Adenoviral nerve growth factor and β-galactosidase transfer to spinal cord: a behavioral and histological analysis

1999 ◽  
Vol 90 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Nicholas M. Boulis ◽  
Vikas Bhatia ◽  
Theodore I. Brindle ◽  
Harland T. Holman ◽  
Daniel J. Krauss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Nerve Growth Factor ◽  
Viral Gene Expression ◽  
Adenoviral Vectors ◽  
Viral Gene ◽  
Content Type ◽  
Transgenic Expression ◽  
Spinal Cord Function ◽  
Fine Print

Object. The present study characterizes the time course and loci of gene expression induced by the administration of adenoviral vectors into spinal cord. Although a marked inflammatory response to these vectors occurred, no effect on spinal cord function was seen in the 1st postoperative week. The expression of transgenic genes delivered by viral vectors is being exploited throughout the nervous system. The present study utilized adenoviral vectors containing the Rous sarcoma virus (RSV) promoter and a nuclear localization signal to achieve transgenic expression in mammalian spinal cord. Methods. Initial experiments utilizing the vector Ad.RSVlacZ (1012 particles/ml) injected into the region of the central canal resulted in viral gene expression stretching over approximately 1.2 cm of spinal cord. Gene expression was first detected 3 days following viral administration and lasted until postinjection Day 14 with peak expression at Day 7. A variety of cell types in both white and gray matter expressed lacZ. Transgenic expression of the neurotrophin nerve growth factor (NGF) was achieved using injections of Ad.RSVNGF. On histological examination mononuclear inflammatory infiltrate and gliosis were revealed surrounding the injection sites of spinal cords receiving adenovirus but not vehicle. To assess spinal cord function during viral gene expression, animals previously trained in an operant runway task were tested at 7 days postinjection (the peak of viral gene expression) and demonstrated no changes in spinal cord function. Conclusions. Results of this study using adenoviral neurotrophic gene transfer indicate that it provided an effective tool for the delivery of potentially therapeutic proteins to the injured or diseased spinal cord.

scholarly journals Transcription Profile and Genomic Variations of Oryctes Rhinoceros Nudivirus in Coconut Rhinoceros Beetles

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Kayvan Etebari ◽  
Rhys Parry ◽  
Marie Joy B. Beltran ◽  
Michael J. Furlong
Keyword(s):  
Gene Expression ◽  
Southeast Asia ◽  
Pacific Islands ◽  
Biocontrol Agent ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Content Type ◽  
Oryctes Rhinoceros ◽  
Rhinoceros Beetle ◽  
The Pacific

ABSTRACT Oryctes rhinoceros nudivirus (OrNV) is a double-stranded DNA (dsDNA) virus which has been used as a biocontrol agent to suppress the coconut rhinoceros beetle (Oryctes rhinoceros) in Southeast Asia and the Pacific Islands. A new wave of O. rhinoceros incursions in Oceania is thought to be related to the presence of low-virulence isolates of OrNV or virus-tolerant haplotypes of beetles. In this study, chronically infected beetles were collected from Philippines, Fiji, Papua New Guinea (PNG), and the Solomon Islands (SI). RNA sequencing (RNA-seq) was performed to investigate the global viral gene expression profiles and for comparative genomic analysis of structural variations. Maximum likelihood phylogenic analysis indicated that OrNV strains from the SI and Philippines are closely related, while OrNV strains from PNG and Fiji formed a distinct adjacent clade. We detected several polymorphic sites with a frequency higher than 35% in 892 positions of the viral genome. Nonsynonymous mutations were detected in several hypothetical proteins and 15 nudivirus core genes, such as gp034, lef-8, lef-4, and vp91. We found limited evidence of variation in viral gene expression among geographic populations. Only a few genes, such as gp01, gp022, and gp107, were differentially expressed among different strains. Additionally, small RNA sequencing from the SI population suggested that OrNV is targeted by the host RNA interference (RNAi) response with abundant 21-nucleotide small RNAs. Some of these genomic changes are specific to the geographic population and could be related to particular phenotypic characteristics of the strain, such as viral pathogenicity or transmissibility, and this requires further investigation. IMPORTANCE Oryctes rhinoceros nudivirus has been an effective biocontrol agent against the coconut rhinoceros beetle in Southeast Asia and the Pacific Islands for decades. The recent outbreak of these beetles in many South Pacific islands has had a significant impact on livelihoods in the region. It has been suggested that the resurgence and spread of the pest are related to the presence of low-virulence isolates of OrNV or virus-tolerant haplotypes of beetles. We examined viral genomic and transcriptional variations in chronically infected beetles from different geographical populations. A high number of polymorphic sites among several geographical strains of OrNV were identified, but potentially only a few of these variations in the genome are involved in functional changes and can potentially alter the typical function. These findings provide valuable resources for future studies to improve our understanding of the OrNV genetic variations in different geographic regions and their potential link to virus pathogenicity.

