per donor. Generally, those numbers were low, but the development rates of oocytes into blastocysts were high, particularly in the growth phase (60.0%). Mean (+/- S.E.M.) numbers of medium follicles, oocytes and embryos per donor were higher in the growth as compared with the dominant phase; in the usable oocytes and embryos, this difference was significant (9.6 +/- 1.4 and 3.5 +/- 0.6 versus 3.9 +/- 0.6 and 1.1 +/- 0.3; P<0.01). The development rates of oocytes into blastocysts, however, did not differ significantly between the growth and the dominant phases (36.7% versus 27.8%). Mean numbers of usable oocytes and embryos per donor recovered from small follicles in both follicular wave phases were similar. The development rate of oocytes into blastocysts was generally low, but higher (P<0.01) in the growth than in the dominant phase (24.5% versus 11.7%). Comparison between the two phases showed that mean number of all counted follicles and all usable oocytes collected per donor were similar, but the mean number of embryos per donor and the development rate of oocytes into blastocysts were higher in the growth phase than in the dominant phase (8.0 +/- 1.2 versus 3.8 +/- 2.4; P=0.012 and 30.3% versus 14.9%; P<0.01). The interaction between follicle size and the phase of follicular wave affected the efficiency of embryo production. The yield of embryos was primarily influenced by the number of oocytes collected from medium follicles and the developmental competence of oocytes from small follicles. The growth phase was more effective for oocyte collection; the number of oocytes from medium follicles and the developmental competence of oocytes from small follicles decreased in the dominant phase.
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10.1016/s0093-691x(03)00216-4
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pubmed_315_18889
|
We carried out a prospective study of the effect of neurosurgical teleconsultations on patient management in northern Norway. The total number of teleradiology image transfers during an eight-month study period was 723. We recorded data on 99 (14%) of these teleconsultations, which concerned 92 patients; the remainder were transfers to other departments at our hospital and transfers of routine examinations from a small community hospital that did not have a radiologist. The neurosurgeon on call noted the clinical condition and response time for each consultation. The consequences of the teleconsultation and the eventual benefits of the image transfer were evaluated. All 10 referring hospitals in the region used the service. The median response time was 3 hours (range 1-21 hours) in emergency cases and 1 day (range 1-7 days) in ordinary consultations. The response time was significantly shorter for patients with head injuries (median 3 hours) than for those with intracranial tumours (median 24 hours). Image transfer was considered beneficial for the patient in 93% of the cases. Avoidance of unnecessary patient transfer, changes of treatment at the referring hospital on the advice of the neurosurgeon and initiation of emergency transfer occurred in 34%, 42% and 13% of cases, respectively. The results confirm that teleconsultations between referring hospitals and a regional neurosurgical service influence patient management and reduce the frequency of patient transfer.
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10.1258/135763304323070760
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pubmed_942_5792
|
Extracts of etiolated pea (Pisum sativum L.) shoots converted soluble pectin from the seedlings to a trichloroacetic acid-insoluble form. This activity coincided with pectinesterase peaks separated from the extracts by gel filtration and ion exchange. The conversion of pectin to the trichloroacetic acid-insoluble form and pectinesterase exhibited identical responses to pH, with activity only above pH 6. The formation of trichloroacetic acid-insoluble pectin in pea cell walls and their extracts is due to de-esterification of the pectin by pectinesterase and not to binding between pectin and a protein, as reported in the literature.
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10.1104/pp.76.2.547
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pubmed_709_13231
|
Two approaches were used to establish the intercellular distribution of fatty acid synthetase and thioesterase II in the lactating rat mammary gland. Thioesterase II is the chain-length regulatory enzyme in the biosynthesis of the medium-chain fatty acids characteristic of milk fat. Using immunohistochemical techniques, immunoreactive fatty acid synthetase was found in both mammary adipocytes and epithelial cells; in contrast, immunoreactive epithelial cells were isolated from lactating rat mammary glands after digestion with collagenase and thermolysin, and their lipogenic activity was studied using isotopically labelled acetate. Consistent with the immunohistochemical data, adipocytes synthesized exclusively long-chain fatty acids whereas epithelial cells synthesized predominantly chain fatty acids. The results indicate that the capacity for synthesis of medium-chain fatty acids is a unique property of the epithelial cell component of the mammary gland.
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10.1677/joe.0.0940251
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pubmed_732_19291
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We use a simple method for evaluating antioxidative status, by measuring the redox potential of urine, and correlate the findings with measures of anxiety and depression. We include 63 individuals (28 males and 35 females aged between 20 and 65 years). The validated anxiety State-Trait Anxiety Inventory questionnaire and the validated BDI (Beck Depression Inventory) questionnaire were used to evaluate anxiety and depression. Antioxidative status was determined by measuring the redox potential of urine collected in standard conditions. Correlation of the antioxidant capacity of urines evaluated using the ferric ion/specific dye method or through redox potential using the platinum electrode demonstrated the suitability of this last procedure. We found that normal anxiety state values corresponded to low urine redox potentials, whereas higher anxiety states were associated with high urinary redox potential. We also found that individuals with normal BDI values had significantly lower urine redox potentials than individuals with higher BDI values.
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10.1155/2014/430216
|
pubmed_936_14384
|
Lung adenocarcinoma (LUAD) is the main pathological subtype of non-small-cell lung cancer. Endoplasmic reticulum stress (ERS) has been found to be involved in multiple tumor-related biological processes. At present, a comprehensive analysis of ERS-related genes in LUAD is still lacking. A total of 1034 samples from TCGA and GEO were used to screen differentially expressed genes. Further, Random Forest algorithm was utilized to screen characteristic genes related to prognosis. Then, LASSO Cox regression was used to construct a prognostic signature. Taking the median of signature score as the threshold, patients were separated into high-risk (HR) group and low-risk (LR) group. Tumor mutation burden (TMB), immune cell infiltration, cancer stem cell infiltration, expression of HLA, and immune checkpoints of the two risk groups were analyzed. TIDE score was used to evaluate the response of the two risk groups to immunotherapy. Finally, the gene expression was verified in clinical tissues with RT-qPCR. An eight-gene signature (ADRB2, AGER, CDKN3, GJB2, SFTPC, SLC2A1, SLC6A4, and SSR4) was constructed. TMB and cancer stem cell infiltration were higher in the HR group than the LR group. TIDE score and expression level of HLA were higher in the LR group than the HR group. Expression level of immune checkpoints, including CD28, CD27, IDO2, and others, were higher in the LR group. Multiple drugs approved by FAD, targeting ERS-related genes, were available for the treatment of LUAD. In summary, we established a stable prognostic model based on ERS-related genes to help the classification of LUAD patients and looked for new treatment strategies from aspects of immunity, tumor mutation, and tumor stem cell infiltration.
