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Biomedical subjects

A J Barton

Publications and source records attributed to A J Barton.

28 records · Page 2Linked to original sources

Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease.

Messenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

Adult↗

Expression of amyloid beta-protein precursor mRNAs in familial Alzheimer's disease.

The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimer's disease. The differential expression of APP transcripts may contribute to this process. In the present study, the distribution of mRNAs encoding APP variants has been determined in the brain of three cases of familial Alzheimer's disease (FAD) using in-situ hybridization histochemistry. One FAD case was associated with a mutation in the APP gene. No differences in distribution or quantity of APP transcripts were observed between FAD cases and controls. Overexpression of APP mRNAs is therefore an unlikely explanation for the deposition of the beta-amyloid (beta/A4) peptide in FAD brains.

Adult↗

Distribution of messenger RNAs encoding the enzymes glutaminase, aspartate aminotransferase and glutamic acid decarboxylase in rat brain.

In situ hybridization histochemistry (ISHH) using synthetic oligonucleotide probes has been used to identify cells containing the mRNAs coding for glutaminase (GluT), aspartate aminotransferase (AspT) and glutamic acid decarboxylase (GAD). The distribution of GAD mRNA confirms previous descriptions and matches the distribution of GAD detected using specific antibodies. AspT mRNA is widely distributed in the brain, but is present at high levels in GABAergic neuronal populations, some that may be glutamatergic, and in a subset of neurons which do not contain significant levels of either GAD or GluT mRNA. Particularly prominent are the neurons of the magnocellular division of the red nucleus, the large cells in the deep cerebellar nuclei and the vestibular nuclei and neurons of the lateral superior olivary nucleus. GluT mRNA does not appear to be present at high levels in all GAD-containing neurons, but is seen prominently in many neuronal populations that may use glutamate as a neurotransmitter, such as neocortical and hippocampal pyramidal cells, the granule cells of the cerebellum and neurons of the dentate gyrus of the hippocampus. The heaviest labelling of GluT mRNA is seen in the lateral reticular nucleus of the medulla. ISHH using probes directed against the mRNAs encoding these enzymes may be an important technique for identifying glutamate and aspartate using neuronal populations and for examining their regulation in a variety of experimental and pathological circumstances.

Animals↗

Distribution of a kainate/AMPA receptor mRNA in normal and Alzheimer brain.

In-situ hybridization (ISH) has been used to determine the distribution of the mRNA encoding a non-NMDA glutamatergic receptor subtype in rat and human brain. In the rat, signal is concentrated over neurons in hippocampus and cerebellum, with moderate labelling of neocortex and diencephalon. In human brain, a similar hippocampal and cerebellar distribution is seen, although with lower overall levels. Quantitative comparison between normal and Alzheimer's disease (AD) brain reveals a modest increase of this mRNA in AD subiculum and CA4 hippocampal field with no change in cerebellum. The significance of the increase is discussed in relation to other data suggesting glutamatergic involvement in AD.

Alzheimer Disease↗

Increased tau messenger RNA in Alzheimer's disease hippocampus.

The microtubule-associated protein tau is present in the pathologic hallmarks of Alzheimer's disease and its production and deposition have been implicated in the pathogenesis of the disease. We detected tau mRNA using in situ hybridization histochemistry in the hippocampus, visual cortex, and cerebellum, and compared its level in Alzheimer's disease with controls. The amount of tau mRNA also was determined as a ratio of total polyadenylated mRNA in each area. A significant and gene-specific increase in tau mRNA hybridization was found in hippocampal fields CA4 and CA3, with a similar trend in the dentate gyrus. In contrast, no change was found in the visual cortex or cerebellum in Alzheimer's disease. Increased hippocampal expression of tau mRNA also was present in cases of non-Alzheimer's dementia. Enhanced tau mRNA may be a marker of attempted plasticity involving the cytoskeleton in neuronal populations affected by various neurodegenerative disorders.

Aged↗

Messenger RNA encoding the D2 dopaminergic receptor detected by in situ hybridization histochemistry in rat brain.

A 30 base synthetic oligonucleotide probe was used to detect the mRNA encoding the rat D2 dopaminergic receptor. On Northern analysis, the probe identified a single species of mRNA of approximately 2.9 kb, present at highest levels in the striatum but also found in the brainstem, neocortex and diencephalon. On sections, neurons containing high levels of the mRNA were detected in the striatum, the substantia nigra pars compacta and the ventral tegmental area. Lower levels of signal were seen over neurons in the hypothalamus, the frontal neocortex, and the globus pallidus.

Animals↗

Clinical and economic outcomes of infants receiving breast milk in the NICU.

ISSUES AND PURPOSE: This study compared clinical and economic outcomes for infants who were exclusively fed breast milk and infants who were fed commercial formula. DESIGN AND METHODS: A retrospective medical record review from a regional neonatal intensive care unit (N = 80) using consultation logs from the lactation coordinator and a matched sample of formula-fed infants. RESULTS: Neither clinical (weight gain, length of stay, days of parenteral nutrition) nor economic outcomes (direct variable costs, net revenue) differed significantly between the groups. PRACTICE IMPLICATIONS: While it may not be possible to demonstrate sufficient cost savings while the infant resides within the NICU to justify a lactation coordinator, long-term clinical and economic outcomes may be sensitive to this specialized nursing service.

Cost Savings↗

Linking remote practice to research: technology in action.

Nursing faculty practices are rarely set up to collect and analyze data, but evidence about the effects and costs of clinical care provided by faculty is required by health plans and other payers. This article describes a strategy that links faculty research programs with practice and teaching activities in various locations. An informatics infrastructure uses a common language for data collection and a set of coherent processes for implementation. The theoretical basis for conducting practice-based research is explored.

Colorado↗