bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope Mapping of the Anti-Urokinase Monoclonal Antibody 5B4 by Isolated Domains of Urokinase
Authors: Corti Angelo , Sarubbi Edoardo , Soffientini Adolfo , Nolli M Luisa , Zanni Arturo , Galimberti Marina , Parenti Franco , Cassani Giovanni 
Published: June 2018

SummaryThe amino terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) is a degradation product comprising the entire growth factor-like and kringle domains. It has been previously shown that ATF is able to bind to the u-PA receptor through the growth factor-like domain and that the anti u-PA monoclonal antibody 5B4 (Mab 5B4) binds to ATF preventing u-PA receptor binding. To localize more precisely the epitope recognized by Mab 5B4, ATF was subfragmented by controlled enzymatic proteolysis with V8 protease.Three subfragments of 4,000 Mr (F-4k), 11,000 Mr (F-llk) and
12,0 Mr (F-12k) were purified from the reaction mixture and characterized. SDS-PAGE under reducing and non-reducing conditions, N-terminal aminoacid sequence analysis and C-terminal aminoacid analysis of each fragment indicate that F-4k and F-llk correspond to intact growth factor-like domain and kringle domain (residues 4-43 and 44-135 respectively) while F-12k corresponds to the kringle. domain cleaved in the first loop at the glu52-gly53 bond.By Western blot and competitive binding experiments we show that Mab 5B4 recognizes an epitope located on the kringle domain of u-PA and that the binding is strongly reduced when the kringle contains an additional cleavage in its first loop.Since the receptor binding site of u-PA has been previously shown to be located on the growth factor-like domain, Mab 5B4 inhibits the binding of uPA to its cellular receptor likely by steric hindrance.Besides the proven utility in epitope localization of anti u-PA monoclonal antibodies, these u-PA fragments may represent powerful tools for studies of structure-function relationship of u-PA.
Aggregation to Thrombin and Collagen of Platelets from a Glanzmann Thrombasthenic Patient Lacking Glycoproteins IIb and IIIa
Authors: McGregor Lilian , Hanss Michel , Sayegh Amal , Calvette Juan J , Trzeciak Marie-Christine , Ville Danielle , Catimel Bruno , Viala Jean-Jacques , Dechavanne Marc , McGregor John L 
Published: June 2018

SummaryThe aim of this study was to investigate the platelets of a Glanzmann thrombasthenic patient, which in citrated PRP failed to respond to various agonists, but aggregated and secreted to high concentrations of thrombin (0.36, 0.72 and 1 U/ml) and collagen (4, 10 and 20 μg/ml) when washed and resuspended in a Tyrode-albumin solution (containing 2 mM Ca2+). Aggregation of the patient platelets was not affected by anti-IIb/IIIa monoclonal antibody (P18) which strongly inhibits thrombin or collagen induced aggregation of normal platelets. Washed platelets of this patient did not aggregate to ADP (10-100 μM) in the presence of added fibrinogen (2 mg/ml) nor bind 125I-labelled fibrinogen (40 to 320 μg/ml) when thrombin-stimulated. Different anti-IIb/IIIa monoclonal antibodies (P2, P18) when used in binding or crossed immunoelectrophoretic studies showed a complete absence of the IIb-IIIa glycoprotein complex on the patient platelets. Moreover, glycoproteins IIb or IIIa were absent on silver-stained twodimensional (non-reduced/reduced) polyacrylamide gel separations of the patient platelets and were not detected by Western blots used in combination with anti-PLA1 (antigen present on Ilia), anti-Leka (antigen present on IIb). This study shows that platelets lacking glycoproteins IIb or IIIa can aggregate in response to high concentrations of collagen or thrombin when resuspended in the presence of physiological concentrations of calcium. Results obtained in this study could indicate the existence of other mechanisms (other than the IIb-IIIa glycoprotein complex) involving glycolipids, heparans, proteoglycans, and/or unknown membrane glycoproteins to mediate platelet aggregation of stimulated thrombasthenic platelets.
Effect of the Concentration of Ca2+ in the Suspending Medium on the Responses of Human and Rabbit Platelets to Aggregating Agents
Authors: Packham M A , Bryant N L , Guccione M A , Kinlough-Rathbone R L , Mustard J F 
Published: June 2018

