Oxidative Mechanisms in Neurodegenerative Disorders. Proceedings from a satellite symposium, Guilin, China, 7-11 February 2004

This special issue of Molecular Neurobiology presents a series of mini-reviews resulting from an ISN satellite symposium entitled Oxidative Mechanisms in Neurodegenerative Disorders Held at the Guilin Park Hotel, Guilin, China on February 7-11, 2004. The timely topics in this symposium were contributed by more than 20 internationally acclaimed scientists and attended by more than 100 participants interested in this subject matter. This satellite symposium was also part of the 6th Biennial Asian-Pacific Society for Neurochemistry (APSN) meeting held in Hong Kong, China. Organizers included Dr. Piu Chan (Capital University of Medical Sciences and Beijing Institute of Geriatrics) Dr. Albert Y. Sun and Dr. Grace Y. Sun (University of Missouri, Columbia, MO). The satellite meeting was hosted by Xuanwu Hospital of Capital University of Medical Sciences and Guilin Medical College, and was generously supported by the following: the International Society of Neurochemistry (ISN), National Institutes of Health (USA) (1 R13 NS047414), the Geriatric Research, Education and Clinical Center (GRECC) VA Medical Center, Minneapolis, MN, USA, The Chinese Society of Neuroscience, Chinese Medical Association, Chinese Journal of Neurology, Shanghai Roche Pharmaceuticals Ltd., and Beijing QuiXave United Technology Ltd. Corporation.     

External electrical cardioversion of persistent atrial fibrillation in a patient with a Micra™ Transcatheter Pacing System

We report a case of a 85-year old woman with a preexisting Transcatheter Pacing System (TPS) (Micra? VR, Fa. Medtronic, Inc., Minneapolis, MN, USA) undergoing several external electrical cardioversions (CV) for symptomatic persistent atrial fibrillation (persAF). Due to bradycardia in the setting of atrial fibrillation a right apical TPS implantation was performed earlier. Four weeks prior to presentation at our facility an unsuccessful CV with a maximum biphasic energy level of 360J was performed, after which amiodarone was initiated. At the time of presentation three shocks with 100?J, 200?J and 360?J were delivered without sustained restoration of a stable sinus rhythm. Patches were in an anterior-posterior position. No complications and no significant changes in device parameters in comparison to the pre-acquired values were observed.To our knowledge, this is the first case report of an external CV in a patient with a TPS. External CV in patients with a preexisting TPS seems to be safe and feasible.     

Retrieval of a Micra transcatheter pacing system in a heart with a preexisting lead

We report the case of a 74-year-old man with a previously implanted pacemaker lead. He had undergone Medtronic? Micra Transcatheter Pacing System (TPS, Medtronic plc, MN, USA) implantation because of lead fracture. We implanted a new TPS and retrieved the dislodged one. We used a multiple-loop snare (EN snare^®) and an 8.5F steerable sheath (Agilis NXT; St. Jude Medical, St Paul, MN, USA). The TPS was obstructed by the chordae tendineae of the tricuspid valve and the pacemaker lead. We pushed the TPS to the apex site; this enabled us to move the TPS away from the chordae tendineae and pacemaker lead. The TPS body was caught in the inferior vena cava and was successfully retrieved. To our knowledge, this is the first case reporting TPS retrieval in a heart with preexisting lead.     

Ranavirus: past, present and future

Emerging infectious diseases are a significant threat to global biodiversity. While historically overlooked, a group of iridoviruses in the genus Ranavirus has been responsible for die-offs in captive and wild amphibian, reptile and fish populations around the globe over the past two decades. In order to share contemporary information on ranaviruses and identify critical research directions, the First International Symposium on Ranaviruses was held in July 2011 in Minneapolis, MN, USA. Twenty-three scientists and veterinarians from nine countries examined the ecology and evolution of ranavirus-host interactions, potential reservoirs, transmission dynamics, as well as immunological and histopathological responses to infection. In addition, speakers discussed possible mechanisms for die-offs, and conservation strategies to control outbreaks.     

