Biomedical subjects

Stephen Hearn

Publications and source records attributed to Stephen Hearn.

6 recordsLinked to original sources

PubMed2005

A primate virus generates transformed human cells by fusion.

Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

Animals↗

PubMed2005

Regulating gene expression through RNA nuclear retention.

Multiple mechanisms have evolved to regulate the eukaryotic genome. We have identified CTN-RNA, a mouse tissue-specific approximately 8 kb nuclear-retained poly(A)+ RNA that regulates the level of its protein-coding partner. CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage. CTN-RNA is diffusely distributed in nuclei and is also localized to paraspeckles. The 3'UTR of CTN-RNA contains elements for adenosine-to-inosine editing, involved in its nuclear retention. Interestingly, knockdown of CTN-RNA also downregulates mCAT2 mRNA. Under stress, CTN-RNA is posttranscriptionally cleaved to produce protein-coding mCAT2 mRNA. Our findings reveal a role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress. This mechanism of action highlights an important paradigm for the role of a nuclear-retained stable RNA transcript in regulating gene expression.

3' Untranslated Regions↗

PubMed2005

Use of a motorized bicycle exercise trainer to normalize frequency-dependent habituation of the H-reflex in spinal cord injury.

BACKGROUND/OBJECTIVES: Spasticity in patients with spinal cord injury (SCI) is difficult to manage. Exercise and stretching is advocated as a management tool, but these activities are difficult to perform for most patients as a result of multiple barriers. This report shows the effect of passive range-of-motion exercise in a walking-like pattern on frequency-dependent habituation of the H-reflex in the lower extremities of an individual with spastic tetraplegia due to SCI. METHODS: The participant, a man with a chronic ASIA B C7 SCI due to a gunshot wound, used a motorized bicycle exercise trainer (MBET) developed at the Jackson T. Stephens Spine & Neurosciences Institute at the University of Arkansas for Medical Sciences that could be operated from the individual's wheelchair. He used the MBET for 1 hour, 5 days a week, for 13 weeks. H-reflex habituation was tested at the beginning of the study and then periodically over the course of 17 weeks, including 4 weeks after exercise had ceased. RESULTS: Significant habituation of the H-reflex was evident beginning at the 10th week of training. The habituation in the H-reflex reached a normal level at 5- and 10-Hz frequencies at 12 weeks. Subjective assessment of spasticity indicated that it was significantly reduced. The H-reflex amplitude was maintained at normal levels during the remaining week of the course of exercise and for 2 additional weeks after exercise ceased. The H-reflex habituation, however, returned to near baseline when reassessed at week 17, 4 weeks after the exercise program had concluded. Subjective assessment indicated that spasticity also had returned to pretraining levels. CONCLUSIONS: Habituation of the H-reflex, and perhaps spasticity, can be managed by a routine passive range-of-motion exercise program using a MBET, but the exercise program may need to be continuous. The benefit of reduced medication for spasticity and possibly improved quality of life could be a motivating factor for an individual with SCI and spasticity to continue the program. Because of the low complexity of the program, ease of use, and small size, this system could be inexpensive and could be used by an individual in the home. Ongoing studies will determine the minimum amount of MBET training required for maintaining long-term H-reflex habituation.

Adult↗

PubMed2004

Tissue-specific expression and dynamic organization of SR splicing factors in Arabidopsis.

The organization of the pre-mRNA splicing machinery has been extensively studied in mammalian and yeast cells and far less is known in living plant cells and different cell types of an intact organism. Here, we report on the expression, organization, and dynamics of pre-mRNA splicing factors (SR33, SR1/atSRp34, and atSRp30) under control of their endogenous promoters in Arabidopsis. Distinct tissue-specific expression patterns were observed, and differences in the distribution of these proteins within nuclei of different cell types were identified. These factors localized in a cell type-dependent speckled pattern as well as being diffusely distributed throughout the nucleoplasm. Electron microscopic analysis has revealed that these speckles correspond to interchromatin granule clusters. Time-lapse microscopy revealed that speckles move within a constrained nuclear space, and their organization is altered during the cell cycle. Fluorescence recovery after photobleaching analysis revealed a rapid exchange rate of splicing factors in nuclear speckles. The dynamic organization of plant speckles is closely related to the transcriptional activity of the cells. The organization and dynamic behavior of speckles in Arabidopsis cell nuclei provides significant insight into understanding the functional compartmentalization of the nucleus and its relationship to chromatin organization within various cell types of a single organism.

Arabidopsis↗

PubMed2002

A reliable primary human CNS culture protocol for morphological studies of dendritic and synaptic elements.

Primary dissociated human fetal forebrain cultures were grown in defined serum-free conditions. At 4 weeks in vitro the cultures contained abundant morphologically well differentiated neurons with complex dendritic arbors. Astrocytic proliferation was negligible without the use of antimitotic agents. Confocal scanning laser microscopy (CSLM) and electron microscopy confirmed the presence of a dense neuropil, numerous cell-cell contacts and synapses. Neurons expressed a variety of proteins including growth associated protein-43 (GAP43), microtubule associated protein-2ab (MAP), class-III beta tubulin (C3BT), neurofilaments (NF), synaptophysin (SYN), parvalbumin (PA) and calbindin (CB). The cultures have proven to be reliable and simple to initiate and maintain for many weeks without passaging. They are useful in investigations of dendritic growth and injury of primary human CNS neurons.

Calbindins↗

PubMed2002

Mechanical ventilation of isolated rat lungs changes the structure and biophysical properties of surfactant.

Mechanical ventilation is an essential but potentially harmful therapeutic intervention for patients with acute lung injury. The objective of this study was to investigate the effects of mechanical ventilation on large-aggregate surfactant (LA) structure and function. Isolated rat lungs were randomized to either a nonventilated control group, a relatively noninjuriously ventilated group [1 h, 10 ml/kg tidal volume, 3 cmH(2)O positive end-expiratory pressure (PEEP)], or an injuriously ventilated group (1 h, 20 ml/kg tidal volume, 0 cmH(2)O PEEP). Injurious ventilation resulted in significantly decreased lung compliance compared with the other two groups. LA structure, as determined by electron microscopy, revealed that LA from the injurious group had significantly lower amounts of organized lipid-protein structures compared with LA obtained from the other groups. Analysis of the biophysical properties by using a captive bubble surfactometer demonstrated that adsorption and surface tension reduction were significantly impaired with LA from the injuriously ventilated lungs. We conclude that the injurious mechanical ventilation impairs LA function and that this impairment is associated with significant morphological alterations.

Adsorption↗