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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 163 records · Page 9Linked to original sources
PubMed1997

An immunohistochemical and morphometric study on astrocytes and microvasculature in the human cerebral cortex.

In this study, astrocytes and microvessels of the human cerebral cortex were analysed morphometrically with the aim of acquiring quantitative information on the glio-vascular relationships, considered to be of great importance in the formation and functioning of the blood-brain barrier. Immunohistochemistry for the astrocytic marker, glial fibrillary acidic protein, was used with a computerized image analysis system. The brain tissue was embedded using the progressive lowering of temperature method, and the image analyser was applied to semithin sections subjected to immunogold-silver staining and viewed by epipolarization microscopy. The results show that, in the human cerebral cortex, astrocytes cover 11.4% of the cortex area and that their perivascular processes are nearly as extensive as the vascular bed (0.8% versus 1.72% of the cortex area). These processes form a virtually continuous sheath around the vascular walls, only 11% of the vessel perimeter lacking this astrocytic glia covering. The present results, compared with previous unpublished data obtained by conventional immunocytochemical procedures on wax sections, indicate that low-temperature methods combined with gold-silver immunolabelling on semithin sections significantly improve the detection of immunoreactivity and the performance of the image analyser.

Astrocytes↗
PubMed1997

Gene-based neurotransmitter modulation in cerebellar granule neurons.

The human glutamic acid decarboxylase (GAD) gene was transferred into rat cerebellar granule neurons. Following adenoviral-mediated gene transfer, nearly 100% of the neurons had transgene expression that persisted for the duration of their survival in culture. GABA levels were elevated both in the growth media and in lysates of GAD-modified granule neurons. In GAD-modified neurons, extracellular GABA levels steadily increased with time, whereas intracellular GABA levels peaked 10 days after gene transfer. GAD-modified neurons released both glutamate and GABA into the surrounding media before and after potassium-induced stimulation, but only the release of glutamate was sensitive to potassium stimulation. These data suggest that glutamatergic neurons, which initially contained no detectable GABA, can be genetically modified to release GABA constitutively.

Adenoviridae↗
PubMed1997

Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices.

Whole cell voltage-clamp recordings were performed on auditory olivocochlear neurons in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of norepinephrine (NE; 1-10 microM) reversibly induced an inward current in 26 of 38 labeled neurons that were voltage clamped at -75 mV. This was responsible for the membrane depolarization to NE observed in current-clamp mode. The NE-induced inward current appeared to be more prominent at -55 mV than at -75 mV and reversed at around -100 mV. It was attenuated but not prevented by 20 mM tetraethylammonium, and it persisted when the perfusate contained 2 mM Cs+ or 100 microM Cd2+. However, the NE-induced inward current was attenuated to varying degrees in a zero-Ca2+ solution. Current-voltage plots revealed that NE caused a decrease in membrane K+ conductance. A suppression of voltage-gated Ca2+ currents by NE was also observed. The excitatory action of NE was blocked by the alpha-adrenoreceptor antagonist phentolamine. The alpha1-adrenoreceptor agonist phenylephrine had an effect similar to that of NE. In 6 of 38 labeled neurons, an inhibitory action of NE (1-10 microM) was observed that appeared to be due to an activation of an inwardly rectified K+ current, which caused hyperpolarization of resting membrane potentials in current-clamp mode. This inhibitory response was independent of external Ca2+ and was abolished by 2-5 mM Cs+ or 0.5 mM Ba2+ applied in the perfusate. The receptors involved in the inhibitory actions of NE are not clear. The effect was partially and reversibly blocked by propranolol (10 microM), a beta-adrenoreceptor antagonist. However, isoprenaline (10 microM), a beta-adrenoreceptor agonist, failed to induce any effect. On the other hand, the inhibitory effect was irreversibly blocked by pretreatment with phentolamine (5-10 microM). Phenylephrine (5-10 microM) had no effect.

Animals↗
PubMed1997

Malignant vagotonia due to selective baroreflex failure.

Baroreflex failure is characterized by dramatic fluctuations of sympathetic activity and paroxysms of hypertension and tachycardia. In contrast, unopposed parasympathetic activity has not been described in patients with baroreflex failure because of concurrent parasympathetic denervation of the heart. We describe the unusual case of a patient with baroreflex failure in a setting of preserved parasympathetic control of HR manifesting episodes of severe bradycardia and asystole. Thus, parasympathetic control of the HR may be intact in occasional patients with baroreflex failure. Patients with this selective baroreflex failure require a unique therapeutic strategy for the control of disease manifestations.

Baroreflex↗
PubMed1997

Adult-onset focal dystonias: presentation and treatment options.

Adult-onset focal dystonias (AFD) are common disorders that are often misdiagnosed and incorrectly treated. Their presentation is readily recognized, and botulinum toxin has become the agent of choice for treating these disorders. Most of the focal dystonias include cervical dystonia, blepharospasm, oromandibular dystonia, spasmodic dysphonia, and limb dystonia, specifically writer's cramp. Their onset is either idiopathic, familial, or post-traumatic, and the pathophysiology of the focal dystonias is not currently known. Local injections of botulinum toxin into the affected area result in chemical denervation of the muscle, resulting in a weakness of the muscles that are involved in the sustained contractions. This weakness alleviates the painful contraction of the dystonia. In this paper we present a case study of the most common type of focal dystonia, cervical dystonia. The etiology in this case was post-traumatic, and significant improvement resulted after treatment with botulinum toxin type A.

Botulinum Toxins, Type A↗
PubMed1997

The role of clinical pharmacology in molecular genetics.