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10.1155/2022/6567916
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pubmed_434_20501
|
BACKGROUND
The optimal duration of clopidogrel therapy after coronary stenting is debated because of the scarcity of randomized controlled trials and inconsistencies arising from registry data. Although prolonged clopidogrel therapy after bare metal stenting is regarded as an effective secondary prevention measure, the safety profile of drug-eluting stents itself has been questioned in patients not receiving ≥ 12 months of dual-antiplatelet therapy.
HYPOTHESIS
Twenty-four months of clopidogrel therapy after coronary stenting reduces the composite of death, myocardial infarction, or stroke compared with 6 months of treatment.
STUDY DESIGN
PRODIGY is an unblinded, multicenter, 4-by-2 randomized trial. All-comer patients with indication to coronary stenting are randomly treated-balancing randomization-with bare metal stent (no active late loss inhibition), Endeavor Sprint zotarolimus-eluting stent (Medtronic, Santa Rosa, CA) (mild late loss inhibition), Taxus paclitaxel-eluting stent (Boston Scientific, Natick, MA) (moderate late loss inhibition), or Xience V everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) (high late loss inhibition). At 30 days, patients in each stent group are randomly allocated to receive 24 or up to 6 months of clopidogrel therapy-primary end point randomization. With 1,700 individuals, this study will have >80% power to detect a 40% difference in the primary end point after sample size augmentation of 5% and a background event rate of 8%.
SUMMARY
The PRODIGY trial aims to assess whether 24 months of clopidogrel therapy improves cardiovascular outcomes after coronary intervention in a broad all-comer patient population receiving a balanced mixture of stents with various anti-intimal hyperplasia potency.
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10.1016/j.ahj.2010.07.034
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pubmed_109_3365
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Inlying tracheal "stay sutures" and submandibular sutures to prevent cervical hyperextension were used separately and in concert to limit anastomotic tension following tracheal resection in puppies. Study of the degrees of stenosis in the mature dogs indicates the effectiveness of the principle.
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pubmed_109_3365
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pubmed_322_23207
|
Orexinergic system consisting of orexins and orexin receptors plays an essential role in regulating sleep-wake states, whereas sleep disruption is a common symptom of a number of neurodegenerative diseases. Emerging evidence reveals that the orexinergic system is disturbed in various neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), whereas the dysregulation of orexins and/or orexin receptors contributes to the pathogenesis of these diseases. In this review, we summarized advanced knowledge of the orexinergic system and its role in sleep, and reviewed the dysregulation of the orexinergic system and its role in the pathogenesis of AD, PD, HD, and MS. Moreover, the therapeutic potential of targeting the orexinergic system for the treatment of these diseases was discussed.
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10.3389/fnagi.2021.713201
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pubmed_323_14193
|
BACKGROUND
With effective contraceptives available, unplanned pregnancies are preventable and educational interventions have been cited as a promising platform to increase contraceptive use through improving knowledge. However, results from trials of educational interventions have been disappointing. In order to effectively target future interventions, this study aimed to identify risk factors for unplanned pregnancy among young women in Mwanza, Tanzania.
METHODS
Data were analysed from the MEMA kwa Vijiana Trial Long-term Evaluation Survey, a cross-sectional study of 13,814 young adults aged 15-30 years in Mwanza, Tanzania. Potential risk factors for unplanned pregnancy were grouped under three headings: socio-demographic, knowledge of and attitude towards sexual health, and sexual behaviour and contraceptive use. Conditional logistic regression was used to identify predictors of reported unplanned pregnancy among all sexually active women.
RESULTS
Increasing age, lower educational level, not being currently married, knowing where to access condoms, increasing number of sexual partners and younger reported age at sexual debut were associated with unplanned pregnancy.
DISCUSSION
A number of demographic and sexual behaviour risk factors for pregnancy are identified which will help guide future intervention programmes aiming to reduce unplanned pregnancies. This study suggests effective measures to prevent unplanned pregnancies should focus on encouraging girls to stay in school.
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10.1136/jfprhc-2012-100389
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pubmed_405_3462
|
PURPOSE
To report a case of long-lasting hypotony because of accidental break, with scleral tunnel entrapment, of a 23-gauge microcannula during transconjunctival sutureless vitrectomy.
METHODS
Interventional case report. An 80-year-old Spanish woman who underwent 23-gauge transconjunctival sutureless vitrectomy presented at the postoperative ocular examination with irreversible, refractory low intraocular pressure of unknown cause. Two weeks after surgery, a piece of the microcannula was found at the inferotemporal sclerotomy site during a scheduled medical appointment. Surgical intervention was indicated to explore and remove the foreign body.
RESULTS
The day after foreign body extraction, the patient's pressure rose to normal levels. However, her visual acuity did not improve until 3 weeks later.
CONCLUSION
Transient postoperative hypotony is unsurprising after 23-gauge vitrectomy because of leakage of small-diameter open sclerotomies. However, when long-term low intraocular pressure fails to return to normal levels because of an unidentified condition, breaking of the microcannula piece with scleral tunnel entrapment may be contemplated.
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10.1097/ICB.0000000000000038
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pubmed_782_455
|
The enzymatic synthesis of α-amino acids is a sustainable and efficient alternative to chemical processes, through which achieving enantiopure products is difficult. To more address this synthesis efficiently, a hierarchical architecture that irreversibly co-immobilises an amino acid dehydrogenase with polyethyleneimine on porous agarose beads has been designed and fabricated. The cationic polymer acts as an irreversible anchoring layer for the formate dehydrogenase. In this architecture, the two enzymes and polymer colocalise across the whole microstructure of the porous carrier. This multifunctional heterogeneous biocatalyst was kinetically characterised and applied to the enantioselective synthesis of a variety of canonical and noncanonical α-amino acids in both discontinuous (batch) and continuous modes. The co-immobilised bienzymatic system conserves more than 50 % of its initial effectiveness after five batch cycles and 8 days of continuous operation. Additionally, the environmental impact of this process has been semiquantitatively calculated and compared with the state of the art.