Intrinsic anti-tachycardia pacing terminated ventricular tachycardia resistant to traditional anti-tachycardia pacing

Implantable cardioverter-defibrillators (ICDs) serve to reduce the risk of sudden death; however, ICD shocks worsen patient prognosis. Therefore, attempts have been made to terminate life-threatening arrhythmias without ICD shocks. A 71-year-old man with non-ischemic cardiomyopathy, who previously underwent cardiac resynchronization therapy-defibrillator (CRT-D) placement, was hospitalized for ventricular tachyarrhythmia (VT) that was refractory to traditional anti-tachycardia pacing (ATP). Endocardial and epicardial ablation failed to prevent VT recurrence. Since the CRT-D battery was exhausted, it was replaced with a Cobalt? XT HF CRT-D (Medtronic, Minneapolis, MN, USA), and the intrinsic ATP (iATP) algorithm was employed. Although VT recurred frequently, recurrent VTs were terminated by the iATP, which created a conduction block in the circuit without VT acceleration or shock. This is the first reported case wherein an iATP algorithm was effective against VT resistant to traditional anti-tachycardia pacing. This novel ATP algorithm has the potential to terminate refractory VT without ICD shocks and provide a better prognosis.     

Usefulness of a lead delivery system consisting of a fixed-shaped sheath and a lumenless bipolar lead in a patient with absent right and persistent left superior vena cava: A case report

We report the case of an 84-year-old female with symptomatic bradycardia due to a complete atrioventricular block, who carried absent right and persistent left superior vena cava (SVC). Implantation of a pacing lead, particularly within the right ventricle (RV) in a patient with this venous anomaly is accompanied by technical difficulties. However, the apparatus consisting of a fixed-curve sheath (Model C315-S10, Medtronic, Inc., Minneapolis, MN, USA) and a lumenless fixed-screw pacing lead (Model 3830, Medtronic), allowed a rapid delivery into the RV without any complications. By rotating the Model C315-S10 sheath in the counterclockwise direction in the right atrium, its tip faced the tricuspid orifice, advanced across the tricuspid valve and confronted the RV lower septum near the apex. Then the RV-lead was fixed with acceptable pacing and sensing parameters. Utilizing a lumenless pacing lead and a preformed sheath to deliver it is a novel approach that could be helpful in pacemaker implantation in patients with absent right and persistent left SVC.     

Bone marrow stromal cell-derived vascular endothelial growth factor (VEGF) rather than chronic lymphocytic leukemia (CLL) cell-derived VEGF is essential for the apoptotic resistance of cultured CLL cells

Chronic lymphocytic leukemia (CLL) cells feature a pronounced apoptotic resistance. The vascular endothelial growth factor (VEGF) possesses a role in this apoptotic block, although underlying functional mechanisms and the involvement of the microenvironment are unclear. In this study, the VEGF status in CLL was assessed by enzyme-linked immunosorbent assay and immunofluorescence. VEGF receptor 2 (VEGFR2) phosphorylation was determined flow cytometrically and by immunofluorescence. For co-culture, CLL cells were cultivated on a monolayer of the bone marrow-derived stromal cell (BMSC) line HS5. Secreted VEGF was neutralized using the monoclonal antibody mAb293 (R&D Systems, Minneapolis, MN, USA). To block protein secretion, we used Brefeldin A. VEGF was downregulated in BMSCs by small interfering RNA (siRNA), and we assessed survival by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. CLL cells express and secrete VEGF and possess phosphorylated VEGFR2. This positive VEGF status is not sufficient to prevent spontaneous apoptosis in vitro. Coculture with BMSCs, which secrete vast amounts of VEGF, maintains in vitro CLL cell survival. Blockage of secreted VEGF using the monoclonal antibody mAb293 significantly reduced the survival support for cocultured CLL cells. Both general blockage of protein secretion by Brefeldin A in BMSCs, but not in CLL cells, and siRNA-mediated downregulation of VEGF in BMSCs, significantly reduced the coculture-mediated survival support for CLL cells. It can be concluded that BMSC-derived proteins and VEGF, in particular, but not CLL cell-derived VEGF, is essentially involved in the coculture-mediated survival support for CLL cells. Hence, therapeutic targeting of VEGF signaling might be a promising approach to overcome the apoptotic resistance CLL cells feature within their natural microenvironment.     

