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Jack Price

Publications and source records attributed to Jack Price.

18 recordsLinked to original sources
PubMed2025

Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.

Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.

Humans↗
PubMed2007

The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry.

The in vivo monitoring of cell survival and migration will be essential to the translation of cell-based therapies from the laboratory to clinical studies. The pre-labeling of cells with magnetic resonance imaging (MRI) contrast agents renders them visible in vivo for serial cellular imaging. However, little is known about the impact of the presence of these metal particles inside transplanted cells. The use of the bimodal contrast agent GRID made it possible to demonstrate by means of fluorescent microscopy and inductively coupled plasma mass spectrometry (ICP-MS) that, after 16 h of incubation (without the use of a transfection agent), neural stem cells (NSCs) were saturated and no longer incorporated particles. With this maximal uptake, no significant effect on cell viability was observed. However, a significant decrease in proliferation was evident in cells that underwent 24 h of labeling. A significant increase in reactive oxygen species was observed for all GRID labeling, with a very significant increase with 24 h of labeling. GRID labeling did not affect cell motility in comparison with PKH26-labeled NSCs in a glioma-based migration assay and also allowed differentiation into all major cell types of the brain. GRID-labeled cells induced a signal change of 47% on T(2) measurements and allows a detection of cell clusters of approximately 220 cells/microl. Further in vivo testing will be required to ensure that cell labeling with gadolinium-based MRI contrast agents does not impair their ability to repair.

Animals↗
PubMed2006

A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke.

Transplantation of neural stem cells into the brain is a novel approach to the treatment of chronic stroke disability. For clinical application, safety and efficacy of defined, stable cell lines produced under GMP conditions are required. To this end, a human neural stem cell line, CTX0E03, was derived from human somatic stem cells following genetic modification with a conditional immortalizing gene, c-mycER(TAM). This transgene generates a fusion protein that stimulates cell proliferation in the presence of a synthetic drug 4-hydroxy-tamoxifen (4-OHT). The cell line is clonal, expands rapidly in culture (doubling time 50-60 h) and has a normal human karyotype (46 XY). In the absence of growth factors and 4-OHT, the cells undergo growth arrest and differentiate into neurons and astrocytes. Transplantation of CTX0E03 in a rat model of stroke (MCAo) caused statistically significant improvements in both sensorimotor function and gross motor asymmetry at 6-12 weeks post-grafting. In addition, cell migration and long-term survival in vivo were not associated with significant cell proliferation. These data indicate that CTX0E03 has the appropriate biological and manufacturing characteristics necessary for development as a therapeutic cell line.

Analysis of Variance↗
PubMed2006

Rapid ventricular remodeling with left ventricular unloading postventricular assist device placement: new insights with strain imaging.

We report the case of a 6-year old girl who presented with severe dilated cardiomyopathy. Cross-sectional echocardiography demonstrated a severely dilated hypokinetic left ventricle with an ejection fraction less than 10%. She developed intractable ventricular tachyarrhythmias and subsequently had a left ventricular assist device implanted. Within 1 week of mechanical support, echocardiography demonstrated dramatic reverse remodeling of the left ventricle with marked improvement in myocardial deformation using strain rate imaging. This report further highlights the potential for rapid remodeling after mechanical support of the failing myocardium.

Cardiomyopathy, Dilated↗
PubMed2006

Author retraction.

Explore the source record for details and available documents.

Retraction Notice↗
PubMed2005

Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin.

In humans, neurotrauma is suspected to cause brain atrophy and accelerate slowly progressive neurodegenerative disorders, such as Alzheimer's disease or schizophrenia. However, a direct link between brain injury and subsequent delayed global neurodegeneration has remained elusive. Here we show that juvenile (4-week-old) mice that are given a discrete unilateral lesion of the parietal cortex, develop to adulthood without obvious clinical symptoms. However, when monitored 3 and 9 months after lesioning, using high-resolution three-dimensional MRI and behavioural testing, the same mice display global neurodegenerative changes. Surprisingly, erythropoietin, a haematopoietic growth factor with potent neuroprotective activity, prevents behavioural abnormalities, cognitive dysfunction and brain atrophy when given for 2 weeks after acute brain injury. This demonstrates that a localized brain lesion is a primary cause of delayed global neurodegeneration that can be efficiently counteracted by neuroprotection.

Acute Disease↗
PubMed2005

Expression of POU-domain transcription factor, Oct-6, in schizophrenia, bipolar disorder and major depression.

BACKGROUND: The POU-domain transcription factor Oct-6 has been reported to be differentially expressed between schizophrenic and control post-mortem brains. In this study, we attempted to replicate this finding and to discover whether Oct-6 was also dysregulated in bipolar disorder and major depression. METHODS: Oct-6 mRNA and protein expression were determined by in-situ hybridization and immunohistochemistry respectively in sections of post-mortem brain. RESULTS: We did not observe any differences in Oct-6 expression between any of the groups under study. Oct-6 mRNA and protein was identically expressed in the hippocampal and cortical regions of most specimens in all groups, including controls. CONCLUSION: Oct-6 is, therefore, unlikely to be a specific marker for any psychological disorder; rather its expression in controls suggests that it is normally expressed in most adult brains.