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10.1002/cbic.201700493
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pubmed_1018_4567
|
Liver macrophages, which are involved in the different types of hepatitis, may indirectly induce hepatic fibrogenesis, since they have the possibility to activate hepatic stellate cells and fibroblasts by secretion of TGF-beta, TNF-alpha and IL-1. To evaluate variations of the number of liver macrophages and their subpopulations, a quantification was carried out in normal human liver tissue, fatty liver, fatty liver hepatitis and hepatitis B. Identification was performed by the mab PG-M1 (anti-CD68) and, comparatively, four lectins, Griffonia simplicifolia agglutinin I (GSA-I), Erythrina cristagalli agglutinin (ECA), peanut agglutinin (PNA) and soybean agglutinin (SBA). A slight decrease in the frequency of macrophages in pericentral fields was observable in fatty liver and fatty liver hepatitis as compared to normal liver tissue. On the other hand, the number of CD68+ cells was significantly enhanced in hepatitis B with moderate and severe inflammatory activity. The highest incidence of macrophages was found in portal tracts of liver with fatty liver hepatitis and, particularly, hepatitis B. The fraction of cells stained by ECA, PNA or SBA did not increase significantly under pathological conditions. In contrast, the percentage of GSA-I binding macrophages was higher in liver parenchyma of hepatitis B and in portal tract macrophages in fatty liver hepatitis and also hepatitis B. In conclusion, our results indicate that GSA-I may aid in the detection of the subpopulation of activated macrophages which are assumed to play a pivotal role in liver pathology.
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10.1155/1998/192975
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pubmed_75_1925
|
A comparative study of two arrhythmia models was carried out using coronary ligation and reperfusion in anesthetized rats and in isolated rat hearts. Both models allowed evaluation of the concentration-effect relationships of lidocaine as an antiarrhythmic agent. The average free plasma-water concentration that reduced the incidence of ventricular fibrillation by 50% was comparable in both models: 1.9 mg/liter in vivo and 2.1 mg/liter in vitro, respectively. In isolated rat hearts significantly higher concentrations were required for 50% reduction of ventricular tachycardia than for the suppression of ventricular fibrillation (2.9 +/- 0.13 versus 2.1 +/- 0.11 mg/liter, p less than 0.05). The good agreement between effective lidocaine concentrations in vivo and in vitro suggests that the isolated rat heart preparation is suitable for the quantitative assessment of drug effects on occlusion-reperfusion arrhythmias. A better reproducibility and easier control of drug concentrations are the advantages of the in vitro model.
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10.1016/0160-5402(86)90028-8
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pubmed_859_5771
|
As growing evidence implicates extra-renal mineralocorticoid receptor (MR) in cardiovascular disease (CVD), recent studies have defined both cell- and sex-specific roles. MR is expressed in vascular smooth muscle (SMC) and endothelial cells (EC). This review integrates published data from the past five years to identify novel roles for vascular MR in CVD, with a focus on understanding sex differences. Four areas are reviewed in which there is recently expanded understanding of the cell type- or sex-specific role of MR in: (1) obesity-induced microvascular endothelial dysfunction, (2) vascular inflammation in atherosclerosis, (3) pulmonary hypertension and (4) chronic-kidney disease (CKD)-related CVD. The review focuses on preclinical data on each topic describing new mechanistic paradigms, cell type-specific mechanisms, sexual dimorphism if addressed, and clinical implications are then considered. New data support that MR drives vascular dysfunction induced by cardiovascular risk factors via sexually dimorphic mechanisms. In females, EC-MR contributes to obesity-induced endothelial dysfunction by regulating epithelial sodium channel expression and by inhibiting estrogen-induced nitric oxide production. In males with hyperlipidemia, EC-MR promotes large vessel inflammation by genomic regulation of leukocyte adhesion molecules, which is inhibited by the estrogen receptor. In pulmonary hypertension models, MRs in EC and SMC contribute to distinct components of disease pathologies including pulmonary vessel remodeling and RV dysfunction. Despite a female predominance in pulmonary hypertension, sex-specific roles for MR have not been explored. Vascular MR has also has been directly implicated in CKD-related vascular dysfunction, independent of blood pressure. Despite these advances, sex differences in MR function remains understudied.
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10.1152/ajpcell.00372.2022
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pubmed_166_18952
|
The present study investigated the effect of triptolide on viability and apoptosis along with underlying mechanism in liver cancer cells. CCK-8 assay showed that triptolide treatment for 48 h significantly reduced the viability of HepG2 and QSG7701 cells at 50 µM concentration. Annexin V-FITC and propidium iodide staining showed that triptolide treatment of HepG2 cells at 50 µM concentrations induced apoptosis in 56.45% cells compared to only 2.36% cells in the control cultures. Western blot assay showed that treatment of HepG2 cells with 50 µM concentration of triptolide significantly induced phosphorylation of p53 in a 2 h-treatment. Phosphorylation of histone H2A.X indicator of DNA damage was induced by triptolide treatment after 12 h in HepG2 cells. The level of nuclear p53 in a 6 h-treatment with 0, 10, 20, 30, 40 and 50 µM concentration of triptolide was found to be 15.3, 19.6, 28.5, 43.7, 63.8 and 91.5%, respectively. Treatment of HepG2 cells with triptolide at 50 µM concentration caused a significant increase in the binding potential of p53 to DNA. Triptolide treatment of HepG2 cells caused a significant increase in the expression of p21, Bax and DR5 genes in HepG2 cells. It also increased the expression of miR-34b and miR-34c in HepG2 cells markedly. Treatment of HepG2 cells with p53 inhibitor, pifithrin-α prior to incubation with triptolide significantly prevented induction of cell apoptosis. Suppression of p53 expression by siRNA inhibited the expression of p53 as well as its target genes along with the prevention of apoptosis induction. In conclusion, triptolide inhibits viability and induces apoptosis in liver cancer cells through activation of the tumor suppressor gene p53. Thus, triptolide can be used for the treatment of liver cancer.
