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Biomedical subjects

B T Harris

Publications and source records attributed to B T Harris.

14 recordsLinked to original sources

MRI study of immediate cell viability in focused ultrasound lesions in the rabbit brain.

The purpose of this study was to evaluate cell viability in MR imaged focused ultrasound (FUS) lesions using cell-viability staining with triphenyl tetrazolium chloride (TTC) and both light and electron microscopy. Ten paired ultrasonic lesions were created in 5 rabbit brains in vivo with an ultrasound beam of 1.5 MHz electrical power input to the transducer of 50 W and exposure duration of 15 seconds. T2-weighted fast spin-echo (FSE) MRI was performed to detect the FUS lesions in the brain 4 hours after treatment, after which the animals were immediately euthanized. Lesion sizes were measured on TTC-stained specimens, histological sections stained with hematoxylin and eosin (H&E), and T2-weighted MR images. The differences between the lesion diameters measured with the three methods were within the range of 0.1--0.7 mm. The lesion sizes measured from MRI correlated well with those seen from H&E sections. The measurements from MRI slightly overestimated lesion sizes on TTC-stained wet tissues by approximately one MRI pixel (0.31 mm). Electron microscopy demonstrated nuclear and cytoplasmic ultrastructural damage within the grey-white, non-TTC-stained lesion zone, whereas the TTC-stained normal tissue showed preservation of neuronal ultrastructure. Therefore, MR-imaged lesions represent a cell-death zone in rabbit brain 4 hours after FUS ablation, with slight overestimation by approximately one MRI pixel. J. Magn. Reson. Imaging 2001;13:23-30.

Animals↗

Spinal cord glioneuronal tumor with "rosetted" neuropil islands and meningeal dissemination: a case report.

Distinctive glioneuronal tumors arising within the cerebrum and displaying neuropil-like islands and tumor cells immunoreactive for neuronal and glial antigens have recently been described. We report a similar tumor in the cervico-thoracic region of the spinal cord in a 44-year-old woman that recurred 1 year later with dissemination to the lumbar dura and cauda equina. The tumor was composed of "rosetted" neuropil islands displaying immunoreactivity for synaptophysin, whereas the intervening tumor cells were more fibrillar and immunoreactive for GFAP. The tumor cell nuclei immediately surrounding these neuropil islands were immunoreactive to the newly characterized neuronal marker, anti-Hu. While several cases of neurocytomas have been described in the spinal cord, to the best of our knowledge, this is the first example of a glioneuronal tumor with "rosetted" neuropil islands to be reported in the spinal cord.

Adult↗

Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: an interesting case.

High grade gliomas foster an environment rich in angiogenic factors that promote neovascularity. We report a case of a cerebral arteriovenous malformation, which developed in the setting of a high grade astrocytoma. The patient presented with complaints of confusion and left hemiparesis. An initial cerebral angiogram was normal. Repeat angiography six weeks later demonstrated an extremely vascular lesion with arteriovenous shunting involving the right thalamus and occipital lobe. Histopathologic evaluation of open biopsy and autopsy specimens demonstrated a high grade astrocytoma in association with an arteriovenous malformation. Immunohistochemical staining with VEGF was diffusely positive. A possible role for the hyperangiogenic environment of a high grade astrocytoma resulting in the development of an arteriovenous malformation is discussed.

Astrocytoma↗

Melanotic craniopharyngioma: a report of two cases.

We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment. This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma. The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke's pouch epithelium.

Aged↗

Differentially expressed GABAA-receptor subunits result in structurally and functionally receptor assemblies following excitatory afferent synaptic transmission.

Cerebellar granule cells isolated from postnatal day 7 rat pups are ideal for studying epigenetic events associated with the regulation of neuronal gene expression. These cultures contain from 90 to 95% glutamatergic granule cells and express mRNAs encoding a variety of ionotropic and metabotropic glutamate receptors as well as virtually all of the GABAA-receptor subunit mRNAs to different extents. A unique feature of this culture system is that the neurons undergo time-dependent maturation changes in vitro that mimic many of the characteristics of these receptors occurring in vivo. Granule cell cultures in vitro require depolarizing concentrations of KCl for long-term growth and survival. Both N-methyl-D-aspartate (NMDA) and GABA have been reported to exert trophic actions on these cells replacing the requirement for maintaining the cultures in high KCl. Cerebellar granule cells maintained under different conditions in vitro can be induced to alter their patterns of maturation, as indicated by the different temporal changes in gene expression of receptor subunit mRNAs and proteins. The focus of the current studies is the effect of NMDA afferent synaptic signaling on the changes in mRNA content and functional properties of GABAA receptors and how this may relate to comparable changes shown to occur in vivo.

Animals↗

Exposure of neuronal cultures to K+ depolarization or to N-methyl-D-aspartate increases the transcription of genes encoding the alpha 1 and alpha 5 GABAA receptor subunits.

The transcription rates of the alpha 1, alpha 5, and alpha 6 gamma-aminobutyric acidA receptor subunit genes were analyzed in cultures maintained in low KCl (12.5 mM), in low KCl treated with NMDA (10 microM), and in high KCl (25 mM). alpha 1 and alpha 5 transcription rates were significantly increased in response to NMDA or high KCl treatment, while alpha 6 and cyclophilin transcription rates were not changed by either condition. These data suggest that following NMDA or high KCl treatment of granule cells, changes in alpha 1 and alpha 5 mRNA content are a consequence of a specific transcriptional rate increase of the corresponding subunit genes.

Animals↗

NMDA-mediated modulation of gamma-aminobutyric acid type A receptor function in cerebellar granule neurons.