Margaret C. Etter (Wilmington,DE: September 12, 1943 – Minneapolis,MN: June 10, 1992)

In Memoriam

Margaret C. Etter (Wilmington, DE: September 12, 1943 – Minneapolis, MN: June 10, 1992)     

Genetic control of invasive fish: technological options and its role in integrated pest management

Genetic options for the control of invasive fishes were recently reviewed and synthesized at a 2010 international symposium, held in Minneapolis/St. Paul, MN, USA. The only option currently available “off-the-shelf” is triploidy, which can be used to produce sterile males for a release program analogous to those widely and successfully used for biological control of insect pests. However, the Trojan Y and several recombinant options that heritably distort pest population sex ratios are technologically feasible, are at or are close to proof-of-concept stage and are potentially much more effective than sterile male release programs. All genetic options at this stage require prolonged stocking programs to be effective, though gene drive systems are a potential for recombinant approaches. They are also likely to differ in their current degree of social acceptability, with chromosomal approaches (triploidy and Trojan Y) likely to be the most readily acceptable to the public and least likely to require changes in legislative or policy settings to be implemented. Modelling also suggests that the efficacy of any of these genetic techniques is enhanced by, and in turn non-additively enhance, conventional methods of pest fish control.     

Successful termination of ventricular tachycardia with intrinsic anti-tachycardia pacing

Intrinsic anti-tachycardia pacing (iATP) is a novel automated ATP algorithm that employs post-pacing interval (PPI) to design the next ATP sequence based on an analysis of the prior failed ATP sequence. A patient with hypertrophic cardiomyopathy received an implantable cardioverter-defibrillator (ICD) (Cobalt™ XT DR, Medtronic, Minneapolis, MN, USA) following an episode of syncope due to macro-reentrant ventricular tachycardia (VT) (right bundle branch block configuration, cycle length [CL] 280 ms). The VF zone was set to VTCL <300 ms and iATP therapy was prescribed before and during capacitor charging. The iATP was initiated when VT recurred 3 months later. The first attempt with an assumption of 150 ms propagation time from the pacing site to the VT circuit (9 pulses) could not reset the VT, leaving a PPI of 650 ms. A subsequent attempt involving 20 pulses with an assumption of 250 ms propagation time terminated the VT. Failure to reach the circuit is a major cause of unsuccessful ATP. In this regard, iATP is expected to have theoretical advantages over empirical and traditional ATP therapies. To the best of our knowledge, this is the first intracardiac electrogram illustrating how automated precision ATP terminates VT in a clinical setting.     

Quantification of gender specific thermal sensory and pain threshold before and after laser needle stimulation]

Quantitative thermal sensory and pain threshold testing (QST) was performed in 29 adult healthy volunteers (mean age 24.2 +/- 2.7 years; range: 18-29 years; 20 females, 9 males) using the Thermal Sensory Analyser TSA-II (Medoc Advanced Medical Systems, Ramat Yishai, Israel, and Minneapolis, Minnesota, USA) before and after laser needle acupuncture and placebo stimulation, respectively. Significant (p < or = 0,001; t-test) gender-specific differences were seen on cold pain threshold analysis. No significant changes in parameters of thermal sensory and pain thresholds were found before and after laser needle or placebo stimulation at acupuncture points for acute pain. However, a trend towards change in the median value of cold pain sensation after laser needle stimulation (p = 0.479; paired t-test; n.s.) was seen within the group of healthy females. The influence of stimulation of acupuncture points for chronic pain on the various parameters needs to be clarified in future studies.     

Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. Autoantibodies against M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), which mainly belong to the IgG4 subclass, were reported as associated antibodies for the development of MN. Although PLA2R is a major target antigen for idiopathic MN, the prevalence of MN patients seropositive for PLA2R in Japan is lower than that in other countries. In this study, we conducted immunohistochemical analysis of the presence of THSD7A and PLA2R in renal specimens of MN patients to estimate the prevalence of THSD7A/PLA2R-related idiopathic MN in Japan. Enhanced granular expression of THSD7A and PLA2R was detected in 9.1% and 52.7%, respectively, of the patients with idiopathic MN. Although none of patients with secondary MN displayed enhanced granular expression of THSD7A, 5.4% of them had enhanced granular expression of PLA2R. In conclusion, the prevalence of enhanced granular expression of THSD7A in the glomeruli of Japanese patients with idiopathic MN was higher than the prevalence of MN patients seropositive for THSD7A in USA and Europe.     

Macroinvertebrate grazers,current velocity,and bedload transport rate influence periphytic accrual in a field-scale experimental stream

Periphyton plays an important role in stream ecology, and can be sensitive to macroinvertebrate grazers, near-bed current velocity, and bedload abrasion. We manipulated conditions to examine influences on periphytic accrual in the St. Anthony Falls Laboratory Outdoor StreamLab in Minneapolis, MN, USA. Macroinvertebrate grazers were excluded from 27 of 65 clay tiles using electric pulses. We examined periphytic biomass accrual as a function of grazer presence, sampling run, and near-bed current velocity using ANCOVA. We found significant temporal differences between sampling runs but no significant effect of grazer presence. Along with a strong association between bedload transport rates and mean periphytic biomass, our results suggest that grazers are relatively unimportant in stream systems with high levels of physical disturbance from floods and associated sand bedload. However, the interaction between grazer presence and velocity was marginally significant. Regression analyses showed no relation between velocity and periphyton in the absence of grazers but a negative relation when grazers were present, suggesting that mechanical dislodgement of periphyton by grazers may increase with velocity. We conclude that grazers can have subtle effects on periphyton, particularly in streams with high bedload transport rates.     

Transposon technology and vertebrate functional genomics

A report on the Third Annual International Conference on Transposition and Animal Biotechnology, Minneapolis, USA, 23-24 June 2005, and the FASEB Summer Research Conference 'Mammalian Mobile Elements', Tuscon, USA, 4-9 June, 2005.     

<Emphasis Type="Italic">N</Emphasis>-Acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation

We evaluated the effect of the antioxidant N-acetyl-l-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after ¹³¹I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post-¹³¹I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.     

Implications of climate change for North American wood warblers (Parulidae)

Since 1912, Neotropical–Nearctic migrant birds may now have up to 20 fewer days to travel between Southern Illinois, where spring is arriving later, and Northern Minnesota, where spring is arriving earlier, to exploit optimal habitat conditions (expanding leaves and caterpillar activity) for refueling and breeding. As case studies of the effect of climate change on bird migration, I analyzed two long‐term data sets of arrival times for eight species of northern breeding migratory wood warblers (Parulidae) gathered over a 100 year period in east‐central Illinois (IL, USA) and a 40 year period in western Minnesota (MN, USA). Six (IL) and seven (MN) of the wood warbler species showed no significant tendency to migrate earlier in response to earlier springs in their breeding range. These results suggest that climate change may force many species of long‐distance migratory songbirds to become uncoupled in the spring from their food resources that are driven by temperature.     

