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1.
PAPER CURRENT
White matter injury in the preterm infant: pathology and mechanisms (2017)
Springer
Publication Date: 2017-05-23
Description: The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
Topics: Medicine
Published by Springer
2.
PAPER CURRENT
Ultra-Sensitive Measurement of IL-17A and IL-17F in Psoriasis Patient Serum and Skin (2017)
Springer
Publication Date: 2017-05-23
Description: Interleukin 17 is a family of cytokines that play a central role in many autoimmune and inflammatory diseases. IL-17A has been implicated as a key driver of psoriasis, mediating a chronic cycle of T-cell activation, keratinocyte proliferation and angiogenesis. It has been hypothesized that expression of IL-17A and the related cytokine IL-17F could be used as predictive biomarkers for therapeutic response, though they have been difficult to measure locally or in circulation because of their low abundance. We developed ultrasensitive methods for measuring IL-17A and IL-17F in human serum samples and found that serum from psoriasis patients had higher and a broader range of concentrations of both IL-17 proteins compared to healthy volunteers. We also adapted these methods for tissue biopsies and saw higher concentrations of both IL-17 proteins in psoriatic lesions, but they were undetectable in non-lesional skin from the same patients.
Electronic ISSN: 1550-7416
Topics: Chemistry and Pharmacology
3.
PAPER CURRENT
Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples (2017)
Springer
Publication Date: 2017-05-23
Description: Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Taking advantage of the immune system’s ability to generate highly specific antibodies, the field has turned to anti-idiotype antibodies as powerful tools for the development of sensitive and specific bioassays. Here, we report the generation and characterization of a highly specific neutralizing anti-idiotype antibody directed against M9346A, the antibody moiety of mirvetuximab soravtansine. The anti-idiotype antibody recognizes M9346A with double-digit picomolar affinity, competes with folate receptor antigen for binding to M9346A, and can be used to develop both anti-drug-antibody and neutralizing antibody assays.
Electronic ISSN: 1550-7416
Topics: Chemistry and Pharmacology
4.
PAPER CURRENT
Electrostatic Spray Ionization from 384-Well Microtiter Plates for Mass Spectrometry Analysis-Based Enzyme Assay and Drug Metabolism Screening (2017)
American Chemical Society (ACS)
Publication Date: 2017-05-23
Description: Analytical Chemistry DOI: 10.1021/acs.analchem.7b00536
Print ISSN: 0003-2700
Electronic ISSN: 1520-6882
Topics: Chemistry and Pharmacology
5.
PAPER CURRENT
2D IR Correlation Spectroscopy in the Determination of Aggregation and Stability of KH Domain GXXG Loop Peptide in the Presence and Absence of Trifluoroacetate (2017)
American Chemical Society (ACS)
Publication Date: 2017-05-23
Description: Analytical Chemistry DOI: 10.1021/acs.analchem.6b04800
Print ISSN: 0003-2700
Electronic ISSN: 1520-6882
Topics: Chemistry and Pharmacology
6.
PAPER CURRENT
Comparative Evaluation of Small Molecular Additives and Their Effects on Peptide/Protein Identification (2017)
American Chemical Society (ACS)
Publication Date: 2017-05-23
Description: Analytical Chemistry DOI: 10.1021/acs.analchem.6b04886
Print ISSN: 0003-2700
Electronic ISSN: 1520-6882
Topics: Chemistry and Pharmacology
7.
PAPER CURRENT
Immunofluorescence Imaging Strategy for Evaluation of the Accessibility of DNA 5-Hydroxymethylcytosine in Chromatins (2017)
American Chemical Society (ACS)
Publication Date: 2017-05-23
Description: Analytical Chemistry DOI: 10.1021/acs.analchem.7b01428
Print ISSN: 0003-2700
Electronic ISSN: 1520-6882
Topics: Chemistry and Pharmacology
8.