Effect of vasodilators and myelotomy on recovery after acute spinal cord injury in rats

1979 ◽  
Vol 50 (3) ◽  
pp. 349-352 ◽  
Author(s):  
Alex S. Rivlin ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Quantitative Method ◽  
Cord Compression ◽  
Central Canal ◽  
Compression Injury ◽  
Dorsal Midline ◽  
Content Type ◽  
Cord Injury ◽  
Spinal Cord Function ◽  
Fine Print

✓ The effect of papaverine, nitroprusside, or myelotomy on the recovery of spinal cord function was studied in rats after acute cord-compression injury. Spinal cord recovery was measured by a quantitative method of clinical assessment previously developed in our laboratory. Neither papaverine nor nitroprusside improved recovery of cord function. Dorsal midline myelotomy extending anteriorly as far as the central canal did not produce significant improvement (p > 0.05). However, when the myelotomy extended completely through the cord in the anteroposterior plane significant improvement (p < 0.01) was obtained.

Reversible spinal cord trauma: a model for electrical monitoring of spinal cord function

1972 ◽  
Vol 36 (4) ◽  
pp. 402-406 ◽  
Author(s):  
Thomas J. Croft ◽  
Jerald S. Brodkey ◽  
Frank E. Nulsen
Keyword(s):  
Spinal Cord ◽  
Evoked Potentials ◽  
Sensitive Indicator ◽  
Spinal Cord Trauma ◽  
Content Type ◽  
Cortical Evoked Potentials ◽  
Spinal Cord Damage ◽  
Sensory Transmission ◽  
Spinal Cord Function ◽  
Fine Print

✓ Cortical evoked potentials in anesthetized cats were recorded by a noninvasive averaging technique as a means of estimating spinal cord damage. Graded pressure on the spinal cord produced reversible blocking of these potentials. With this type of trauma, block of motor transmission through the cord paralleled the block of sensory transmission, and each seemed to be a sensitive indicator of spinal cord function. The possible use of such monitoring in anesthetized patients undergoing spinal operations is discussed.

Chemotherapy as the initial treatment of spinal cord compression due to disseminated neuroblastoma

1989 ◽  
Vol 70 (5) ◽  
pp. 688-690 ◽  
Author(s):  
I. R. Sanderson ◽  
Jon Pritchard ◽  
Henry T. Marsh
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Initial Treatment ◽  
Cord Compression ◽  
Response To Treatment ◽  
Trial Period ◽  
Content Type ◽  
Sick Children ◽  
Spinal Cord Function ◽  
Fine Print

✓ During a 12-month trial period, all children attending the Hospitals for Sick Children, London, England, for management of spinal cord compression due to disseminated neuroblastoma were given chemotherapy as initial treatment rather than radiotherapy or laminectomy. Response to treatment was evaluated by a neurosurgeon as well as by oncologists. Four children were treated in this way and all made a full recovery of spinal cord function.

Somatosensory evoked potential monitoring in anterior thoracic vertebrectomy

2000 ◽  
Vol 92 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Harel Deutsch ◽  
Marc Arginteanu ◽  
Karen Manhart ◽  
Noel Perin ◽  
Martin Camins ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vertebral Body ◽  
Evoked Potential ◽  
False Negative ◽  
False Negative Rate ◽  
Neurological Deterioration ◽  
Somatosensory Evoked Potential ◽  
Content Type ◽  
Spinal Cord Function ◽  
Fine Print

