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Biomedical subjects

D Kidd

Publications and source records attributed to D Kidd.

At least 19 recordsLinked to original sources
PubMed2001

Protein kinase C activation by 12-0-tetradecanoylphorbol 13-acetate in CG-4 line oligodendrocytes stimulates turnover of choline and ethanolamine phospholipids by phospholipase D and induces rapid process contraction.

Treatment of [3H]-choline- or [14C]-ethanolamine-labelled undifferentiated bipolar and differentiated multipolar CG-4 line oligodendrocytes with 12-0-tetradecanoylphorbol 13-acetate (TPA) to activate protein kinase C stimulated the release of choline or ethanolamine metabolites to the medium over controls. Ro31-8220, a PKC inhibitor, reduced TPA-stimulated release of choline- and ethanolamine-metabolites to basal levels. TPA treatment of both bipolar and multipolar cells caused rapid contraction of processes leaving rounded up cells: this effect was blocked by Ro31-8220. After 12-15 h exposure to TPA, bipolar undifferentiated CG-4 line cells extended short processes again and the cells became multipolar. Nocodozole, an agent which disrupts microtubules and caused CG-4 line cells to round up, caused increased choline or ethanolamine-metabolite release to the medium over basal levels suggesting that some release during TPA-treatment might occur due to process fragmentation. However, the transphosphatidylation reaction confirmed that phospholipase D was active in these cells. Exposure of bipolar undifferentiated CG-4 line cells to TPA resulted in down-regulatation of PKC-alpha and PKC-beta which could not be detected by Western blotting after a few hours; PKC-epsilon was down-regulated much more slowly but PKCs delta, zeta and iota were not influenced by 48 h exposure of cells to TPA. Formation of phosphatidylethanol in the transphosphatidylation reaction was markedly reduced in TPA down-regulated cells indicating a role for PKCs alpha and beta in phospholipase D activation in CG-4 line oligodendrocytes.

Animals↗
PubMed2000

D-TACC: a novel centrosomal protein required for normal spindle function in the early Drosophila embryo.

We identify Drosophila TACC (D-TACC) as a novel protein that is concentrated at centrosomes and interacts with microtubules. We show that D-TACC is essential for normal spindle function in the early embryo; if D-TACC function is perturbed by mutation or antibody injection, the microtubules emanating from centrosomes in embryos are short and chromosomes often fail to segregate properly. The C-terminal region of D-TACC interacts, possibly indirectly, with microtubules, and can target a heterologous fusion protein to centrosomes and microtubules in embryos. This C-terminal region is related to the mammalian transforming, acidic, coiled-coil-containing (TACC) family of proteins. The function of the TACC proteins is unknown, but the genes encoding the known TACC proteins are all associated with genomic regions that are rearranged in certain cancers. We show that at least one of the mammalian TACC proteins appears to be associated with centrosomes and microtubules in human cells. We propose that this conserved C-terminal 'TACC domain' defines a new family of microtubule-interacting proteins.

Amino Acid Sequence↗
PubMed2000

Late onset heterozygous ornithine transcarbamylase deficiency mimicking complex partial status epilepticus.

A 57 year old woman with post-traumatic complex partial seizures was admitted because of recurrent episodes of altered mental state over the preceding 4 years, each lasting up to 5 days. There was a history of dietary protein intolerance since childhood and two of her daughters had died in the neonatal period from unexplained encephalopathies. In hospital she developed fluctuating confusion, amnesia, and sudden episodes of unresponsiveness. An EEG was consistent with complex partial status epilepticus but there was no response to benzodiazepines. Nasogastric feeding and sodium valproate were given and shortly afterwards she lapsed into a deep coma. Blood ammonia and urinary orotate were raised, and genetic testing confirmed that she was a carrier of a mutation in exon 3 of the ornithine transcarbamylase gene (C to T at position 92). Treatment with protein restriction, carnitine, and sodium phenylbutyrate led to a full recovery over a period of 3 months. To our knowledge this is the oldest age of onset yet described in a manifesting carrier. She is the fifth patient with heterozygous ornithine transcarbamylase deficiency reported to have had a severe reaction to sodium valproate. Hyperammonaemic encephalopathy should be considered in patients of any age who experience fluctuating confusion.

Diagnosis, Differential↗
PubMed1999

Substratum of pleiotrophin (HB-GAM) stimulates rat CG-4 line oligodendrocytes to adopt a bipolar morphology and disperse: primary O-2A progenitor glial cells disperse similarly on pleiotrophin.