PAPER CURRENT
The Relationship of the Subtypes of Preterm Birth with Retinopathy of Prematurity (2017)
Elsevier
Publication Date: 2017-05-23
Description: Publication date: Available online 22 May 2017 Source: American Journal of Obstetrics and Gynecology Author(s): Anne M. Lynch, Brandie D. Wagner, Jennifer K. Hodges, Tamara S. Thevarajah, Emily A. Mccourt, Ashlee M. Cerda, Naresh Mandava, Ronald S. Gibbs, Alan G. Palestine Background Retinopathy of prematurity (ROP) is an adverse outcome of preterm birth (PTB) and is a leading cause of childhood blindness. The relationship between the subtypes of PTB with ROP is understudied. Objective To investigate if there is a difference in the incidence of type 1 or type 2 ROP in infants with PTB resulting from spontaneous preterm labor (SPTL), a medical indication (MIPTB), or preterm-premature rupture of the membranes (PPROM). Study Design A retrospective cohort study of 827 infants screened for ROP who delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for ROP defined as “infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for ROP.” Two independent reviewers masked to ROP outcomes determined if PTB resulted from SPTL, MIPTB or PPROM. Discrepancies were resolved by a third reviewer. Data were analyzed using univariate and multivariable logistic regression. Results In our cohort, the frequency of preterm birth resulting from SPTL, MIPTB or PPROM was: 34%, 40%, and 26% respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the PTB subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days – 36 weeks, 4 days); SPTL, 28 weeks 1 day ± 2 weeks, 3 days (23 weeks, 3 days – 33 weeks, 4 days); MIPTB, 29 weeks, 1 day ± 2 weeks, 2 days (24 weeks - 36 weeks, 4 days); PPROM, 28 weeks,4 days ± 2 weeks,1 day. (24 weeks – 33 weeks, 1 day). Among infants with type 1, type 2 or no ROP, the incidence of type 1 or type 2 ROP in births from SPTL, MIPTB and PPROM was: 37/218 (17%), 27/272 (10%), and 10/164 (6%), respectively. Adjusted for gestational age, birth weight and multiparity and compared to the PPROM group, the odds ratios of SPTL and MIPTB for type 1 or type 2 ROP were: 6.1 (95% CI 1.8-20, P = 0.003) and 5.5 (95% CI = 1.4-21, P = 0.01), respectively. Among neonates born after PPROM the probability of developing type 1 or type 2 ROP was highest in infants with rupture of membrane duration of up to 24 hours. After 24 hours, the probability of developing type 1 or type 2 ROP declined. The odds of developing type 1 or type 2 ROP was 9.0 [95% confidence interval (CI) = 2.3 – 34, P= 0.002] in infants who had a PPROM ≤ 24 hours compared with infants who had a PPROM > 24 hours. Conclusions Type 1 or type 2 ROP are adverse ocular outcomes linked with not only lower gestational age and birth weight at delivery but also with events in the intra-uterine environment that trigger a PTB. The reduced incidence of type 1 or type 2 ROP in the PPROM group compared to other causes of PTB may be related to the perinatal therapies associated with PPROM (such as corticosteroids, antibiotics, maternal-fetal surveillance), which may have an inhibitory effect on the development of ROP. We suggest that the physiologic events which predispose infants to type 1 or type 2 ROP begin prior to delivery.
Print ISSN: 0002-9378
Electronic ISSN: 1097-6868
Topics: Medicine
Published by Elsevier
9.
PAPER CURRENT
This Month in AJP (2017)
Elsevier
Publication Date: 2017-05-23
Description: Publication date: Available online 22 May 2017 Source: The American Journal of Pathology Teaser The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology .
Print ISSN: 0002-9440
Electronic ISSN: 1525-2191
Topics: Medicine
10.
PAPER CURRENT
Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background (2017)
Springer
Publication Date: 2017-05-23
Description: The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N -acetyl- S -(carbamoylethyl)- l -cysteine (AAMA) and N -acetyl- S -(1-carbamoyl-2-hydroxyethyl)- l -cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n  = 6) ingested AA via coffee (0.15–0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1–15.9 μg/kg bw) on day 10. The other arm (group B) was on AA minimized diet (washout, 0.05–0.06 µg/kg bw) throughout the whole 13-day study period. On day 6, these volunteers ingested 13 C 3 D 3 -AA (1 μg/kg bw). In both arms, urinary MA excretion was continuously monitored and blood samples were taken to determine hemoglobin adducts. Ingestion of four cups of coffee resulted in a slightly enhanced short-term biomarker response within the background range of group B. At the end of the 13-day washout period, group B excreted an AAMA baseline level of 0.14 ± 0.10 µmol/d although AA intake was only about 0.06 µmol/d. This sustained over-proportional AAMA background suggested an endogenous AA baseline exposure level of 0.3–0.4 µg/kg bw/d. The excretion of 13 C 3 D 3 -AA was practically complete within 72–96 h which rules out delayed release of AA (or any other MA precursor) from deep body compartments. The results provide compelling support for the hypothesis of a sustained endogenous AA formation in the human body.
Print ISSN: 0340-5761
Electronic ISSN: 1432-0738
Topics: Medicine
Published by Springer