SummaryThe effect of the concentration of Ca2+ in the suspending medium of human and rabbit platelets on aggregation, release of 14C-serotonin, and TXB2 formation in response to ADP, thrombin, l-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (PAF), collagen and arachidonic acid was studied in either platelet-rich plasma anticoagulated with D-phenylalanyl-prolyl-arginyl chloromethylketone (PPACK) or citrate, or suspensions of washed platelets in modified Tyrode-albumin solutions containing 1 mM Mg2+ and concentrations of added Ca2+ ranging from 0 to 5 mM. In response to ADP, thrombin, or PAF, human platelets were stimulated to form TXA2 by close platelet contact in a low- Ca2+ medium; at physiological concentrations of Ca2+, TXB 2formation was much less and declined progressively as the concentration of Ca2+ was raised. When the formation of TXA 2was blocked with aspirin or indomethacin, aggregation and release by human platelets were strongest at physiological concentrations of Ca2+. Rabbit platelet responses differed markedly from those of human platelets because close contact of rabbit platelets in a low-Ca2+ medium did not promote TXA2 formation. Rabbit platelet responses were more strongly inhibited by the lack of added Ca2+ in the medium than the responses of human platelets, possibly because rabbit platelets do not contain releasable Ca2+.In all studies of human platelets in media with low concentrations of Ca2+, the additional contribution to platelet responses of TXA2 formed because of close platelet contact should be considered because TXA2 formation is not usually stimulated in this way at physiological concentrations of Ca2+. When TXA2 formation is blocked, aggregation and release responses to all agonists are greatest at physiological concentrations of Ca2+. Thus, the responses of human platelets in media with low concentrations of Ca2+ (citrated platelet-rich plasma or artificial media to which no Ca2+ has been added) are abnormal in at least two ways, and do not correspond to the responses at physiological concentrations of Ca2+.
Failure of Preactivated Human Blood Platelets to Restore Defective Thromboxane Synthesis despite Prolonged Incubation in Plasma
Authors: Stockschläder Marcus , Scharf Rüdiger E 
Published: June 2018

SummaryAcquired platelet storage pool disease has been shown to be associated with reduced platelet thromboxane synthesis. However, the mechanisms for this dysfunction are incompletely understood. The present experiments were designed to evaluate some of the possible defects which may account for impaired thromboxane formation in human platelets previously exposed to thrombin in vitro. Washed platelets pretreated with 0.5 U/ml thrombin for 20 sec and subsequently recovered as single degranulated platelets were incapable of forming normal amounts of thromboxane upon a second stimulation with thrombin (as compared to Tyrode-pretreated control platelets). In contrast, thrombin-degranulated platelets released additional amounts of thromboxane in response to arachidonate, or collagen, indicating that short-time exposure to thrombin does not irreversibly inactivate platelet cyclooxygenase or thromboxane synthetase. Upon incubation of the thrombin-pretreated platelets in autologous plasma in the presence of 14C-arachidonate, the label became associated with the platelets to the same extent as with control platelets. However, the platelets did not recover their ability to synthesize normal amounts of thromboxane upon restimulation with thrombin, and only about half of the label was lost from the thrombin-pretreated platelets as compared to control platelets in response to thrombin. The ability of collagen to cause loss of 14C-arachidonate and formation of thromboxane was the same regardless of whether or not the platelets had been pretreated with thrombin. Incubation of platelets in plasma in the presence of added arachidonate for 90 min resulted in complete refractoriness to a second stimulation with thrombin but not with collagen. However, the control platelets also lost most of their ability to synthesize thromboxane when incubated with arachidonate for 90 min and thereafter stimulated with thrombin. Thus, the presence of added arachidonate affects the thrombin-inducible thromboxane synthesis after prolonged incubation of human platelets in plasma. Our observations suggest that depletion of endogenous arachidonate is not a major cause for the defective thrombin-induced thromboxane synthesis in thrombin-pretreated platelets. It is more likely that impaired mobilization of endogenous arachidonic acid explains this dysfunction. Defective mobilization of arachidonate in thrombin-degranulated platelets may be due to agonists-specific receptor desensitization, but the responsible mechanism has not been identified.
Adhesion of Polymorphonuclear Leukocytes to Protein-Coated and Platelet Adherent Surfaces
Authors: Morley D J , Feuerstein I A 
Published: June 2018

