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Biomedical subjects

N J Scolding

Publications and source records attributed to N J Scolding.

At least 37 records · Page 2Linked to original sources
PubMed1999

Microangiopathy of the brain and retina with hearing loss in a 50 year old woman: extending the spectrum of Susac's syndrome.

A 50 year old woman presented with a subacute onset of vertigo and diplopia followed by an encephalopathy with confusion, spasticity, ataxia, myoclonus, and multiple branch retinal arteriolar occlusions and unilateral sensorineural deafness. Brain biopsy confirmed multiple microinfarcts with no vasculitis. After the procedure she had a right iliofemoral deep vein thrombosis and was found to be heterozygous for the factor V Leiden mutation. She was treated with anticoagulants and made a marked recovery with no relapses 6 months after presentation. This case extends the age range at which Susac's syndrome can present, and raises the possibility that the condition may be associated with abnormalities of coagulation.

Brain↗
PubMed1998

Interferon-beta inhibits mitogen induced astrocyte proliferation in vitro.

The central nervous system response to injury and inflammation commonly includes astrocytosis. This process, which is manifest by astrocyte hypertrophy and proliferation, is particularly prominent in multiple sclerosis (MS), where in chronic lesions it may contribute to the lack of repair by restricting the migration of remyelinating cells. Interferon-beta (IFN-beta) modestly reduces the frequency of relapses in MS and may have a small effect on the accumulation of permanent disability. Here, we show that IFN-beta inhibits the in vitro proliferative response of rodent astrocytes to a wide variety of growth factors and cytokines. Although important species differences exist in these glial responses this previously unrecognised property of IFN-beta may have implications for reducing astrocytosis and thereby promoting endogenous repair.

Animals↗
PubMed1998

The expression of complement regulatory proteins by adult human oligodendrocytes.

In multiple sclerosis, infiltrating T lymphocytes and perivascular microglia may initiate demyelinating lesions, but a role for antibody and complement in the ensuing inflammatory damage to myelin and oligodendrocytes is likely. In most tissues, ubiquitously expressed complement regulatory proteins prevent autologous destruction, protecting host cells from the powerful cytolytic activity of activated complement. We have studied the surface expression of a comprehensive range of complement regulatory proteins by live adult human oligodendrocytes in vitro. Only DAF of the activation pathway regulators was expressed, not CR1 or MCP. Of the membrane attack pathway regulatory proteins, HRF was not expressed, while substantial heterogeneity of CD59 expression by oligodendrocytes was found. Clusterin expression was not found. A relative deficiency of protective complement regulatory proteins on human oligodendrocytes may contribute to their selective damage in multiple sclerosis.

CD59 Antigens↗
PubMed1998

Adult polyglucosan body disease associated with an extrapyramidal syndrome.

A 50 year old patient is described who presented with parkinsonism, frontal dementia, peripheral neuropathy, neurogenic bladder, and upper motor neuron signs. No improvement in objective measurements of extrapyramidal dysfunction were seen with an incremental apomorphine test or more prolonged oral dopamine challenge. Neurophysiology disclosed changes compatible with a diffuse axonal neuropathy and pathological examination of a length of sural nerve taken at biopsy showed multiple polyglucosan bodies characteristic of adult polyglucosan body disease (APGBD). This case underlines the diverse clinical presentation of this rare neurological disease and the importance of recognising the unusual association of clinical features in making the diagnosis. APGBD should be included in the differential diagnosis of parkinsonism unresponsive to dopaminergic therapy.

Adult↗
PubMed1997

beta-Interferon regulates the immunomodulatory activity of neonatal rodent microglia.

beta-interferon (beta-IFN) has both pro and anti-inflammatory properties, the balance of which leads to some suppression of disease activity in multiple sclerosis patients. Here, we examine the immunomodulation of neonatal rodent microglia, the principal CNS accessory cell, by beta-IFN and consider the interaction of beta-IFN and gamma-interferon (gamma-IFN). beta-IFN and gamma-IFN inhibit microglial proliferation. beta-IFN antagonises both gamma-IFN-induced upregulation of class II expression and the ability of gamma-IFN primed cells to mount a respiratory burst. In contrast, beta-IFN upregulates microglial Fc receptor expression and augments tumour necrosis factor alpha secretion from suboptimally stimulated microglia.

Adjuvants, Immunologic↗
PubMed1997

Beta-interferon and multiple sclerosis.

Interferon-beta (IFN-beta) is the first therapeutic intervention shown to alter the natural history of multiple sclerosis (MS), a relapsing then progressive inflammatory degenerative disease of the CNS. Since publication of the first randomized placebo-controlled trial of IFN-beta, and subsequent acquisition of US and European product licences for use in relapsing-remitting MS, the hopes and expectations of patients have been elevated greatly only to be dampened as more critical analysis of the trial results, in conjunction with the cost of treatment, led to marked limitations on prescription in several countries. IFN-beta is not a cure. Here we review what is known about the mechanisms of action of IFN-beta in demyelinating disease, and propose a possible model of action of IFN-beta in the treatment of MS.

Humans↗
PubMed1997

Cerebral vasculitis--recognition, diagnosis and management.

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.

Adult↗
PubMed1997

Remyelination in demyelinating disease.

