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Biomedical subjects

Greg Allen

Publications and source records attributed to Greg Allen.

7 recordsLinked to original sources
PubMed2005

Neural stem cells express non-neural markers during embryoid body coculture.

The capacity of neural stem cells (NSC) to transdifferentiate into a wide range of non-neuronal lineages is the subject of debate. One approach to test NSC plasticity is to ectopically place NSCs in permissive or instructive microenvironments in which the signals driving differentiation of multiple cell types are being elicited. Here we produce embryoid body neurosphere aggregates by combining neurosphere derivatives from fetal mice constitutively expressing green fluorescent protein with embryonic stem (ES) cells isolated from Zin40 mice constitutively expressing nuclear beta-galacosidase. Under these conditions, we assess neurosphere-derivative-immunoreactivity to anti-neurofilament heavy chain, anti-pan-cytokeratin, anti-smooth muscle alpha-actinin and anti-alpha-fetoprotein-specific antibodies. Furthermore, we determine lineage-specific transgene expression and undertake fluorescence in situ hybridization to assess ES cell-neural stem cell-fusion indices. Our data demonstrate that following coculture in hanging drops with ES cells, neurosphere derivatives display immunoreactivity to non-neural markers, in particular smooth muscle, which is not dependent upon cell-cell fusion. These results suggest that given an appropriate environment, NSC may lose their in vivo restrictions and display non-neuronal phenotypes.

Animals↗
PubMed2005

Magnetic resonance imaging of cerebellar-prefrontal and cerebellar-parietal functional connectivity.

Recent studies of the cerebellum indicated its involvement in a diverse array of functions, and analyses of non-human primate neuroanatomy have revealed connections between cerebellum and cerebral cortex that might support cerebellar contributions to a wider range of functions than traditionally thought. These include cortico-ponto-cerebellar projections originating throughout cerebral cortex, in addition to projections from the dentate nucleus of the cerebellum to prefrontal and posterior parietal cortices via the thalamus. Such projections likely serve as important substrates for cerebellar involvement in human cognition, assuming their analogues are prominent in the human brain. These connections can be examined from a functional perspective through the use of functional connectivity MRI (FCMRI), a technique that allows the in vivo examination of coherence in MR signal among functionally related brain regions. Using this approach, low-frequency fluctuations in MR signal in the dentate nucleus correlated with signal fluctuations in cerebellar, thalamic, limbic, striatal, and cerebrocortical regions including parietal and frontal sites, with prominent coherence in dorsolateral prefrontal cortex. These findings indicate that FCMRI is a useful tool for examining functional relationships between the cerebellum and other brain regions, and they support the findings from non-human primate studies showing anatomic projections from cerebellum to regions of cerebral cortex with known involvement in higher cognitive functions. To our knowledge, this represents the first demonstration of functional coherence between the dentate nucleus and parietal and prefrontal cortices in the human brain, suggesting the presence of cerebellar-parietal and cerebellar-prefrontal functional connectivity.

Adult↗
PubMed2004

Cerebellar function in autism: functional magnetic resonance image activation during a simple motor task.

BACKGROUND: The cerebellum is one of the most consistent sites of neuroanatomic abnormality in autism, yet it is still unclear how such pathology impacts cerebellar function. In normal subjects, we previously demonstrated with functional magnetic resonance imaging (fMRI) a dissociation between cerebellar regions involved in attention and those involved in a simple motor task, with motor activation localized to the anterior cerebellum ipsilateral to the moving hand. The purpose of the present investigation was to examine activation in the cerebella of autistic patients and normal control subjects performing this motor task. METHODS: We studied eight autistic patients and eight matched normal subjects, using fMRI. An anatomic region-of-interest approach was used, allowing a detailed examination of cerebellar function. RESULTS: Autistic individuals showed significantly increased motor activation in the ipsilateral anterior cerebellar hemisphere relative to normal subjects, in addition to atypical activation in contralateral and posterior cerebellar regions. Moreover, increased activation was correlated with the degree of cerebellar structural abnormality. CONCLUSIONS: These findings strongly suggest dysfunction of the autistic cerebellum that is a reflection of cerebellar anatomic abnormality. This neurofunctional deficit might be a key contributor to the development of certain diagnostic features of autism (e.g., impaired communication and social interaction, restricted interests, and stereotyped behaviors).

Adolescent↗
PubMed2003

Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism.

OBJECTIVE: Recent years have seen a revolution in views regarding cerebellar function. New findings suggest that the cerebellum plays a role in multiple functional domains: cognitive, affective, and sensory as well as motor. These findings imply that developmental cerebellar pathology could play a role in certain nonmotor functional deficits, thereby calling for a broader investigation of the functional consequences of cerebellar pathology. Autism provides a useful model, since over 90% of autistic cerebella examined at autopsy have shown well-defined cerebellar anatomic abnormalities. The aim of the present study was to examine how such pathology ultimately impacts cognitive and motor function within the cerebellum. METHOD: Patterns of functional magnetic resonance imaging (fMRI) activation within anatomically defined cerebellar regions of interest were examined in eight autistic patients (ages 14-38 years) and eight matched healthy comparison subjects performing motor and attention tasks. For the motor task, subjects pressed a button at a comfortable pace, and activation was compared with a rest condition. For the attention task, visual stimuli were presented one at a time at fixation, and subjects pressed a button to every target. Activation was compared with passive visual stimulation. RESULTS: While performing these tasks, autistic individuals showed significantly greater cerebellar motor activation and significantly less cerebellar attention activation. CONCLUSIONS: These findings shed new light on the cerebellar role in attention deficits in autism and suggest that developmental cerebellar abnormality has differential functional implications for cognitive and motor systems.

Adolescent↗
PubMed2002

Benchmarking in emergency health systems.

This paper discusses the role of benchmarking as a component of quality management. It describes the historical background of benchmarking, its competitive origin and the requirement in today's health environment for a more collaborative approach. The classical 'functional and generic' types of benchmarking are discussed with a suggestion to adopt a different terminology that describes the purpose and practicalities of benchmarking. Benchmarking is not without risks. The consequence of inappropriate focus and the need for a balanced overview of process is explored. The competition that is intrinsic to benchmarking is questioned and the negative impact it may have on improvement strategies in poorly performing organizations is recognized. The difficulty in achieving cross-organizational validity in benchmarking is emphasized, as is the need to scrutinize benchmarking measures. The cost effectiveness of benchmarking projects is questioned and the concept of 'best value, best practice' in an environment of fixed resources is examined.

Benchmarking↗