SummarySince protein adsorption and platelet adhesion are likely to precede significant contact of leukocytes with the surfaces of artificial organs, we have chosen to study polymorphonuclear leukocyte (PMN) adhesion in a sequential manner. The work presented here deals with the effects of flow and surface type on PMN adhesion to fibrinogen- and albumin-coated glass. We compared direct adhesion to adsorbed protein with adhesion to adsorbed protein having adherent platelets. These experiments were designed to see if PMN's might preferentially adhere to albumin or fibrinogen and whether a particular morphological form of adherent platelet could promote PMN adhesion. The adhesion of PMN's to spread platelets on albumin or fibrinogen occurs to a greater extent than in the absence of platelets. Adhesion of PMN's to spread platelets may be an important mechanism for their depletion from the circulation during artificial organ use. .
Procoagulant Activity of Endocardial Vegetations and Blood Monocytes in Rabbits with Streptococcus sanguis Endocarditis
Authors: Buiting A G M , Thompson J , van der Keur D , Schmal-Bauer W C , Bertina R M 
Published: June 2018

SummaryTo investigate activation of the coagulation system in bacterial endocarditis, we determined the procoagulant activity of blood monocytes isolated from rabbits with Streptococcus sanguisinfected or sterile catheter-induced endocardial vegetations. This activity was determined directly after isolation from the peripheral blood and after stimulation in vitro by either endotoxin or by phagocytosis of S. sanguis. The procoagulant activity of the vegetations of these rabbits was also determined.The procoagulant activity of blood monocytes of rabbits with S. sanguis endocarditis was found to be similar to the activity of monocytes of rabbits with sterile vegetations, both at the time of isolation and after stimulation in vitro by exposure to endotoxin or phagocytosis of bacteria. The procoagulant activity of infected vegetations was significantly higher than that of sterile vegetations. We conclude that in bacterial endocarditis the coagulation system is activated locally at the site of the vegetation. Triggering probably occurs by thromboplastin generated by monocytes activated by phagocytosis of bacteria on the vegetational surface.
Revision Microvascular Decompression for Trigeminal Neuralgia and Hemifacial Spasm: Factors Associated with Surgical Failure
Authors: Ravina Kristine , Strickland Ben , Rennert Robert , Bakhsheshian Joshua , Russin Jonathan , Giannotta Steven 
Published: June 2018

Objective To investigate risk factors for symptom recurrence in patients requiring a revision microvascular decompression (MVD) for trigeminal neuralgia (TN) or hemifacial spasm (HFS).
Design Retrospective review of a prospectively maintained database.
Participants Seventeen consecutive patients undergoing revision MVD at our institution between January 1993 and September 2017.
Main Outcome Measures The incidence and causes for revision MVDs were recorded. Response to revision MVD for TN was tracked using the Barrow Neurological Institute (BNI) grading scale. Response to revision MVD for HFS was graded as “no improvement,” “some relief,” or “complete resolution” of symptoms.
Results Revision MVD rate for the senior author across all MVDs performed in this period was 1.9% for TN and 9.3% for HFS. Initial MVD failure was primarily caused by active inflammation and/or scarring and adhesions in 5/17 patients, malposition/slippage of Teflon in 3/17 patients, and insufficient Teflon in 1/17 patients. Without other factors, a new site of neurovascular conflict was identified in 4/17 patients, while the same site of neurovascular conflict was found in 3/17 patients. No cause could be identified in 1/17 patients. Scarring was found primarily in the TN group and was associated with symptom persistence.
Conclusion Revision MVD for recurrent TN and HFS is an effective procedure offering the prospect of a complete cure. Proper Teflon use is crucial for surgical success. Scarring after initial MVD is a negative prognostic factor requiring destructive treatment consideration. Although morbidity rates were slightly increased with revision versus original MVDs, the complications were non-disabling and resolved over time.
A Neonate with Exaggerated Startle and Tonic Spasms
Authors: Keshavan Shivan , Peruri Guruprasad , Suthar Renu , Angurana Suresh Kumar , Saini Lokesh , Sahu Jitendra 
Published: June 2018