PROBLEM: Discovering the causes of unusual phenotypes in human subjects is an important aspect of patient-oriented research. MATERIAL: The tools of clinical pharmacology are uniquely useful in addressing these problems. PATIENTS, SUBJECTS, OR CASE HISTORIES: We evaluated a 42-year-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and pharmacological tests outlined in this article. RESULTS: These studies indicated that sympathetic innervation was intact but that the sympathetic neurotransmitter was dopamine rather than norepinephrine. These results demonstrated that dopamine-beta-hydroxylase deficiency underlies the clinical abnormalities of this patient. CONCLUSION: In selected individuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almost the resolution of the human genome.

Adult↗
PubMed1997

The physiological conundrum of hyperadrenergic orthostatic intolerance.

Orthostatic hypotension is a well-recognized medical problem in patients whose blood pressure falls dramatically with standing. Much less recognized is the syndrome of orthostatic intolerance. In patients with orthostatic intolerance, there are symptoms evoked by standing, but little actual fall in blood pressure. On the other hand, orthostatic intolerance patients frequently have a brisk tachycardia on standing. It has recently been recognized that many such individuals have a mild dysautonomia which may be brought on by conditions such as an antecedent viral illness, a rheumatologic disorder, or surgery/anesthesia. Recent studies of the hyperadrenergic (elevated plasma norepinephrine) subgroup of orthostatic intolerance is documenting a clinical spectrum including attenuated plasma renin activity and aldosterone, reduced supine blood volume coupled with dynamic orthostatic hypovolemia, elevated plasma norepinephrine and epinephrine, impaired clearance of norepinephrine from the circulation and evidence of partial dysautonomia. The emergence of partial dysautonomia as an important mechanism of orthostatic intolerance may lead to a substantial alteration in therapeutic approach.

Autonomic Nervous System↗
PubMed1997

Glucose transporter GLUT1 in human brain microvessels revealed by ultrastructural immunocytochemistry.

The brain glucose transporter GLUT1 is a transmembrane glycoprotein belonging to the glucose carrier family comprising five isoforms characterized by different functional properties and tissue specificity. Biochemical and immunohistochemical analyses have demonstrated that GLUT isoform 1 is localised within the brain microvascular endothelium, where it controls glucose uptake through the blood-brain barrier (BBB). In this study the expression of GLUT1 was analysed by means of light and electron immunocytochemistry in the adult human cerebellar cortex. The glucose transporter is strongly expressed in cerebellum microvessels, and is localised not only within endothelial cells but also in microvascular pericytes. Moreover, some glial expression of GLUT1 was observed in the neutrophil and in perivascular glial sheaths. The observations demonstrate that different cellular types are involved in the control of brain glucose homeostasis by GLUT1 expression at the BBB site, and support the postulated highly specialised role of brain microvascular pericytes.

Adult↗
PubMed1997

Evaluation and treatment of uncompensated unilateral vestibular disease.

This article reviews the general literature regarding the clinical evaluation and treatment of a unilateral vestibular deficit. The clinical approach by the authors is highlighted with a focus on bedside examinations and cyclodeviation measurements. Vestibular rehabilitation is currently considered the best approach to rehabilitation at present, and its physiologic basis is reviewed. When applied early in the course of recovery, vestibular rehabilitation can hasten compensation and also reduce symptoms resulting from permanent deficits caused by vestibular injury.

Humans↗
PubMed1996

Central noradrenergic lesioning using anti-DBH-saporin: anatomical findings.

The ability to create lesions of discrete neuronal populations is an important strategy for clarifying the function of these populations. The power of this approach is critically dependent upon the selectivity of the experimental lesioning technique. Anti-neuronal immunotoxins offer an efficient way to produce highly specific neural lesions. Two previous immunotoxins have been shown to be effective in both the CNS and PNS. They are OX7-saporin, which is targeted at Thy1, and 192-saporin, which is targeted at the low affinity neurotrophin receptor, p75NTR. In the present study, we sought to determine if an immunotoxin targeted at the neurotransmitter synthesizing enzyme, dopamine beta-hydroxylase (DBH), could selectively destroy central noradrenergic neurons after intraventricular administration. This immunotoxin, which consists of a monoclonal antibody to DBH coupled by a disulfide bond to saporin (a ribosome inactivating protein), has been shown to be selectively toxic to peripheral noradrenergic sympathetic neurons in rats after systemic injection. In the present study, immunohistochemical and Cresyl violet staining showed that the noradrenergic neurons of the locus coeruleus are destroyed bilaterally after intraventricular (i.c.v.) injection of 5, 10, and 20 micrograms of anti-DBH-saporin (alpha-DBH-sap) into rats. Complete bilateral lesioning of the A5 and A7 cell groups occurred at the two higher doses. Lesions of the A1/C1 and A2/C2/C3 cell groups were incomplete at all three doses. Dopaminergic neurons of the substantia nigra and ventral tegmental area and serotonergic neurons of the raphé, all monoaminergic neurons that do not express DBH, survived all alpha-DBH-sap doses. The cholinergic neurons of the basal forebrain, which are selectively killed by i.c.v. injection of 192-saporin, and cerebellar Purkinje cells which are killed by OX7-saporin, were not killed by alpha-DBH-sap. These results show that alpha-DBH-sap efficiently and selectively destroys CNS noradrenergic neurons after i.c.v. injection. The preferential destruction of locus coeruleus, A5, and A7 over A1/C1 and A2/C2/C3 may be due to more efficient access of the immunotoxin to these neurons and their terminals after i.c.v. injection.

Adrenergic Fibers↗