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10.3892/ijo.2017.3850
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pubmed_240_16688
|
Significant progress has been made during the past decade in preparing nanosheets from a wide range of materials, which are actively pursued for various applications such as energy storage, catalysis, sensing, and membranes. One of the next critical challenges is developing a robust and versatile assembly method which allows construction of the nanosheets into functional structures tailored for each specific purpose. An interesting characteristic of nanosheets is that they often behave as charged macromolecules and thus can readily interact with an oppositely charged polyelectrolyte to form a stable complex. In this report, we demonstrate how such a complexation process could be utilized for directing the self-assembly of nanosheets. By confining the nanosheet-polyelectrolyte complexation at air-liquid or liquid-liquid interfaces, the nanosheets are successfully assembled into various mesoscale architectures including fibers, capsules, and films. Furthermore, incorporation of additional components such as nanoparticles or small molecules can be easily achieved for further tailoring of material properties. This novel assembly method opens a pathway to many useful nanosheet superstructures and may be further extended to other types of nanomaterials in general.
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10.1021/nn303608g
|
pubmed_409_14531
|
Mixtures of D-glucosamine and glucose were used to slow the growth of wild-type and whi2 mutant strains of Saccharomyces cerevisiae without affecting the level of catabolite repression. The following observations were made. Firstly, mutant cells were found to be partially resistant to the inhibitory effect of glucosamine. Secondly, slow growth induced by glucosamine resulted in cells becoming larger, in direct contrast to the effect of slowing growth by glucose limitation in a chemostat or by carbon source substitution. It is concluded that the level of repression/derepression, rather than absolute growth rate, is responsible for controlling cell size. Thirdly, when WHI2 transcript levels were measured it was found that expression was correlated with growth rate rather than the level of repression. These results are interpreted in terms of a model which envisages that the WHI2 product acts as a negative regulator of catabolite repression. A test of this model is reported: it is shown that mutant cells respired more actively in the presence of glucose and grew more rapidly on glycerol, whereas overexpression of WHI2 from multicopy plasmids prevented growth on glycerol and depressed respiration.
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10.1099/00221287-136-4-733
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pubmed_416_18151
|
PURPOSE
To investigate whether electroacupuncture can prevent selenite-induced cataract in an experimental model.
METHODS
Fifty Wistar rat pups were randomized into 5 groups of 10 animals: Group 1 (control), no procedure was performed; Group 2 (selenite), sodium selenite (30 micromoles/kg body weight) was injected subcutaneously between postpartum days 10 to 12; Group 3 (anesthesia) received the same dose of selenite and underwent ether inhalation anesthesia during 10 minutes daily for one week; Group 4 (electroacupuncture) underwent the same procedure of Group 3, but also receiving electroacupuncture (2 Hz, 50 mA) applied to the Neiguan (PC6) and Guangming (GB37) acupoints during the anesthesia period; and Group 5 (Sham) underwent the same procedures of Group 4, but needles were applied to non-acupoints. The development of cataract was assessed one week later, and its density was graded by slit lamp biomicroscopy.
RESULTS
All control rats' lenses (Group 1) were clear. Groups 2, 3 and 5 rats developed more severe cataract or complete opacification. In Group 4 (electroacupuncture), 45% of eyes did not develop cataract while thirty per cent developed less severe cataract than Groups 2, 3 and 5. The between-group difference was statistically significant (p<0.001). Lens opacification grade in Groups 1 and 4 was lower than in the Groups 2, 3 and 5 (p<0.001).
CONCLUSION
Electroacupuncture effectively decreased selenite-induced cataract formation rate in pup rats when needles were applied at specific acupoints.
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10.1590/s0004-27492006000300003
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pubmed_397_7904
|
The hemoprotein content of 17 strains of Bradyrhizobium japonicum bacteroids from field-grown plants and the corresponding strains of cultured cells was determined spectrally. The major terminal oxidases, cytochromes (cyt) aa(3) and o, were present in all strains of cultured cells. cyt aa(3) was present in significant amounts in bacteroids only in strains of DNA homology group II. cyt o appeared to be present in bacteroids of all strains, and the average level was the same as in cultured cells. cyt b and c in the membrane fractions were higher in bacteroids of all strains compared with cultured cells. cyt P-450 was present in both the membrane and soluble fractions of bacteroids of most strains. The total P-450 content varied sixfold among strains. A CO-reactive hemoprotein, P-422, was present in the soluble fraction of all strains of cultured cells. P-422 may be a hemoglobinlike protein, and it was present in significant amounts in bacteroids only in DNA homology group I strains.
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10.1128/aem.56.9.2736-2741.1990
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pubmed_211_13596
|
The process of active dissociation or "DNA clearing" of not covalently binding agents from DNA in living HeLa cells was shown by the flow cytometry technique. The vital fluorescent bisbenzimidazole dye Hoechst 33342, which binds tightly but not covalently to DNA in a minor groove, was used as a basic model to study the interaction of not covalently binding agents with DNA. In this paper, we continue to analyse the "DNA clearing" process in the living fibroblasts of different rodent species (mouse, rat, Chinese hamster). The obtained data suggest that the processes of active dissociation or "DNA clearing" of Hoechst 33342 have some common features in all investigated mammalian cells. Nevertheless, some differences in the process were found in these lines. The role of nucleotide excision repair genes in the process of DNA clearing was not established.
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pubmed_211_13596
|
pubmed_964_15392
|
Class A amphipathic helical peptides have been shown to mimic many properties of exchangeable apolipoproteins. The three analogs of the class A amphipathic peptides were used to probe the structure and function of human very low density lipoproteins (VLDL): 1) 18 residue peptide possessing a single helical domain (18A) with the sequence Asp-Trp-Leu-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe; 2) two domains of 18A separated by a Pro (37pA); and 3) and 18A analog with the end groups protected to increase helicity (Ac-18A-NH2). Upon incubation of the peptides with VLDL at a peptide to VLDL, (protein) ratio of 1:1, the 37pA and Ac-18A-NH2 were able to displace most of apolipoprotein (apo) Cs and E from VLDL without alteration in its lipid composition and morphology while 18A had minimal effect. The extent of displacement was a function of the peptide to VLDL ratio. The rank order of displaceability of apolipoproteins on VLDL was apoE > C-III > C-II. The displacement of apoE and/or Cs from VLDL by peptides variably affected the ability of VLDL to interact with purified bovine milk lipoprotein lipase (LpL) and cultured macrophages. Treatment of VLDL with Ac-18A-NH2 markedly lowered its reactivity to LpL and its ability to induce lipid accumulation in cultured macrophages: however, treatment of VLDL with 37pA or 18A only minimally lowered their abilities. Ac-18A-NH2 treatment of VLDL resulted in the increase of apparent K(m) and a decrease of Vmax for lipoprotein lipase (LpL)-catalyzed hydrolysis of VLDL triglycerides. When an artificial triglyceride emulsion was used as a substrate of LpL, 37pA, but not Ac-18A-NH2, activated LpL. The above data indicate that 1) amphipathic helical peptides can alter the metabolic and functional properties of VLDL by dissociating the functionally important exchangeable apolipoproteins from VLDL as well as by acting as a functional element of VLDL after their incorporation; and 2) the class A amphipathic peptides having different lipid-associating properties exert significantly different effect on VLDL function.
