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Biomedical subjects

N Jordan

Publications and source records attributed to N Jordan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes.

BACKGROUND: Regulation of the inflammatory response within the human lung is essential to prevent this important part of the normal host defence response becoming a pathological process. Tumour necrosis factor alpha (TNF-alpha) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis in many organ systems including the lung. Interleukin 10 (IL-10) has been proposed as having an inhibitory effect on the production of several inflammatory cytokines including TNF-alpha. METHODS: The effect of IL-10 administration on TNF-alpha production was explored in human alveolar macrophages and peripheral blood monocytes from matched individuals. The effects of IL-10 on TNF-alpha protein production were determined by sandwich enzyme linked immunosorbant assay (ELISA), whereas the TNF-alpha mRNA response was established by Northeren blotting using a TNF-alpha specific oligonucleotide probe. The protein synthesis inhibitors actinomycin D and cyclohexamide were utilised to monitor IL-10 effects on mRNA degradation and de novo protein synthesis, respectively. RESULTS: The lipopolysaccharide-mediated TNF-alpha production in alveolar macrophages was reduced from 3.508 (0.629) to 2.035 (0.385) ng/ml by 100 U/ml IL-10. Lipopolysaccharide-induced TNF-alpha production in peripheral blood monocytes was reduced from 2.035 (0.284) to 0.698 (0.167) ng/ml. TNF-alpha gene expression was also inhibited in both alveolar macrophages and peripheral blood monocytes; lipopolysaccharide-induced TNF-alpha mRNA was reduced by 47.8 (15.2)% and 83.1 (4.2)%, respectively, by IL-10. The IL-10 mediated suppression of TNF-alpha mRNA was unaffected by addition of cyclohexamide, suggesting that de novo protein synthesis was not required for TNF-alpha inhibition. mRNA stability experiments indicated no acceleration in lipopolysaccharide-induced TNF-alpha mRNA degradation in response to IL-10. CONCLUSIONS: These findings suggest that IL-10 is a potent inhibitor of TNF-alpha expression and release from alveolar macrophages and peripheral blood monocytes, and thus it may have an important role in the cytokine network of the pulmonary immune response.

Adult↗
PubMed1994

Slowed central processing in simple and go/no-go reaction time tasks in Parkinson's disease.

Studies of cognition and motor control have independently suggested that patients with Parkinson's disease show deficits in both attentional control and the preprogramming of movement. However, few studies have examined directly the involvement of cognitive processes in the origin of their slowed response. We examined the performance of 100 Parkinson's disease patients on simple reaction time (SRT) and a series of go/no-go cross-modality choice reaction time (CRT) tasks, in which motor response was constant; correct positive responses required attention to a progressively increasing number of dimensions of visual and auditory stimuli. The results showed that Parkinson's disease patients became increasingly impaired in response speed as choice complexity increased. Slowed response speed in Parkinson's disease involved two factors: (i) a 'perceptuomotor' factor which was constant across conditions and independent of choice complexity. Depression affected this factor selectively and independently of confounding associations with impoverished motor control; (ii) a 'cognitive-analytical' factor, which played an increasingly important role as complexity of choice increased. The characteristics of the relationship between response latency and cognitive complexity indicate that the deficit was due to a constant proportional slowing in cognitive speed across all SRT and CRT conditions. A cognitive deficit affecting the monitoring of stimulus-response compatibility may contribute to delayed response in Parkinson's disease. This cognitive-analytical deficit is present in early, untreated cases and, in contrast to perceptuomotor processes, is weakly related to depression.

Aged↗
PubMed1994

Long-term prognosis of transient lone bilateral blindness in adolescents and young adults.

We describe a group of 14 patients aged 8-38 years at presentation who had one or more sudden transient attacks of bilateral blindness. Eight patients described bilateral blindness as their only symptom whereas six others experienced some mild associated symptoms. Visual loss always developed within seconds and attacks were often precipitated by exercise, stress, or postural change. Of 13 patients available for review, none suffered a major vascular event during a mean follow up of 10 years. When adolescents and young adults present with transient bilateral blindness, investigations are unlikely to reveal a cause and the long-term prognosis appears benign.

Adolescent↗
PubMed1994

The role of the striatum in motor learning: dissociations between isometric motor control processes in Parkinson's disease.

Studies of Parkinson's disease (PD) have been used to support the hypothesis that the striatum serves procedural learning but interpretation of the results is confounded by extra-striate pathology and coincidental non-procedural cognitive deficits. The motor deficit of PD involves particularly internally cued movement, without visual feedback, because of disruption to frontostriatal circuits. Thus, we used a non-visual isometric task as a sensitive measure of motor learning in early non-demented patients with PD and examined the effects of dopamine replacement. The PD group showed disproportionate under-shooting of the target but normal motor learning. Learning correlated with some cognitive measures but not clinical motor disability or depression. Treatment had no effect on performance, despite clinical improvement. The results indicate dissociations between motor control processes resulting from striatal pathology. Putaminal circuits are involved in force generation and prediction but not critically in motor learning.

Basal Ganglia↗
PubMed1992

Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients.

The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.