Object. Spine surgeons have used intraoperative cortical and subcortical somatosensory evoked potential (SSEP) monitoring to detect changes in spinal cord function when intraoperative procedures can be performed to prevent neurological deterioration. However, the reliability of SSEP monitoring as applied to anterior thoracic vertebral body resections has not been rigorously assessed. Methods. The authors retrospectively reviewed hospital charts and operating room records obtained between August 1993 and December 1998 and found that SSEP monitoring was used in 44 surgical procedures involving an anterior approach for thoracic vertebral body resections. There were no patients in whom SSEP changes did not return to baseline during the surgical procedure. Patients in four cases, despite their stable SSEP recordings throughout the procedure, were noted immediately postoperatively to have experienced significant neurological deterioration. The false-negative rate in SSEP monitoring was 9%. Sensitivity was determined to be 0%. Conclusions. It is important to recognize high false-negative rates and low sensitivity of SSEP monitoring when it is used to record spinal cord function during anterior approaches for thoracic vertebrectomies. The insensitivity of SSEPs for motor deterioration during anterior thoracic vertebrectomies is likely due to the limitation of SSEPs, which monitor only posterior column function whereas motor paths are conveyed in the anterior and anterolateral spinal cord. The authors believe that SSEPs can not be relied on to detect reversible spinal damage during anterior thoracic vertebrectomies.

Neuronal survival following remote adenovirus gene delivery

2002 ◽  
Vol 96 (2) ◽  
pp. 212-219 ◽  
Author(s):  
Nicholas M. Boulis ◽  
Danielle E. Turner ◽  
Michael J. Imperiale ◽  
Eva L. Feldman
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Sciatic Nerve ◽  
Gene Delivery ◽  
Motor Neuron ◽  
Dna Fragmentation ◽  
Neuronal Survival ◽  
Content Type ◽  
Neuron Density ◽  
Fine Print

Object. Virus-mediated central nervous system gene delivery is a promising means of treating traumatized tissue or degenerative diseases. In the present study, the authors examined gene expression and neuronal survival in the spinal cord after sciatic nerve administration of an adenovirus vector expressing a LacZ reporter gene. Methods. The time course of adenovirus gene expression, DNA fragmentation, and neuronal density were quantified in rat lumbar spinal cord by staining for β-galactosidase (β-Gal), terminal deoxynucleotidyl transferase, and cresyl violet after microinjection of either saline or the reporter virus into rat sciatic nerve. The expression of β-Gal following remote vector delivery peaked at 7 days and declined thereafter but was not accompanied by neuronal cell death, as measured by DNA fragmentation. No significant difference in spinal motor neuron density was detected between virus-treated and control rats at any time point examined. Although the spinal cords removed from rats treated with cyclosporine prior to adenovirus injection contained substantially more neurons staining for β-Gal at 7 days (67% of total neurons), the decay in the number of stained neurons was not paralleled by a decline in motor neuron density. Conclusions. The authors conclude that remote gene expression is suppressed by a noncytolytic process.

Cervical spinal cord delivery of a rabies G protein pseudotyped lentiviral vector in the SOD-1 transgenic mouse

2004 ◽  
Vol 1 (1) ◽  
pp. 128-136 ◽  
Author(s):  
Kiana Tanase ◽  
Qingshan Teng ◽  
Ajit A. Krishnaney ◽  
James K. Liu ◽  
Mary E. Garrity-Moses ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Transgenic Mice ◽  
Lentiviral Vector ◽  
Cervical Spinal Cord ◽  
Wild Type ◽  
Therapeutic Gene ◽  
Content Type ◽  
Fine Print

Object. Lentiviral vectors may constitute a vehicle for long-term therapeutic gene expression in the spinal cord. In amyotrophic lateral sclerosis, spinal cord sclerosis and altered axonal transport pose barriers to therapeutic gene distribution. In the present study the authors characterize gene expression distribution and the behavioral impact of the rabies G (RabG) protein pseudotyped lentiviral vector EIAV.LacZ through cervical spinal cord injection in control and Cu/Zn superoxide dismutase—1 (SOD-1) transgenic mice. Methods. Seven-week-old SOD-1 transgenic mice and their wild-type littermates underwent exposure of the cervicomedullary junction and microinjection of RabG.EIAV.LacZ or vehicle. The Basso-Beattie-Bresnahan locomotor score, grip strength meter, and Rotarod assays were used to assess the effects of disease progression, spinal cord microinjection, and lentiviral gene expression. Spinal cords were removed when the mice were in the terminal stage of the disease. The distribution of LacZ gene expression was histologically evaluated and quantified. Direct cervical spinal cord microinjection of RabG.EIAV.LacZ results in extensive central nervous system uptake in SOD-1 transgenic mice; these findings were statistically similar to those in wild-type mice (p > 0.05). Gene expression lasts for the duration of the animal's survival (132 days). The SOD-1 mutation does not prevent retrograde axonal transport of the vector. Three behavioral assays were used to demonstrate that long-term gene expression does not alter sensorimotor function. In comparison with normative data, vector injection and transgene expression do not accelerate disease progression. Conclusions. Direct spinal cord injection of RabG.EIAV vectors represents a feasible method for delivering therapeutic genes to upper cervical spinal cord and brainstem motor neurons. Distribution is not affected by the SOD-1 mutation or disease phenotype.