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pubmed_964_15392
|
pubmed_690_21285
|
A kindred with a diabetic mother is described with one sibling with a radial deficiency (type 1 radial dysplasia (Bayne) with a hypoplastic thumb type 3 of Blauth) and one with an ulnar ray deficiency (type 2 of Ogden or type 1 of Swanson). A metabolic cause is probable, although the diabetes was well controlled during pregnancy.
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pubmed_690_21285
|
pubmed_406_7500
|
A case of prolonged reversible encephalopathy in a woman with arsenic poisoning is described. Previous descriptions of extended encephalopathy due to arsenic are rare.
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10.1212/wnl.28.8.853
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pubmed_548_16436
|
The detailed knowledge of excited state proton transfer mechanisms in complex environments is of paramount importance in chemistry. However, the definition of an effective reaction coordinate and the understanding of the driving force of the reaction can be difficult from both the experimental and the theoretical points of view. Here we analyzed by theoretical approaches the mechanism and the driving forces of the excited state proton transfer reaction occurring between the 7-hydroxy-4-(trifluoromethyl)coumarin photoacid and the 1-methylimidazole base molecules in toluene solution. In particular, we compared the intrinsic and the dynamical reaction pathways, obtained by integrating the reaction coordinate, and by performing ab initio simulations of molecular dynamics, respectively. Time-dependent density functional theory and polarizable solvation continuum models were adopted to define the excited state potential energy surface. Results were analyzed by means of the D(CT) electronic density based index. Our findings suggest that the reaction coordinate is mainly composed of several intra- and intermolecular modes of the reactants. An analysis of both the intrinsic coordinate and the dynamical results shows that the charge transfer induced by electronic excitation of the coumarin molecule is the main proton transfer driving force. With regards to the methodological validation, the combination of ab initio molecular dynamics with time-dependent density functional theory appears to be feasible and reliable to study excited state proton transfer reactions in the condensed phase.
|
10.1021/jp508947f
|
pubmed_433_9785
|
Actinobacterial strain CjT was directly isolated from soil beneath Ceanothus jepsonii growing in the USA. The strain formed cell structures typical of the genus Frankia including extensive hyphae, vesicles and sporangia, and it effectively nodulated members of the actinorhizal Colletieae, Elaeagnaceae and Myricaceae. The whole-cell hydrolysate of strain CjT was rich in meso-diaminopimelic acid and galactose, glucose, mannose, xylose, ribose and a trace of rhamnose. Tbe polar lipid profile contained phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol and glycophospholipid. The menaquinone was predominantly MK-9(H4). The fatty acid profile predominantly consisted of C17 : 1ω8c, iso-C16 : 0, C15:0, C16 : 0 and C17 : 0. A multilocus sequence analysis phylogeny based on atp1, ftsZ, dnaK, gyrA and secA gene sequences positioned the strain within Elaeagnaceae- and Colletieae-nodulating species together with Frankia elaeagni DSM 46783T, Frankia discariae DSM 46785T and Frankia irregularis DSM 45899T. Pairwise 16S rRNA gene sequence similarities showed that strain CjT was most closely related to F. discariae DSM 46785T (99.78 %) while their digital DNA-DNA hybridization value was 41.1 %. Based on the overall analyses, strain CjT (=DSM 100623T=CECT 9041T) warrants classification as the type strain of a novel species, for which the name Frankia soli sp. nov. is proposed.
|
10.1099/ijsem.0.003899
|
pubmed_24_15856
|
The authors explored the idea that teams consisting of members who, on average, demonstrate greater mastery of relevant teamwork knowledge will demonstrate greater task proficiency and observed teamwork effectiveness. In particular, the authors posited that team members' mastery of designated teamwork knowledge predicts better team task proficiency and higher observer ratings of effective teamwork, even while controlling for team task proficiency. The authors investigated these hypotheses by developing a structural model and testing it with field data from 92 teams (1,158 team members) in a United States Air Force officer development program focusing on a transportable set of teamwork competencies. The authors obtained proficiency scores on 3 different types of team tasks as well as ratings of effective teamwork from observers. The empirical model supported the authors' hypotheses.
|
10.1037/0021-9010.91.2.467
|
pubmed_196_20151
|
Agricultural practices like tillage and cropping sequence have profound influence on soil-living and plant-associated fungi, and thereby on plant growth. In a field experiment, we studied the effects of preceding crop and tillage on fungal communities in the soil and on young winter wheat roots in relation to plant winter survival and grain yield. We hypothesized that plant performance and fungal communities (described by amplicon sequencing) differ depending on tillage system and preceding crop; that the effect of preceding crop differs depending on tillage system, and that differences in fungal communities are reflected in plant performance. In line with our hypotheses, effects of preceding crop on plant growth and fungal communities on plant roots and in soil were more pronounced under non-inversion tillage than under inversion tillage (ploughing). Fungal communities on plant roots in treatments with low winter survival were different from those with better survival. In soil, several fungal OTUs (operational taxonomic units) differed significantly between tillage systems. OTUs representing putative plant pathogens were either more abundant (Parastagonospora sp._27) or less abundant (Fusarium culmorum/graminearum_5) after non-inversion tillage. Our findings highlight the influence of cultural practices on fungal communities and thereby on plant health and yield.