Adult↗
PubMed1992

A component analysis of the generation and release of isometric force in Parkinson's disease.

Paradigms of isometric force control allow study of the generation and release of movement in the absence of complications due to disordered visuomotor coordination. The onset and release of isometric force in Parkinson's disease (PD) was studied, using computerised determinants of latency of response and rate of force generation and release. Components of isometric force control were related to measures of cognitive, affective and clinical motor disability. The effects of treatment were determined by longitudinal study of de novo patients. Patients with PD showed impairment in latency and rate of force change for movement release as well as onset. Rate of force change correlated with depression, clinical motor disability and memory quotient but latency showed no correlation with any of these measures. Treatment improved rate of force release, in concert with clinical motor disability, but not latency. These results suggest dissociations between latency and rate of force change that may be linked to different neurochemical deficits. Further, they demonstrate akinetic deficits in force release that argue against the "neural energy hypothesis" of akinesia.

Bromocriptine↗
PubMed1992

Cognitive components of reaction time in Parkinson's disease.

Studies of reaction time in Parkinson's disease (PD) have suggested a selective deficit in simple reaction time (SRT), compared with choice reaction time (CRT). This finding has been interpreted as a deficit in motor preprogramming but could involve other factors, such as attentional focussing and stimulus predictability. Moreover, not all studies show the same selective deficit, possibly because of differences in patient selection and treatment effects. The neurochemical basis of RT deficits in PD remains unclear. Accordingly, the contribution of cognitive factors to impaired RT was assessed in a large group of PD patients, including early untreated cases, and performance was examined in relation to clinical variables and the effect of treatment in longitudinal study. Motor output was constant in both SRT and CRT tasks. In the SRT task, all stimuli required a response; in the CRT task, subjects were required to respond to only one of the two possible stimuli. Attentional focussing on SRT was examined by variation of the interval between cue and stimulus; effects of stimulus uncertainty were evaluated from a comparison of SRT and CRT; temporal predictability of the stimulus was examined from a comparison of conditions in which the interval between warning signal and imperative stimulus was constant or variable. The PD patients showed similar deficits in SRT and CRT, but normal effects of cue-stimulus interval and temporal predictability. Reaction time correlated with measures of global cognitive capacity and frontal-lobe function, as well as motor disability. Treatment had no effect on SRT or CRT, despite clinical benefit. These findings indicate that RT deficits in PD are not due to impaired attentional focussing or stimulus predictability but are compatible with a deficit in higher-order processes concerned with the orientation of both cognitive and motor responses to a stimulus. These processes are not substantially dopamine-dependent but may be served by non-dopaminergic neurotransmission.

Antiparkinson Agents↗
PubMed1991

Normal release from proactive interference in untreated patients with Parkinson's disease.

The relationship of release from proactive interference (PI) to set-shifting, explicit free recall and language remains controversial. We tested 56 patients with Parkinson's disease (PD) who had never received medication and 37 matched normal control subjects on a test of PI release based on semantic category. The PD group showed normal PI release but impaired word recall. PI release was independent of impaired Wisconsin card-sorting test performance, language production, explicit memory, overall cognitive status and severity of depression. The results indicate dissociation between ability to benefit from semantic stimulus properties and processes of explicit memory, set-shifting and expressive language.

Attention↗
PubMed1991

Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability.

Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.

Adult↗
PubMed1990

Abnormalities of central motor conduction in Parkinson's disease.

The new technique of magnetic stimulation was used to measure amplitude of the motor evoked potential (MEP) recorded from abductor digiti minimi whilst stimulating at the head, and motor conduction time (MCT) between head and neck. Bilateral studies were made in 12 normal subjects and 56 patients with Parkinson's disease. The amplitudes of the MEPs were significantly larger (P less than 0.05) in the patients (mean 1.6 mV, SD 1.4) compared with the normal subjects (mean 0.9 mV, SE 0.6). MCTs were significantly shorter (P less than 0.001) in patients (mean 8.1 ms, SD 1.3) compared with the normal subjects (mean 9.4 ms, SD 1.2). Although the pathophysiological basis of these changes has not been determined, they provide objective measurements which may be clinically valuable in monitoring therapy.

Central Nervous System↗
PubMed1988

Application of HPLC with a metal-free column to the analysis of cyclosporin in whole blood samples from cardiac transplant patients.

A simplified, reverse-phase HPLC method utilizing a metal-free column was developed for the analysis of cyclosporin (CYA) in whole blood in humans. The average intra and inter assay variation at the low end of the therapeutic range are less than or equal to 4.5 and 8.8% respectively. The procedure was successfully applied to the measuring of CYA in whole blood collected from cardiac transplant patients over a one year period.

Chromatography, High Pressure Liquid↗
PubMed1987

Characterization of digoxin and related cardiac glycosides by fast atom bombardment mass spectrometry.

The potential of using fast atom bombardment mass spectrometry for the detection and the characterization of digoxin and a series of related cardenolide analogues was investigated. The spectra were dependent upon the type of support-matrix in which they were recorded; thioglycerol proved to be satisfactory for the characterization of digoxin and allowed for its detection in human urine extract spiked with ca 11 ng ml(-1).

Journal Article↗