Adult↗
PubMed2005

Airborne emissions of mercury from municipal solid waste. I: new measurements from six operating landfills in Florida.

Mercury-bearing material enters municipal landfills from a wide array of sources, including fluorescent lights, batteries, electrical switches, thermometers, and general waste; however, the fate of mercury (Hg) in landfills has not been widely studied. Using automated flux chambers and downwind atmospheric sampling, we quantified the primary pathways of Hg vapor releases to the atmosphere at six municipal landfill operations in Florida. These pathways included landfill gas (LFG) releases from active vent systems, passive emissions from landfill surface covers, and emissions from daily activities at each working face (WF). We spiked the WF at two sites with known Hg sources; these were readily detected downwind, and were used to test our emission modeling approaches. Gaseous elemental mercury (Hg(O)) was released to the atmosphere at readily detectable rates from all sources measured; rates ranged from approximately 1-10 ng m(-2) hr(-1) over aged landfill cover, from approximately 8-20 mg/hr from LFG flares (LFG included Hg(O) at microg/m3 concentrations), and from approximately 200-400 mg/hr at the WF. These fluxes exceed our earlier published estimates. Attempts to identify specific Hg sources in excavated and sorted waste indicated few readily identifiable sources; because of effective mixing and diffusion of Hg(O), the entire waste mass acts as a source. We estimate that atmospheric Hg releases from municipal landfill operations in the state of Florida are on the order of 10-50 kg/yr, substantially larger than our original estimates, but still a small fraction of current overall anthropogenic losses.

Air Pollutants↗
PubMed2005

Airborne emissions of mercury from municipal solid waste. II: potential losses of airborne mercury before landfill.

Waste distribution and compaction at the working face of municipal waste landfills releases mercury vapor (Hg(o)) to the atmosphere, as does the flaring of landfill gas. Waste storage and processing before its addition to the landfill also has the potential to release Hg(o) to the air if it is initially present or formed by chemical reduction of Hg(II) to Hg(o) within collected waste. We measured the release of Hg vapor to the atmosphere during dumpster and transfer station activities and waste storage before landfilling at a municipal landfill operation in central Florida. We also quantified the potential contribution of specific Hg-bearing wastes, including mercury (Hg) thermometers and fluorescent bulbs, and searched for primary Hg sources in sorted wastes at three different landfills. Surprisingly large fluxes were estimated for Hg losses at transfer facilities (approximately 100 mg/hr) and from dumpsters in the field (approximately 30 mg/hr for 1000 dumpsters), suggesting that Hg emissions occurring before landfilling may constitute a significant fraction of the total emission from the disposal/landfill cycle and a need for more measurements on these sources. Reducing conditions of landfill burial were obviously not needed to generate strong Hg(o) signals, indicating that much of the Hg was already present in a metallic (Hg(o)) form. Attempts to identify specific Hg sources in excavated and sorted waste indicated few readily identifiable sources; because of effective mixing and diffusion of Hg(o), the entire waste mass acts as a source. Broken fluorescent bulbs and thermometers in dumpsters emitted Hg(o) at 10 to >100 microg/hr and continued to act as near constant sources for several days.

Air Pollutants↗
PubMed2004

Nestin expression is lost in a neural stem cell line through a mechanism involving the proteasome and Notch signalling.

Neural stem cells (NSCs) are believed to repair brain damage primarily through cell replacement: i.e., the ability to regenerate lost neurons and glia in a site-specific fashion. The neural stem cell line, MHP36, has been shown to have this capacity, but we have little idea of the molecular mechanisms that control the differentiation of such cells during brain repair. In this study we show that an early event in the differentiation of MHP36 cells, both in vivo and in vitro, is the loss of expression of the intermediate filament protein, nestin. We use a co-culture assay to show that loss of nestin is fast, being detectable after just 1 h and complete in 4 h, and is controlled by proteasome degradation rather than down-regulation of de novo nestin synthesis. We also show that nestin loss is regulated by Notch, and mediated by cell contact.

Acetylcysteine↗
PubMed2004

Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.

Preferential migration of stem cells toward the site of a lesion is a highly desirable property of stem cells that allows flexibility in the site of graft implantation in the damaged brain. In rats with unilateral stroke damage, neural stem cells transplanted into the contralateral hemisphere migrate across to the lesioned hemisphere and populate the area around the ischaemic infarct. To date, the migration of neural stem cells in the damaged brain has been mainly inferred from snapshot histological images. In this study, we demonstrate that by pre-labelling neural stem cells with the bimodal contrast agent Gadolinium-RhodamIne Dextran [GRID, detectable by both magnetic resonance imaging (MRI) and fluorescent microscopy], the transhemispheric migration of transplanted neural stem cells contralateral to a stroke lesion can be followed in vivo by serial MRI and corroborated by subsequent histological analyses. Our results indicate that neural stem cells migrated from the injection tract mainly along the corpus callosum within 7 days of transplantation and extensively re-populated the peri-lesion area by 14 days following implantation. In contrast, neural stem cells transplanted into sham controls did not show any substantial migration outside of the injection tract, suggesting that the transcallosal migration observed in the stroke-lesioned animals is due to neural stem cells being attracted by the lesion site. In vivo tracking of the migration of neural stem cells responding to damage will greatly enhance our understanding of optimal transplantation strategies as well as how neural stem cells promote functional and anatomical recovery in neurological disorders.