Pleiotrophin (HB-GAM), an extracellular matrix-associated protein with a high content of basic amino acid residues, is expressed in the central nervous system during late pre- and early post-natal development and promotes neurite outgrowth in vitro. Here, we show that, on a substratum of pleiotrophin formed from a 5 or 10 microg/ml solution, undifferentiated rat CG-4 line oligodendrocytes adopt a bipolar morphology and disperse over the substratum, as we have previously shown with poly-L-lysine (Rumsby et al. Neurosci. Res. Commun. 23:101-109, 1998). On pleiotrophin substrata formed from coating solutions of 1 microg/ml and below, CG-4 line cells form aggregates and do not disperse, as is also the case with poly-L-lysine. The same dispersing effect is observed with rat primary 0-2A progenitor glial cells on pleiotrophin substrata from solutions of 5 and 10 microg/ml: 0-2A cells aggregate together on pleiotrophin substrata formed from lower concentrations and do not disperse. A pleiotrophin substratum enhances proliferation of CG-4 line oligodendrocytes and primary 0-2A progenitor glial cells. The results show that pleiotrophin provides a substratum that can influence progenitor oligodendrocyte morphology, aid cell dispersion, and perhaps also enhance progenitor oligodendrocyte cell growth.

Animals↗
PubMed1999

Cortical lesions in multiple sclerosis.

Although previous studies have shown that the lesions of multiple sclerosis may involve the cerebral cortex, there is little published research on the prevalence and distribution of such lesions. Using neuropathological techniques and MRI, a series of studies has been undertaken in order to assess this, in particular to identify their relationship to cortical veins. A serial MRI study showed that the use of gadolinium proffered an increase in cortical lesion detection of 140% and showed that 26% of active lesions arose within or adjacent to the cortex. In a post-mortem study, MRI under-reported lesions subsequently analysed neuropathologically, particularly those arising within the cortex. In a further 12 cases examined, 478 cortical lesions were identified, of which 372 also involved the subcortical white matter. Seven different lesion types were identified; the majority arose within the territory of the principal cortical veins, whilst the remaining quarter arose within the territory of the small branch or superficial veins. Small cortical lesions are common in multiple sclerosis and are under-reported by MRI. Investigation of the cortical venous supply shows how such lesions may arise, and why the majority also involve the underlying white matter.

Adult↗
PubMed1999

Neurological complications in Behçet's syndrome.

The neurological complications of Behçet's syndrome have not been characterized with clarity. We present the clinical features, imaging characteristics and CSF findings of a series of 50 patients seen at the National Hospital for Neurology and Neurosurgery over the past 10 years. In this series, vascular complications had a low prevalence, whereas involvement of the brainstem was common; spinal cord lesions, hemisphere lesions and meningoencephalitis also occurred. Optic neuropathy, vestibulocochlear and peripheral nerve involvement occurred, but were rare. The prognosis for recovery was in general good, and the majority of those followed-up over a median of 3 years (range 1-19 years) had only single attacks. One-third of patients underwent further attacks, and four underwent progressive deterioration leading to disability. Factors suggesting a poor prognosis are repeated attacks, incomplete recovery, progressive disease course and a high level of CSF leucocytosis during acute attack. These data should be of help in the further definition of the clinical characteristics of this rare neurological disorder and in the planning of treatment trials.

Adult↗
PubMed1999

Spatz-Lindenberg disease: a rare cause of vascular dementia.

BACKGROUND: Isolated cerebral thromboangiitis obliterans (Spatz-Lindenberg disease) is not well recognized as a cause of vascular dementia. CASE DESCRIPTION: A 58-year-old woman presented with dementia and pyramidal signs. Neuroimaging showed multiple areas of white matter change. Brain biopsy showed intimal thickening of the walls of leptomeningeal and intraparenchymal arteries, almost to complete occlusion, with an intact internal elastic lamina and media and without inflammation or infiltration. The cortex showed only moderate gliosis. CONCLUSIONS: Spatz-Lindenberg disease should be considered in the differential diagnosis of vascular dementia. Additional studies of its pathogenesis are required to determine appropriate treatment.

Cerebrovascular Disorders↗
PubMed1998

Central motor conduction time in progressive multiple sclerosis. Correlations with MRI and disease activity.