|
10.1093/femsle/fnz189
|
pubmed_236_11143
|
The hha gene of Escherichia coli was identified as modulating the expression of the haemolysin (hly) genes encoded by the recombinant plasmid pANN202-312. hha mutants harbouring plasmid pANN202-312 showed increased haemolysin production. The product of the hha gene, the Hha protein, shows strong homology to the YmoA protein of Yersinia enterocolitica, which plays a role in the thermoregulation of various Y. enterocolitica virulence genes. We show in this study that the Hha protein modulates the expression of haemolysin at the transcriptional level in cells harbouring plasmid pANN202-312. In addition, hha mutants show alterations in the level of plasmid DNA supercoiling. This suggests that the hha mutation increases haemolysin expression through changes in the DNA topology. This hypothesis is supported by our finding that gyr mutations, inhibitors of DNA gyrase such as novobiocin, or growth in conditions reported to reduce levels of negative supercoiling, such as low osmolarity medium, increase haemolysin production.
|
10.1111/j.1365-2958.1993.tb01230.x
|
pubmed_496_18902
|
One group of proteins that regulates neurite outgrowth and maintains neuronal networks is the immunoglobulin superfamily (IgSF). We previously identified a new member of the IgSF, keratinocyte-associated transmembrane protein-4 (KCT-4), by the signal sequence-trap method from primary cultured human keratinocytes. The KCT-4 mRNA has been found to be highly expressed in the adult human brain, although it is also distributed in various tissues. In the present study, to gain insight into the role of KCT-4 in the nervous system, we examined the expression profile and localization of KCT-4 mRNA in mouse brain. We also evaluated changes in KCT-4 mRNA expression in the differentiation of the neuroblastoma cell line Neuro-2a as the in vitro model of neurite outgrowth. KCT-4 mRNA was detected broadly in various regions of the adult mouse brain by RT-PCR. In situ hybridization revealed that it was expressed highly selectively by neurons but not by glial cells. Moreover, expression of KCT-4 mRNA was induced by neurite outgrowth of Neuro-2a. These data suggest that KCT-4 participates in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.
|
10.1016/j.neulet.2005.09.017
|
pubmed_614_21147
|
Urine has always been one of the most suitable body fluids for clinical applications. Absolute quantification of disease protein biomarkers in body fluids such as urine is a key step in the biomarker development pipeline. Nevertheless, identification of groups of proteins in complex biological samples is challenging. Traditional affinity-based methodologies such as ELISA are used to verify the presence of biomarkers in clinical samples. More recently, targeted mass spectrometry-based strategies have been developed for biomarker validation, offering an alternative. The great advantage of targeted mass spectrometry-based methodologies is that they allow accurate and specific simultaneous quantification of several biomarkers (multiplexing). Peptides are used as protein surrogates, measured using triple quadrupole instruments in selected reaction monitoring/multiple reaction monitoring mode. In this review, the workflow of selected reaction monitoring/multiple reaction monitoring for disease biomarker validation in urine is presented and assay performance in the latest studies is described.
|
10.1586/14737159.2015.1093937
|
pubmed_936_17311
|
OBJECTIVES
To determine whether higher levels of family connection are associated with a greater prevalence of flourishing in adolescence.
METHODS
We analyzed cross-sectional data from the International Survey of Children's Well-Being collected in 26 countries between 2016 and 2019 from 11- to 13-year-olds. Family connection was based on a mean score of 5 items that asked about care, support, safety, respect, and participation using a Likert-type scale (range 0-4). Flourishing was based on a mean score of 6 items that asked about self-acceptance, purpose in life, positive relations with others, personal growth, environmental mastery, and autonomy using a Likert-type scale (range 0-10). A mean score of >8 was considered flourishing.
RESULTS
The analysis involved 37 025 of 39 286 (94.2%) adolescents, after excluding those with missing data. The mean (SD) age was 11.9 (0.6) years and 51.4% were girls. The prevalence (95% confidence interval) of flourishing was 65.8% (65.3-66.3). Adolescents were distributed across 5 increasing levels of the family connection score: <2.5 (11.2%), 2.5 to <3.0 (8.8%), 3.0 to <3.5 (24.2%), 3.5 to <4.0 (25.1%), and 4.0 (30.7%). After controlling for covariates, including material resources and food sufficiency, the prevalence (95% confidence interval) of flourishing increased across the 5 levels of increasing family connection: 34.9% (33.3-36.5), 45.0% (43.2-46.8), 58.2% (57.2-59.3), 72.6% (71.6-73.5), and 84.3% (83.6-85.1), respectively.
CONCLUSIONS
Among adolescents from 26 countries, greater family connection was associated with a higher prevalence of flourishing. Family connection may contribute to flourishing, not just the avoidance of negative outcomes.
|
10.1542/peds.2021-055263
|
pubmed_82_1088
|
This study examined how religious/spiritual coping was related to specific conditions of caregiving and psychological distress among 127 informal caregivers to community-residing disabled elders. Support was found for the hypothesis that religious/spiritual coping influences caregiver distress indirectly through the quality of the relationship between caregiver and care recipient. Caregivers who used religious or spiritual beliefs to cope with caregiving had a better relationship with care recipients, which was associated with lower levels of depression and role submersion.
|
10.1093/geront/38.4.463
|
pubmed_199_11556
|
We have purified from Moloney murine leukemia virus (Mo-MuLV) a protease that has the capacity of accurately cleaving the polyprotein precursor Pr65gag into the mature viral structural proteins. Both the NH2- and COOH-terminal amino acid sequences have been determined and aligned with the amino acid sequence deduced from the DNA sequence of Mo-MuLV by other workers. The results show that: (i) the protease is located at the 5' end of the pol gene, and the first four amino acids are overlapped with the 3' end of the gag gene; (ii) the fifth amino acid residue is glutamine, which is inserted by suppression of the UAG termination codon at the gag-pol junction; and (iii) the protease is composed of 125 amino acids with calculated Mr = 13,315, and the COOH terminus of the protease is adjacent to the NH2 terminus of reverse transcriptase. The map order of the gag-pol gene is proposed to be 5'-p15-p12-p30-p10-protease-reverse transcriptase-endonuclease-3'.