In multiple sclerosis, partial remyelination is conspicuous in many lesions, and is thought to contribute significantly to lasting recovery from acute relapse. However, myelin repair ultimately fails during progression of the disease, as disability and handicap accumulate. In this chapter we explore the biological background to myelin repair in CNS demyelinating disease, and the reasons underlying the failure of more widespread and lasting remyelination in multiple sclerosis. Experimental studies provide clear evidence that therapies promoting myelin repair can be highly successful in the CNS, and we discuss the clinical approaches which might allow the translation of these laboratory studies to neurological practice, together with some of the potential hazards and pitfalls likely to arise.

Animals↗
PubMed1996

Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy.

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.

Adolescent↗
PubMed1995

A proliferative adult human oligodendrocyte progenitor.

The failure of oligodendrocytes to sustain repair of demyelinated axons contributes to the cumulative neurological disability which characterizes multiple sclerosis. In the rodent, transplanted neonatal glial progenitors efficiently remyelinate gliotoxic lesions. Proliferative bipotential progenitors are also present in the adult rat, but have not hitherto been identified in adult human tissue. Here we demonstrate cells in cultures of adult human temporal lobe which are morphologically and immunocytochemically identical to rate progenitors, are bipotential, and exhibit an astrocyte-driven proliferative response. The identification of an adult human oligodendrocyte progenitor is the first step towards developing interventional strategies for promoting repair of demyelinated lesions in patients with multiple sclerosis.

Astrocytes↗
PubMed1995

Growth factors fail to protect rat oligodendrocytes against humoral injury in vitro.

CNS growth factors protect neurons and glia against a wide variety of insults in vitro and in vivo by mechanisms which include buffering toxic rises in intracellular calcium. Cytosolic calcium elevation also plays a key role in complement injury, but the possibility that growth factors protect against antibody-mediated complement attack has not hitherto been addressed. In multiple sclerosis, antibodies and complement appear to contribute to the selective targeting and damage of oligodendrocytes and myelin. Here we have investigated the possibility that growth factors active in oligodendrocyte development and differentiation might protect these cells against injury mediated by antibody and complement in vitro. None was found to be protective.

Animals↗
PubMed1995

Auctioneer's jaw: a case of occupational oromandibular hemidystonia.

An auctioneer is described in whom focal dystonia of the jaw developed as an occupational symptom, occurring solely and predictably when he commenced his selling "patter" and resolving quickly on stopping. He responded well to treatment with intramuscular botulinus toxin.

Adult↗
PubMed1994

Cerebrospinal fluid concentrations of the complement MAC inhibitor CD59 in multiple sclerosis and patients with other neurological disorders.

Rodent oligodendrocytes have a unique susceptibility among glia to the lytic effects of complement, due in part to a deficiency in CD59 (protectin), a key surface inhibitor of the complement membrane attack complex (MAC). The possibility that shedding of CD59 by human oligodendrocytes contributes to complement-mediated oligodendrocyte injury in inflammatory demyelinating disease has been investigated by estimating levels of CD59 in cerebrospinal fluid samples from 12 patients with demyelinating disease of the central nervous system and 13 with other neurological diseases. No significant differences were found between patients and controls, or between patients with active and those with clinically inactive demyelinating disease, providing no direct support for oligodendrocyte shedding of CD59 in multiple sclerosis.

Antigens, CD↗
PubMed1994

Micrographia associated with a parietal lobe lesion in multiple sclerosis.

The occurrence of micrographia in a 52 year old women two years after an isolated episode of painful sensory disturbance led to the diagnosis of multiple sclerosis. Her handwriting returned to normal after a course of intravenous methylprednisolone. Previous reports of movement disorders occurring in the context of multiple sclerosis are briefly reviewed. The finding on MRI studies of an enhancing lesion in the dominant parietal white matter supports Kinnier Wilson's suggestion that the anatomical origin of micrographia lies in the cerebral hemisphere rather than the corpus striatum.

Brain Diseases↗
PubMed1992

The role of calcium in rat oligodendrocyte injury and repair.

The role of intracellular calcium in oligodendrocyte injury is investigated using cultured rat oligodendrocytes. Calcium ionophores A23187 and ionomycin mimic both complement and perforin attack, causing oligodendrocyte lysis at concentrations which do not lyse other glia. Membrane vesiculation, the mechanism by which oligodendrocytes resist and recover from complement and perforin attack, is also induced by A23187. Oligodendrocytes are more susceptible to complement attack in the presence of a calmodulin inhibitor (W7), which also inhibits vesiculation. These results imply that calmodulin is involved in membrane repair from complement attack, and indicate that changes in intracellular calcium play an important yet paradoxical role in the oligodendrocyte response to injury, dictating both susceptibility and cellular recovery.

Animals↗
PubMed1992

Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing.

Interactions between rat microglia and oligodendrocytes were examined in vitro in order to characterize the stages of adherence, phagocytosis and cytotoxicity against oligodendrocytes by microglia. Under resting conditions, microglia showed minimal contact with oligodendrocytes and exhibited surface staining of myelin basic protein and myelin debris only; they were not cytotoxic for oligodendrocytes and did not produce tumour necrosis factor (TNF). On activation with either gamma-interferon or lipopolysaccharide and interferon, these cells increased surface binding for myelin basic protein, showed greater contact with living oligodendrocytes and produced TNF in both secreted and cell surface bound forms. Secreted TNF was capable of killing oligodendrocytes but the cell surface bound form did this more efficiently. In the presence of complement, activated microglia showed significant phagocytosis of myelin basic protein which was not obvious in the unactivated cells. These results suggest that activated microglia in the presence of complement are sufficient to kill and phagocytose the oligodendrocyte-myelin complex in vitro.

Animals↗