A disease transmission model in a nonconstant population

A general SIRS disease transmission model is formulated under assumptions that the size of the population varies, the incidence rate is nonlinear, and the recovered (removed) class may also be directly reinfected. For a class of incidence functions it is shown that the model has no periodic solutions. By contrast, for a particular incidence function, a combination of analytical and numerical techniques are used to show that (for some parameters) periodic solutions can arise through homoclinic loops or saddle connections and disappear through Hopf bifurcations.Supported in part by NSERC grant A-8965, the University of Victoria Committee on Faculty Research & Travel, and the Institute for Mathematics and its Applications, Minneapolis, MN, with funds provided by NSF     

Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus

Pulsed-field gel electrophoresis (PFGE) clonal type USA200 is the most widely disseminated Staphylococcus aureus colonizer of the nose and is a major cause of toxic shock syndrome (TSS). Exoproteins derived from these organisms have been suggested to contribute to their colonization and causation of human diseases but have not been well-characterized. Two representative S. aureus USA200 isolates, MNPE (α-toxin positive) and CDC587 (α-toxin mutant), isolated from pulmonary post-influenza TSS and menstrual vaginal TSS, respectively, were evaluated. Biochemical, immunobiological, and cell-based assays, including mass spectrometry, were used to identify key exoproteins derived from the strains that are responsible for proinflammatory and cytotoxic activity on human vaginal epithelial cells. Exoproteins associated with virulence were produced by both strains, and cytolysins (α-toxin and γ-toxin), superantigens, and proteases were identified as the major exoproteins, which caused epithelial cell inflammation and cytotoxicity. Exoprotein fractions from MNPE were more proinflammatory and cytotoxic than those from CDC587 due to high concentrations of α-toxin. CDC587 produced a small amount of α-toxin, despite the presence of a stop codon (TAG) at codon 113. Additional exotoxin identification studies of USA200 strain [S. aureus MN8 (α-toxin mutant)] confirmed that MN8 also produced low levels of α-toxin despite the same stop codon. The differences observed in virulence factor profiles of two USA200 strains provide insight into environmental factors that select for specific virulence factors. Cytolysins, superantigens, and proteases were identified as potential targets, where toxin neutralization may prevent or diminish epithelial damage associated with S. aureus.     

Possible role of the micronucleus assay in diagnostics and secondary prevention of cervix cancer: A minireview

Recent literature data are presented concerning micronuclei (MN) frequency in exfoliated cells of cervix cancer patients. These data strongly support a positive correlation between the MN level and malignization (changes from pre-malignant stage to cancer). It is suggested that the evaluation of frequency of MN in exfoliated cervical cells may be an additional criterion for establishing cervical cancer risk and the study of MN in cervix smears will increase the sensitivity and specificity of cytology which could impact in diagnostics and secondary prevention of cervical cancer. The text was submitted by the author in English.     

Effective dose and image quality for intraoperative imaging with a cone-beam CT and a mobile multi-slice CT in spinal surgery: A phantom study

PurposeTo compare the effective dose (ED) and image quality (IQ) of O-arm cone-beam CT (Medtronic, Minneapolis, MN, USA) and Airo multi-slice CT (Brainlab AG, Munich, Germany) for intraoperative-CT (i-CT) in spinal surgery.MethodsThe manufacturer-defined protocols available in the O-arm and Airo systems for three-dimensional lumbar spine imaging were compared.Organ dose was measured both with thermo-luminescent dosimeters and GafChromic films in the Alderson Radiation Therapy anthropomorphic phantom.A subjective analysis was performed by neurosurgeons to compare the clinical IQ of the anthropomorphic phantom images acquired with the different i-CT systems and imaging protocols.Image uniformity, noise, contrast-to-noise-ratio (CNR), and spatial resolution were additionally assessed with the Catphan 504 phantom.ResultsO-arm i-CT caused 56% larger ED than Airo due to the high definition (HD) imaging protocol.The noise was larger for O-arm images leading to a lower CNR than that measured for Airo. Moreover, scattering and beam hardening effects were observed in the O-arm images. Better spatial resolution was measured for the O-arm system (9 lp/cm) than for Airo (4 lp/cm).For all the investigated protocols, O-arm was found to be better for identifying anatomical features important for accurate pedicle screw positioning.ConclusionsAccording to phantom measurements, the HD protocol of O-arm offered better clinical IQ than Airo but larger ED. The larger noise of O-arm images did not compromise the clinical IQ while the superior spatial resolution of this system allowed a better visibility of anatomical features important for pedicle screw positioning in the lumbar region.