|
10.1073/pnas.82.6.1618
|
pubmed_364_1972
|
The antioxidant, anti-inflammatory, and anticancer activities of Withania somnifera (WS) are known for a long time. This study was aimed to examine whether WS also diminishes 4-hydroxy-trans-2-nonenal (HNE)-induced neurotoxicity in human neuroblastoma (SH-SY5Y) cell line. The cytotoxic response of HNE (0.1-50 μM) and WS (6.25-200 μg/ml) was measured by MTT assay after exposing SH-SY5Y cells for 24 h. Then neuroprotective potential was assessed by exposing the cells to biologically safe concentrations of WS (12.5, 25, and 50 μg/ml) then HNE (50 μM). Results showed a concentration-dependent protective effect of WS at 12.5, 25, and 50 μg/ml against HNE (50 μM) induced cytotoxicity and cell inhibition. Pre-exposure to WS resulted in a strong inhibition of 24, 55 and 83% in malondialdehyde (MDA) level; 5, 27 and 60% in glutathione (GSH) level; 12, 36 and 68% in catalase activity; 11, 33 and 67% in LDH leakage; and 40, 80 and 120% in cellular LDH activity at 12.5, 25, and 50 μg/ml, respectively, induced by 50 μM HNE in SH-SY5Y cells. The HNE-mediated cellular changes (cell shrinkage, rounded bodies, and inhibition of outgrowth) and increased caspase-3 activity were also prevented by WS. The HNE-induced upregulation of proapoptotic markers (p53, caspase-3, and -9, and Bax) and downregulation of antiapoptotic marker Bcl-2 genes were also blocked by pretreatment with WS. Altogether, our findings indicate that WS possesses a protective potential against HNE-induced neurotoxicity.
|
10.1007/s11064-020-03146-4
|
pubmed_316_14209
|
Eleven murine monoclonal antibodies (MoAbs) were isolated that defined unique membrane antigens expressed on human melanoma cells but not detectable on human lymphoid cells by radioimmunometric assays. Five of these MoAbs each identified a separate melanoma cell surface antigen as shown by distinctly different in vitro MoAb binding patterns to a diverse panel of tumor cell lines. One of these 5 monoclonals, MoAb 34.1, reacted specifically with 9/11 melanoma lines and 0/28 other human tumor or lymphoid cell lines. The other 4 MoAbs reacted strongly with melanomas, but also bound to 1 or more non-melanoma lines. The remaining 6 MoAbs defined three distinct regions of a single melanoma cell membrane protein with a molecular weight of 125 kiloDaltons (kD) as shown by antibody crossblocking and gel electrophoresis. A sensitive radioimmunoassay developed with MoAbs to 2 epitopes of this 125 kD protein detected up to 500-fold higher levels of this antigen in extracts of melanoma cells compared to autologous lymphoid cells. The 125 kD antigen also was detected by indirect immunoperoxidase assays with the MoAbs on biopsied tumors in histologic tissue sections of 5/11 metastatic melanomas and 1/11 carcinomas but was found on some normal endothelium and smooth muscle. Another monoclonal, MoAb 705, reacted more broadly with tumor cells in 10/14 biopsied melanomas and 10/11 carcinomas, but also was reactive with basal epidermis and normal fibroblasts. By contrast, MoAb 34.1 bound specifically to tumor cells of 7/11 biopsied metastatic melanomas, but bound 0/10 carcinomas and few normal tissues except for some macrophages. Thus, MoAb 34.1 was the most specific diagnostic reagent for immunohistologic detection of melanoma. The 250 kD antigen defined by MoAb 34.1 is similar to a high molecular weight proteoglycan reported to be an excellent tumor marker for human melanomas. The results of these studies show that murine monoclonal antibodies can be used as sensitive reagents for radioimmunoassays and immunohistology of malignant melanoma.
|
pubmed_316_14209
|
pubmed_31_7673
|
BACKGROUND
Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018.
METHODS
A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET.
RESULTS
This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups.
CONCLUSIONS
Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.
|
10.1186/s12885-018-5040-z
|
pubmed_368_6638
|
A common feature of neurological diseases is the loss of central neurons, which leads to deafferentation of connected brain regions. In turn, the remodeling of denervated neuronal networks is considered to play an important role for the postlesional recovery, but has also been linked to maladaptive plasticity resulting in disease-related complications such as memory dysfunction or epilepsy. Recent work has indicated that Protease-Activated Receptor 1 (PAR1), which can be activated by thrombin that enters the brain under pathological conditions, alters synaptic plasticity and neuronal excitability. However, the role of PAR1 in lesion-induced synaptic plasticity remains incompletely understood. Here, we used entorhinal denervation of organotypic hippocampal slice cultures to study the effects of PAR1 on denervation-induced homeostatic synaptic plasticity. Our results disclose that PAR1 activation counters the ability of denervated dentate granule cells to increase their excitatory synaptic strength in a compensatory, i.e., homeostatic manner. Furthermore, we demonstrate that this PAR1 effect is rescued by pharmacological inhibition of N-methyl-d-aspartate receptors (NMDA-R). Thus, NMDA-R inhibitors may restore the ability of denervated neurons to express homeostatic synaptic plasticity under conditions of increased PAR1-activity, which may contribute to their beneficial effects seen in the context of neurological diseases.
|
pubmed_368_6638
|
pubmed_700_18308
|
A conceptual model is proposed for the genetic evolution of many human solid tumors that is based on the observations that cancer cells may spontaneously double their chromosome number; that cells with excessive chromosome numbers may be cytogenetically unstable, both losing chromosomes randomly during subsequent cell divisions, and often developing structural abnormalities in the chromosomes that are retained; and that some structural chromosome abnormalities may activate growth-promoting genes. The sequence of tetraploidization with chromosome loss can occur repeatedly in a given tumor. The available evidence supporting the model is reviewed. A computer simulation system that embodies these concepts is described and the model is used to generate distributions of chromosome number/cell under various simulated conditions and in a variety of simulated biological settings. A simulation of the time course of changes in chromosome number per cell that accompany the spontaneous neoplastic transformation of mouse fibroblasts in vitro is described. The best fit to the data was obtained when provision was made for the activation of at least two growth-promoting genes. The conditions for generating discrete aneuploid peaks in cytogenetic and flow cytometric studies were explored; our modeling studies suggest that the activation of a growth promoting gene is required in order to produce a discrete aneuploid peak. Our modeling studies suggest that the overrepresentation of individual oncogene-bearing chromosomes in aneuploid cell lines may require the activation of gene dose-dependent growth-promoting genes and is not likely to occur in cell lines in which at least two copies of each normal chromosome are required for cell survival. Overall, the results obtained using the model are consistent with a wide variety of flow cytometric and cytogenetic studies in human solid tumors.
|
pubmed_700_18308
|
pubmed_480_3870
|
OBJECTIVE
The aim of this study was to assess the frequency of cement residues after cementation of CAD/CAM monolithic zirconia crowns on customized CAD/CAM titanium abutments.