Animals↗
PubMed2003

Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy.

BACKGROUND: Left ventricular noncompaction (LVNC) is a reportedly uncommon genetic disorder of endocardial morphogenesis with a reportedly high mortality rate. The purpose of this study was to identify the clinical characteristics of children with LVNC. METHODS AND RESULTS: We retrospectively reviewed 36 children with LVNC evaluated at Texas Children's Hospital (TCH) from January 1997 to December 2002. Five children had associated cardiac lesions. There were 16 girls and 20 boys. The median age at presentation was 90 days (range, 1 day to 17 years). The median duration of follow-up was 3.2 years (range, 0.5 to 12 years). Twenty-seven patients (75%) had ECG abnormalities, most commonly biventricular hypertrophy (10 patients, 28%). Both ventricles were involved in 8 patients (22%) and only the left ventricle in 28 patients (78%). Left ventricular systolic function was depressed in 30 patients (83%), with a median ejection fraction of 30% (range, 15% to 66%) at diagnosis. Nine patients presenting in the first year of life with depressed left ventricular contractility had a transient recovery of function; however, ejection fraction deteriorated later in life, at a median interval of 6.3years (range, 3 to 12 years). Two patients had an "undulating" phenotype from dilated to hypertrophic cardiomyopathy. Two patients (6%) were identified with an underlying G4.5 gene mutation. Five patients (14%) died during the study. CONCLUSIONS: LVNC does not have an invariably fatal course when diagnosed in the neonatal period. A significant number of patients have transient recovery of function followed by later deterioration, which may account for many patients presenting as adults, some manifesting an "undulating" phenotype.

Acyltransferases↗
PubMed2003

Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way.

Aging↗
PubMed2002

Expression of Oct-6, a POU III domain transcription factor, in schizophrenia.

OBJECTIVE: Oct-6, a POU-III domain transcription factor, is expressed in embryonic stem cells and Schwann cells and in neuronal subpopulations during early mammalian development, but its relevance to disorders of cerebral development in humans is untested. This study evaluated the expression of Oct-6 in schizophrenia, a disorder that has been linked with neurodevelopmental abnormalities. METHOD: Immunohistochemistry was used to examine Oct-6 expression in the temporal lobe in postmortem tissue from 10 subjects with schizophrenia and 10 matched comparison subjects. Western blot analysis was used to study Oct-6 expression in the frontal and temporal cortex in tissue from an additional three schizophrenic and three matched comparison subjects and in the frontal lobe only in tissue from an additional 10 schizophrenic and 10 matched comparison subjects. RESULTS: Extensive Oct-6 immunoreactivity was present in the temporal lobe in all 10 schizophrenic subjects, while very little or no expression was found in the comparison subjects. In schizophrenic subjects, Oct-6 immunoreactivity was found in a subset of cells in the pyramidal cell layer of the hippocampus and in the granule cell layer of the dentate gyrus. Oct-6 staining was predominantly localized in the cytoplasm. Western blot analysis confirmed the presence of Oct-6 in the frontal and temporal cortex in schizophrenic subjects but not in comparison subjects. CONCLUSIONS: The presence of Oct-6 expression in the schizophrenic subjects but not in the comparison subjects suggests that Oct-6 may provide a marker for the neuropathology associated with schizophrenia. Further, it may provide a clue to the neurodevelopmental basis of the disease and could be a reliable means to examine the developmental brain abnormalities described in this disorder.

Adult↗
PubMed2002

Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging.

The ability to track stem cell transplants in the brain by in vivo neuroimaging will undoubtedly aid our understanding of how these cells mediate functional recovery after neural transplantation. One major challenge for the development and refinement of stem cell transplantation is to map the spatial distribution and rate of migration in situ. Here we report a method for tracking transplanted stem cells in the ischemia-damaged rat hippocampus by magnetic resonance imaging (MRI). Before transplantation, stem cells were labeled in vitro either with a novel bifunctional contrast agent, gadolinium rhodamine dextran (GRID), identifiable by both MRI and fluorescence microscopy, or with PKH26, visible exclusively under fluorescence microscopy. At different time points following engraftment, the brains were evaluated by both histology and ex vivo MR imaging. Transplanted stem cells were identified by MRI only if prelabeled with GRID, whereas fluorescence microscopy detected transplanted cells using either label. The distribution of GRID-labeled stem cells identified by MRI corresponded to those detected using fluorescence microscopy. These results demonstrate that GRID-enhanced MRI can reliably identify transplanted stem cells and their migration in the brain.

Animals↗