The purpose of this study was to relate abnormalities of motor conduction time to the presence of spinal cord MRI lesions in progressive multiple sclerosis and to investigate the relationship between changes in motor conduction over time and clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the brain and spinal cord, and clinical evaluations were carried out in 20 patients with primary and secondary progressive multiple sclerosis. CMCT was carried out at the beginning and end of the study whilst the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior correlated with disability measured on the Expanded Disability Status Scale. Latencies to upper limb muscles correlated with cervical MRI lesion load and the presence of atrophy of the cervical cord. Over the 12-month study period, 15 of 19 patients deteriorated clinically. However, an increase in motor response latencies occurred only in the four patients who had developed new cord lesions. The results suggest that prolonged CMCT is related to spinal cord lesion load and that, over time, changes in the CMCT occur only when spinal cord lesion load increases. Clinical change in progressive multiple sclerosis may therefore occur without either the development of new lesions on MRI scans or an increase in motor conduction time. This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing demyelination. This may be progressive axonal degeneration.

Adult↗
PubMed1997

The transverse magnetisation decay characteristics of longstanding lesions and normal-appearing white matter in multiple sclerosis.

The characteristics of transverse magnetisation decay of 120 longstanding lesions and 40 regions of normal-appearing white matter have been analysed in 40 patients with multiple sclerosis (MS) and 10 normal controls. Fifty lesions showed a biexponential decay in which two water compartments-one probably intracellular, the other extracellular-could be defined. There was a higher frequency of biexponential lesions in patients with a primary progressive course but no significant difference between benign and secondary progressive groups. Seventy lesions showed a monoexponential decay, of which 31 showed a T2 of greater than 200 ms, implying that these lesions were predominantly composed of extracellular rather than intracellular water. The results imply that an expanded extracellular space within chronic MS brain lesions is a common finding at all levels of disability and disease course. In so far as an expanded extracellular space implies axonal loss, the results suggest that the latter occurs commonly in longstanding MS lesions. The lack of correlation with disability suggests a limited role for the technique in therapeutic monitoring.

Adult↗
PubMed1997

Cost-effectiveness analysis of spinal cord stimulation in treatment of failed back surgery syndrome.

This article presents an analysis of the medical costs of spinal cord stimulation (SCS) therapy in the treatment of patients with failed back surgery syndrome (FBSS). We compared the medical costs of SCS therapy with an alternative regimen of surgeries and other interventions. Externally powered (external) and fully internalized (internal) SCS systems were considered separately. Clinical management models of each of the therapy alternatives were derived from the clinical literature, retrospective data sets, expert opinion, and published diagnostic and therapy protocols. No value was placed on pain relief or improvements in the quality of life that successful SCS therapy can generate. We found that by reducing the demand for medical care by FBSS patients, SCS therapy can lower medical costs. On average, given current screening and efficacy rates, SCS therapy pays for itself within 5.5 years. For those patients for whom SCS therapy is clinically efficacious, the therapy pays for itself within 2.1 years.

Back Pain↗
PubMed1997

Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis.

The aim of this study was to assess neopterin, a marker of interferon gamma (IFN-gamma) induced macrophage activity, as a possible surrogate marker of inflammation in patients with multiple sclerosis. Urinary neopterin to creatinine ratios (UNCRs) were measured daily in 10 primary progressive (PP). 10 relapsing remitting (RR) and 11 secondary progressive (SP) patients with multiple sclerosis, and 14 normal control (NC) subjects, for periods of up to 12 weeks. After excluding measurements related to infection, the median of the individuals' average UNCRs was significantly higher in patients than in controls (P < 0.001 for all patients and P < 0.01 for each of the three groups of patients); the median UNCRs (and interquartile ranges) were 187 (135-231), 187 (165-277), 218 (164-517) and 134 (97-152) mumol/mol for PP, RR, SP patients and controls, respectively. Similarly, patients had a greater median proportion of days with a UNCR above normal (P < 0.001 for all patients and P < 0.01 for each group); the median percentage (and interquartile ranges) were 16 (6-62), 28 (21-36), 49 (14-86) and 0 (0-6)% for PP, RR, SP patients and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls (P < 0.001 for all patients and P < 0.01 for each group); the means +/- SD peaks/subject/month were: 2.1 +/- 1.8; 3.0 +/- 1.7; 3.3 +/- 2.3 and 0.2 +/- 0.6 for PP, RR, SP patients and controls, respectively. Nine relapses occurred in nine patients during the study, and all were associated with increased neopterin excretion, which tended to be greater than that on days not associated with a relapse. Three of the nine relapses were preceded by an upper respiratory tract infection. In eight out of 13 patients who had infections during the study, increased neopterin excretion was noted for periods of up to 6 weeks post-infection, significantly longer than that which occurred after infections in controls. This confirms infection as a potent inducer of symptomatic and asymptomatic disease activity in mutiple sclerosis, and provides further support of a pivotal role for IFN-gamma in te pathogenesis of mutiple sclerosis. Urinary neopterin excretion is increased in patients with both progressive and relapsing mutiple sclerosis, and therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis disease activity.

Adult↗