GABAA receptors are ligand-gated CI- ion channels with multiple clinically relevant drug-recognition sites. We have previously shown that stimulation of N-methyl-D-aspartic acid (NMDA)-specific glutamate receptors quantitatively alters selected GABAA receptor subunit mRNAs and proteins in primary cultures of rat cerebellar granule neurons. We used whole-cell recordings of GABA-elicited CI- currents and flunitrazepam binding experiments in granule cell cultures maintained in low K+ (12.5 mM), cells maintained in low K+ and treated with a single dose of NMDA (10 microM), and cell cultures maintained in depolarizing concentrations of K+ (25 mM). The EC50 obtained from the dose-response curves for GABA in eliciting a maximal response was comparable in neurons maintained in high K+ or in low K+ and treated with a single dose of NMDA, but that it increased significantly in cells maintained in low K+. The potentiation of GABA-gated CI- currents by flunitrazepam increased significantly, while the negative allosteric modulator methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) was significantly more effective in cultures either maintained in high K+ or treated with NMDA. This was coincident with a twofold increase in the Bmax associated with flunitrazepam binding. To further characterize the receptor assemblies present in the depolarization and NMDA induced paradigms, the Zn(2+)-induced inhibition of GABA-gated CI- currents was reduced as was the inhibition mediated by furosemide. Our data indicate that GABAA receptor assemblies alter their composition in response to excitatory afferent receptor stimulation.

Animals↗

Quantitative changes in alpha 1 and alpha 5 gamma-aminobutyric acid type A receptor subunit mRNAs and proteins after a single treatment of cerebellar granule neurons with N-methyl-D-aspartate.

It was previously demonstrated that daily administration of N-methyl-D-aspartate (NMDA) to primary cultures of cerebellar granule neurons for 5 days in vitro mediates an increase in the relative content of mRNAs encoding selected subunits of the gamma-aminobutyric acid (GABA)A receptor. This analysis was extended using a competitive polymerase chain reaction assay with internal standards to quantitate changes that occur in the absolute amounts of selected GABAA receptor subunit mRNAs in cerebellar granule neurons in vitro after the single administration of nontoxic doses of either NMDA or glutamate. For these studies, we focused on the alpha 1, alpha 5, and alpha 6 receptor subunit mRNAs and examined their absolute contents in cultures maintained in low KCl (12.5 mM), maintained in low KCl and treated with NMDA (10 microM) for 24 hr, or maintained in high KCl (25 mM). The absolute amounts of each mRNA varied in these paradigms; whereas the alpha 1 and alpha 5 receptor subunit mRNAs increased in response to NMDA-selective glutamate receptor stimulation, the alpha 6 receptor subunit mRNA did not. The time course of the alpha 1 and alpha 5 mRNA increases, dose dependence, and effects of glutamate in the presence or absence of MK-801 were also analyzed. Treatment of cultures maintained in 12.5 mM KCl with 5 microM glutamate resulted in comparable changes in the alpha 1 and alpha 5 receptor subunit mRNA contents, and a somewhat smaller increase in the alpha 6 mRNA content was observed. Using corresponding GABAA receptor subunit-specific antibodies, it was shown that the observed mRNA changes are accompanied by increased expression of alpha 1- and alpha 5-like receptor subunit immunoreactivity. Collectively, these data demonstrate that signal transduction mechanisms triggered by NMDA-selective glutamate receptor stimulation differentially modulate the levels of selected GABAA receptor subunit mRNAs and the corresponding proteins they encode.

Amino Acid Sequence↗

The quality of diabetic care in a London health district.

In order to assess the quality of care in a community-wide sample of diabetic patients, a study was performed on 217 such patients identified in three group practices in an east London health district. Only 46% of the patients were currently attending a hospital. In the two years before review, 64% of patients had had their blood pressure recorded and 59% had had retinal examinations. Levels of glycosylated haemoglobin were significantly higher in patients on insulin than in those on oral regimes (P = 0.0004). The mean level of glycosylated haemoglobin was higher in patients from Social Classes III, IV, and V than in patients from Social Classes I and II (P = 0.005), but there was no difference in level between those patients attending hospital and those attending their general practitioners after accounting for differences in these two populations (P = 0.19). Over 50% of all diabetic patients in this study had levels of glycosylated haemoglobin which may indicate vulnerability to microvascular disease.

Catchment Area, Health↗

A pilot Diabetic Support Service based on family practice attenders: comparison with diabetic clinics in east London.

A pilot Diabetic Support Service (DSS) based on a computer register was devised for diabetic patients identified within three group practices in an inner city district of London. Of 159 eligible diabetics, 142 were followed over 2 years. Glycosylated haemoglobin (GHb) monitoring and adequacy of clinic reviews were audited. Care achieved by the DSS was compared with conventional Diabetic Clinic (DC) management of a sample of 200 diabetics from the same district. Serial GHb measurements were made on 66.2% of DSS and 44.5% of DC patients: GHb fell significantly only in DSS patients (13.1% to 11.4%). Proportional falls in GHb were comparable in each DSS treatment group (diet alone, oral hypoglycaemic agents, and insulin) and for hospital attenders and non-attenders equally. The planned clinical reviews were achieved in 40.1% of DSS patients entered (29% GP only, 54% of clinic attenders) and in 15% of DC patients (plus 75% fundal and blood pressure examination). The study led to provision of a formal diabetic clinic annual review system, diabetic mini-clinics in two of the three group practices, and the appointment of two Diabetic Liaison Sisters. With administrative simplification the system is to be made available to all diabetics in the District through their GPs during 1986-8.

Adult↗