AbstractHyperekplexia is a rare, potentially treatable inherited disorder of glycinergic neurotransmission, which is characterized by neonatal onset exaggerated startle response to somatosensory, auditory stimuli, and episodic tonic spasm. Prolonged tonic spasms can be life-threatening and associated with apnea and bradycardia. Awareness about this condition avoids misdiagnosis such as tonic seizures and epilepsy. We describe a term newborn with episodic tonic stiffness mistaken for seizures. Classical exaggerated startle reaction, positive head retraction response to glabellar tap, and characteristic video electroencephalogram confirmed the diagnosis.
Corrosion–microstructure interrelations in new low-lead and lead-free brass alloys
Authors: Stålnacke Emil , Claesson Erik , Obitz Charlotta , Lilja Mirjam , Odqvist Joakim , Hagström Joacim , Rod Olivier 
Published: June 2018

Stress-relieving heat treatment has been reported to deplete the corrosion resistance of new low-lead and lead-free brass alloys. How the heat treatment, processing and material composition relates to the microstructure and corrosion performance is not well understood. The present study aims to fill this knowledge gap by mapping stress-relieving annealing conditions and different standardised compositions to their respective microstructures and dezincification performance. It was found that loss of corrosion resistance was only the most severe for alloys with higher aluminium and iron content. These alloys displayed significant precipitation of intermetallic aluminium arsenide particles on grain boundaries, twins and lead particles, as well as the formation of β-phase along grain boundaries. This paper is part of a Thematic Issue on Copper and its Alloys.
Estimation of yttrium oxide microstructural parameters using the Williamson–Hall analysis
Authors: Emil Elif , Gürmen Sebahattin 
Published: June 2018

Yttrium oxide (Y2O3) particles were synthesised from a yttrium nitrate solution via ultrasonic spray pyrolysis (USP) method. The effects of temperature and precursor concentration on morphology and microstructural parameters were investigated. Y2O3 particles were characterised by scanning-electron-microscope energy-dispersive spectroscopy, Raman spectroscopy and X-ray diffraction analysis. Based on X-ray peak broadening, the crystallite size was calculated using the modified Debye–Scherrer (MDS) method. Furthermore, the crystallite size, crystal strain and the energy density of the crystal were evaluated using the Williamson–Hall (W–H) analysis integrated with the uniform deformation model, the uniform stress deformation model and the uniform deformation energy density model. A comparative evaluation of Y2O3 crystallite size using the MDS and W–H methods was carried out. This is part of a thematic issue on Nanoscale Materials Characterisation and Modeling by Advances Microscopy Methods - EUROMAT.
Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies
Authors: Harada Naoki 
Published: June 2018

ABSTRACTTestosterone is a sex hormone produced by testicular Leydig cells in males. Blood testosterone concentrations increase at three time-periods in male life–fetal, neonatal (which can be separated into newborn and infant periods), and pubertal stages. After peaking in the early 20s, the blood bioactive testosterone level declines by 1–2% each year. It is increasingly apparent that a low testosterone level impairs general physical and mental health in men. Here, this review summarizes recent systematic reviews and meta-analyses of epidemiological studies in males (including cross-sectional, longitudinal, and androgen deprivation studies, and randomized controlled testosterone replacement trials) in relation to testosterone and obesity, body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity. Furthermore, underlying mechanisms are discussed using data from rodent studies involving castration or androgen receptor knockout. This review provides an update understanding of the role of testosterone in energy metabolism.Abbreviations AR: androgen receptor; CV: cardiovascular; FDA: US Food and Drug Administration; HFD: high-fat diet; KO: knockout; MetS: metabolic syndrome; RCT: randomized controlled trial; SHBG: sex hormone binding globulin; SRMA: systematic review and meta-analysis; TRT: testosterone replacement therapy; T2DM:type 2 diabetes mellitus
An overview of anal intraepithelial neoplasia
Authors: Buzard Corina L. , Rizzolo Denise 
Published: June 2018