MATERIALS AND METHODS
Sixty premolars and molars were restored on Astra Tech Osseospeed TX™ implants using single monolithic zirconia crowns fixed on two types of custom-made abutments: Atlantis™ titanium or Atlantis™ Gold Hue. Occlusal openings providing access to the abutment screws were designed for retrievability of the crown/abutment connection. After fixation with glass ionomer cement, the crown/abutment units were unscrewed to evaluate the presence of residual cement. Dichotomous assessment of the presence or absence of cement at the crown/abutment unit and peri-implant tissues was performed.
RESULTS
Clinically undetected cement excess was visible on 44 of 60 restorations (73.3%). There was no interdependency between residual cement presence and implant location or diameter. However, a dependency between the presence of residual cement and the aspect of the abutment/crown connection could be noted. The majority of the residues were observed on the distal (17.9%) and mesial (15%) aspects. While on the palatal/lingual aspect, the cement was visible in 8.8%; only 3.4% of all surfaces displayed cement residues.
CONCLUSIONS
Within the limitations of the study, it can be concluded that the use of customized CAD/CAM abutments do not guarantee avoidance of subgingival cement residues after crown cementation.
|
10.1111/clr.12879
|
pubmed_688_16250
|
We present the results of a survey on the late effects of poliomyelitis in 201 persons. The most common new problems were fatigue, weakness in previously affected and unaffected muscles, muscle pain, and joint pain. The median time from poliomyelitis to onset of new problems ranged from 30 to 40 years. Factors at onset of polio most strongly associated with development of these late effects of polio were (1) hospitalization (P less than 0.00001), (2) age greater than 10 years (P less than 0.00001), (3) ventilator use (P less than 0.0029), and (4) paralytic involvement of all four limbs (P less than 0.0240). The differential diagnosis of these new problems, implications for treatment, and areas for future research are discussed.
|
pubmed_688_16250
|
pubmed_824_14306
|
OBJECTIVE
We investigated the use of autologous platelet-rich plasma (PRP) to improve the success rate of fat graft myringoplasty in perforated tympanic membranes of rats.
MATERIALS AND METHODS
A total of 20 healthy Wistar albino female rats were divided into two groups. In Group 1, the left tympanic membranes were perforated and grafted with a fat graft that was harvested from the inguinal region. In Group 2, the left tympanic membranes were perforated, and a fat graft was also harvested from the inguinal region. Then, the fat was soaked in 0.5 mL PRP and grafted at the perforation. After the procedure, the rats were examined, and the graft situation was assessed at 3, 5, 7, 10, and 14 days. All of the rats were sacrificed 21 days after perforation, and a histopathological examination was made.
RESULTS
We compared fat graft histopathological and otomicroscopic findings between the groups. While we did not observe graft rejections in Group 2, we saw 1 case of graft rejection in Group 1. In the histopathological examination, PRP prevents fat graft resorption by the terms of the adipocyte area, granulation tissue area, and vacuolization area.
CONCLUSION
This study demonstrated the efficacy of fat grafts prepared with PRP on rat tympanic membranes. The fat graft with PRP did not statistically improve the success rate compared to the graft without PRP. Histopatologic findings of the study showed that PRP prevents fat graft resorption. Further studies are needed to further examine the advantages of the graft with PRP.
|
10.5152/iao.2017.3845
|
pubmed_319_7687
|
Translational repression and mRNA degradation are two major mechanisms for post-transcriptional regulation of gene expression. The detailed relationship between these two processes is not yet well established. Zinc-finger antiviral protein (ZAP) inhibits the replication of certain viruses, including human immunodeficiency virus 1, by binding directly to specific viral mRNAs and recruiting cellular mRNA degradation machinery to degrade the target mRNA. Here, we report that ZAP also inhibits the translation of target mRNAs by interfering with the interaction between translational initiation factors eIF4G and eIF4A. Furthermore, we provide evidence that translational repression is required for mRNA degradation and that blocking the degradation of target mRNAs does not affect ZAP-mediated translational repression. We conclude that ZAP can both repress translation and promote degradation of target mRNA, and that translational repression precedes and is required for mRNA degradation.
|
10.1038/emboj.2012.271
|
pubmed_957_26589
|
Polyoxometalates (POMs) as molecule-based metal oxides have exhibited significant application in catalysis and materials science, but the synthesis of pristine POM nanomaterials still remains a challenge. In this work, we find a novel strategy of concentration-induced self-assembly for gaining pristine POM nanorods Ag H3- PMo12O40 (denoted as AgHPMo12), which are synthesized only from both POMs and silver ion Ag+ in an aqueous solution at room temperature. The controllable concentrations of the cationic and anionic components in the aqueous solution become the critical factor for the successful synthesis. In addition, the photoelectric properties of AgHPMo12 nanorods were investigated as compared to those of AgHPMo12 particles, indicating a superior photoelectric performance of AgHPMo12 nanorods to AgHPMo12 particles. Furthermore, AgHPMo12 nanorods/phthalocyanine heterojunction photocatalysts were prepared for evaluating photocatalytic degradation of tetracycline hydrochloride, showing an efficient photocatalytic performance due to the advantages of the nanorods and type II heterostructure.
|
10.1039/d0na00816h
|
pubmed_604_5959
|
The substituent effects on diastereoselective formation of fulleroids in the reactions of C(60) with various unsymmetrical diazoalkanes were investigated. The steric demand on the stereochemical course of reactions dominated the diastereoselectivity for diazoalkanes bearing aliphatic as well as monosubstituted pi-resonating groups, whereas the stereoelectronic effects of coexisting pi-resonating aromatic and cyclopropyl groups played a crucial role in the ring closure of the radical intermediates, overriding the steric demand.
|
10.1021/ol701789u
|
pubmed_265_1346
|
Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.
|
10.1128/JCM.36.5.1333-1337.1998
|
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