scholarly journals ArabidopsisHistone Reader EMSY-LIKE 1 Binds H3K36 and Suppresses Geminivirus Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Tami Coursey ◽  
Milica Milutinovic ◽  
Elizabeth Regedanz ◽  
Jelena Brkljacic ◽  
David M. Bisaro
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Posttranslational Modifications ◽  
Chromatin Structure ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
In Planta ◽  
Pol Ii ◽  
Content Type ◽  
Active Gene

ABSTRACTHistone posttranslational modifications (PTMs) impart information that regulates chromatin structure and activity. Their effects are mediated by histone reader proteins that bind specific PTMs to modify chromatin and/or recruit appropriate effectors to alter the chromatin landscape. Despite their crucial juxtaposition between information and functional outcome, relatively few plant histone readers have been identified, and nothing is known about their impact on viral chromatin and pathogenesis. We used the geminivirusCabbage leaf curl virus(CaLCuV) as a model to functionally characterize two recently identified reader proteins, EMSY-LIKE 1 (EML1) and EML3, which contain Tudor-like Agenet domains predictive of histone PTM binding function. Here, we show that mutantArabidopsisplants exhibit contrasting hypersusceptible (eml1) and tolerant (eml3) responses to CaLCuV infection and that EML1 deficiency correlates with RNA polymerase II (Pol II) enrichment on viral chromatin and upregulated viral gene expression. Consistent with reader activity, EML1 and EML3 associate with nucleosomes and with CaLCuV chromatin, suggesting a direct impact on pathogenesis. We also demonstrate that EML1 and EML3 bind peptides containing histone H3 lysine 36 (H3K36), a PTM usually associated with active gene expression. The interaction encompasses multiple H3K36 PTMs, including methylation and acetylation, suggesting nuanced regulation. Furthermore, EML1 and EML3 associate with similar regions of viral chromatin, implying possible competition between the two readers. Regions of EML1 and EML3 association correlate with sites of trimethylated H3K36 (H3K36me3) enrichment, consistent with regulation of geminivirus chromatin by direct EML targeting.IMPORTANCEHistone PTMs convey information that regulates chromatin compaction and DNA accessibility. Histone reader proteins bind specific PTMs and translate their effects by modifying chromatin and/or by recruiting effectors that alter chromatin structure or activity. In this study, CaLCuV was used to characterize the activities of twoArabidopsisAgenet domain histone readers, EML1 and EML3. We show thateml1mutants are hypersusceptible to CaLCuV, whereaseml3plants are more tolerant of infection than wild-type plants. We also demonstrate that EML1 and EML3 associate with histones and viral chromatinin plantaand that both proteins bind peptides containing H3K36, a PTM associated with active gene expression. Consistent with antiviral activity, EML1 suppresses CaLCuV gene expression and reduces Pol II access to viral chromatin. By linking EML1 and EML3 to pathogenesis, these studies have expanded our knowledge of histone reader proteins and uncovered an additional level of viral chromatin regulation.