ABSTRACT
Anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC) are on the rise in the United States, especially among men who have sex with men, HIV-positive or other immunocompromised patients, and women with a history of cervical, vaginal, or vulvar cancer. Strong evidence supports the human papillomavirus as the causative factor in anal dysplasia; reducing the risk of HPV infection can reduce rates of ASCC. High-risk patients should be screened for AIN, but no universal screening guidelines exist, and more studies are needed to develop a national protocol for screening and management of patients with AIN.
Nonprescription Treatments are an Option for Many Women with Postmenopausal Vulvovaginal Symptoms
Authors: Rosenberg Karen 
Published: June 2018

According to this study:

Active treatment with either vaginal estradiol tablets or vaginal moisturizer provided no additional benefit over placebo in women with postmenopausal vulvovaginal symptoms.Many women can be treated with a nonprescription vaginal lubricating gel.
Sensitivity to Melody, Rhythm, and Beat in Supporting Speech-in-Noise Perception in Young Adults
Authors: Yates Kathryn M. , Moore David R. , Amitay Sygal , Barry Johanna G. 
Published: June 2018

Objectives:
Musicians appear to have an enhanced ability to perceive speech-in-noise, prompting suggestions that musical training could be used to help people who struggle to communicate in noisy environments. This study assessed the role of sensitivity to beat, rhythm, and melody in supporting speech-in-noise perception.

Design:
This is an exploratory study based on correlation. The study included 24 normally hearing young adult participants with a wide range of musical training and experience. Formal and informal musical experience was measured with the training subscale of the Goldsmiths’ Musical Sophistication Index. Speech reception thresholds (SRT) were measured using the Matrix Sentence Test and three different speech-spectrum-shaped noise maskers: unmodulated and sinusoidally amplitude-modulated (modulation frequency, f
m = 8 Hz; modulation depths: 60 and 80%). Primary predictors were measures of sensitivity to beat, rhythm, and melody. Secondary predictors were pure-tone frequency discrimination and auditory working memory (digit span). Any contributions from these two predictors were to be controlled for as appropriate.

Results:
Participants with more musical experience and greater sensitivity to rhythm, beat, and melody had better SRTs. Sensitivity to beat was more strongly linked with SRT than sensitivity to either rhythm or melody. This relationship remained strong even after factoring out contributions from frequency discrimination and auditory working memory.

Conclusions:
Sensitivity to beat predicted SRTs in unmodulated and modulated noise. We propose that this sensitivity maximizes benefit from fluctuations in signal-to-noise ratio through temporal orienting of attention to perceptually salient parts of the signal. Beat perception may be a good candidate for targeted training aimed at enhancing speech perception when listening in noise.
The diagnostic work-up of cancer-associated myositis
Authors: Selva-O’Callaghan Albert , Martinez-Gómez Xavier , Trallero-Araguás Ernesto , Pinal-Fernández Iago 
Published: June 2018

Purpose of review
Despite the well-recognized association between malignancy and myositis, definite data indicating the best strategy for diagnosing cancer in myositis patients is lacking. In this article, we review the data on cancer screening in patients with myositis, and propose an algorithm for this purpose based on recently published data.

Recent findings
Evidence has recently emerged supporting blind screening in patients with certain myositis phenotypes. In addition to the clinical examination, imaging techniques such as PET/computed tomography scanning and whole-body MRI, and determination of the autoantibody profile beyond anti-TIF1γ antibody, the well known cancer biomarker in dermatomyositis, will help the clinician face this complex clinical situation. Molecules related to the checkpoint inhibitor pathway, specifically soluble programmed death 1, may also have a role in the diagnostic work-up of cancer in myositis. In the future, blood tests analysing circulating DNA will certainly help in detecting patients with cancer-associated myositis (CAM).

Summary
A step forward has been achieved in the pathway to establish optimal cancer screening for myositis patients. International consensus guidelines for an effective diagnostic work-up of CAM are in progress and will be of paramount importance to improving the outcome in these patients.