Safety and efficacy of stereotactic radiosurgery for tumors of the spine

2004 ◽  
pp. 413-418 ◽  
Author(s):  
Deborah L. Benzil ◽  
Mehran Saboori ◽  
Alon Y. Mogilner ◽  
Ronald Rocchio ◽  
Chitti R. Moorthy
Keyword(s):  
Spinal Cord ◽  
Single Dose ◽  
Pain Relief ◽  
Total Dose ◽  
Stereotactic Radiosurgery ◽  
Medical Center ◽  
Primary Tumors ◽  
Content Type ◽  
Increased Risk ◽  
Fine Print

Object. The extension of stereotactic radiosurgery treatment of tumors of the spine has the potential to benefit many patients. As in the early days of cranial stereotactic radiosurgery, however, dose-related efficacy and toxicity are not well understood. The authors report their initial experience with stereotactic radiosurgery of the spine with attention to dose, efficacy, and toxicity. Methods. All patients who underwent stereotactic radiosurgery of the spine were treated using the Novalis unit at Westchester Medical Center between December 2001 and January 2004 are included in a database consisting of demographics on disease, dose, outcome, and complications. A total of 31 patients (12 men, 19 women; mean age 61 years, median age 63 years) received treatment for 35 tumors. Tumor types included 26 metastases (12 lung, nine breast, five other) and nine primary tumors (four intradural, five extradural). Thoracic tumors were most common (17 metastases and four primary) followed by lumbar tumors (four metastases and four primary). Lesions were treated to the 85 to 90% isodose line with spinal cord doses being less than 50%. The dose per fraction and total dose were selected on the basis of previous treatment (particularly radiation exposure), size of lesion, and proximity to critical structures. Conclusions. Rapid and significant pain relief was achieved after stereotactic radiosurgery in 32 of 34 treated tumors. In patients treated for metastases, pain was relieved within 72 hours and remained reduced 3 months later. Pain relief was achieved with a single dose as low as 500 cGy. Spinal cord isodoses were less than 50% in all patients except those with intradural tumors (mean single dose to spinal cord 268 cGy and mean total dose to spinal cord 689 cGy). Two patients experienced transient radiculitis (both with a biological equivalent dose (BED) > 60 Gy). One patient who suffered multiple recurrences of a conus ependymoma had permanent neurological deterioration after initial improvement. Pathological evaluation of this lesion at surgery revealed radiation necrosis with some residual/recurrent tumor. No patient experienced other organ toxicity. Stereotactic radiosurgery of the spine is safe at the doses used and provides effective pain relief. In this study, BEDs greater than 60 Gy were associated with an increased risk of radiculitis.

Posterior approach for cervical intramedullary arteriovenous malformation with diffuse-type nidus

1999 ◽  
Vol 91 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Kenji Ohata ◽  
Toshihiro Takami ◽  
Alaa El-Naggar ◽  
Michiharu Morino ◽  
Akimasa Nishio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Poor Prognosis ◽  
Posterior Approach ◽  
The Other ◽  
Anterior Spinal Artery ◽  
Neural Element ◽  
Feeding Artery ◽  
Diffuse Type ◽  
Content Type ◽  
Fine Print

✓ The treatment of spinal intramedullary arteriovenous malformations (AVMs) with a diffuse-type nidus that contains a neural element poses different challenges compared with a glomus-type nidus. The surgical elimination of such lesions involves the risk of spinal cord ischemia that results from coagulation of the feeding artery that, at the same time, supplies cord parenchyma. However, based on evaluation of the risks involved in performing embolization, together with the frequent occurrence of reperfusion, which necessitates frequent reembolization, the authors consider surgery to be a one-stage solution to a disease that otherwise has a very poor prognosis. Magnetic resonance (MR) imaging revealed diffuse-type intramedullary AVMs in the cervical spinal cords of three patients who subsequently underwent surgery via the posterior approach. The AVM was supplied by the anterior spinal artery in one case and by both the anterior and posterior spinal arteries in the other two cases. In all three cases, a posterior median myelotomy was performed up to the vicinity of the anterior median fissure that divided the spinal cord together with the nidus, and the feeding artery was coagulated and severed at its origin from the anterior spinal artery. In the two cases in which the posterior spinal artery fed the AVM, the feeding artery was coagulated on the dorsal surface of the spinal cord. Neurological outcome improved in one patient and deteriorated slightly to mildly in the other two patients. Postoperative angiography demonstrated complete disappearance of the AVM in all cases. Because of the extremely poor prognosis of patients with spinal intramedullary AVMs, this surgical technique for the treatment of diffuse-type AVMs provides acceptable operative outcome. Surgical intervention should be considered when managing a patient with a diffuse-type intramedullary AVM in the cervical spinal cord.

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