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Biomedical subjects

A J Thompson

Publications and source records attributed to A J Thompson.

At least 19 recordsLinked to original sources
PubMed1992

Cleavage and recognition pattern of a double-strand-specific endonuclease (I-creI) encoded by the chloroplast 23S rRNA intron of Chlamydomonas reinhardtii.

Several group-I introns have been shown to specifically invade intron-minus alleles of the genes that contain them. This type of intron mobility is referred to as 'intron homing', and depends on restriction endonucleases (ENases) encoded by the mobile introns. The ENase cleaves the intron-minus allele near the site of intron insertion, thereby initiating gene conversion. The 23S (LSU) rRNA-encoding gene (LSU) of the chloroplast genome of Chlamydomonas reinhardtii contains a self-splicing group-I intron (CrLSU) that has a free-standing open reading frame (ORF) of 163 codons. Translation of CrLSU intron RNA in cell-free systems produces a polypeptide of approx. 18 kDa, the size expected for correct translation of the ORF. The in vitro-synthesized 18-kDa protein cleaves plasmid DNA that contains a portion of LSU where the intron normally resides, but lacking the intron itself. Cleavage by the intron-encoded enzyme (I-CreI) occurs 5 bp and 1 bp 3' to the intron insertion site (in the 3'-exon) in the top (/) and bottom (,) strands, respectively, resulting in 4-nt single-stranded overhangs with 3'-OH termini. We also show that the recognition sequence of I-CreI spans the cleavage site and is 24 bp in length (5'-CAAAACGTC,GTGA/GACAGTTTGGT).

Animals↗
PubMed1992

beta-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: a regulatory role for cortisol and interleukin-1.

An increased density of beta-adrenergic receptors was demonstrated on peripheral blood mononuclear cells (PBMCs) from patients with progressive or relapsing-remitting multiple sclerosis (MS). The same observation was made in patients with chronic active rheumatoid arthritis, but not in those with myasthenia gravis. The affinity of the receptors was within the normal range in all tested groups of patients and there was a positive correlation between density and function as determined by intracellular cyclic AMP production after stimulation with isoproterenol. A putative link between inflammatory process and the functional upregulation of beta-adrenergic receptors on PBMCs was tested by in vitro studies with the soluble mediators interleukin-1 and hydrocortisone. A functional upregulation of beta-adrenergic receptors was observed when PBMCs from normal control subjects were cultured in the presence of either mediator, whereas the already upregulated receptor density on PBMCs from patients with MS remained unchanged. Whether this represents a recovery mechanism to inflammation in MS or a blunting of homeostatic immunoregulatory mechanisms requires further investigation.

Adult↗
PubMed1992

Effects of fine needle aspiration on subsequent mammograms.

The effects of fine needle aspiration on subsequent mammography were studied in a group of women who were referred with palpable breast lumps. Fifty-two women aged between 36 and 73 (median 53) years underwent mammography before and within 5 days of needle aspiration. Preaspiration and postaspiration mammograms were examined 'blind' by one radiologist. In ten cases, a difference was seen between the preaspiration and postaspiration films. In seven (aged 36-50 years) this was due to aspirated cysts. In three the differences were unexpected and were more significant, although the radiological diagnosis was not altered. If this proportion is extrapolated for a large number of patients then significant numbers of artifacts from fine needle aspiration might be seen on mammograms. It is possible that some might be interpreted falsely as malignant and some small cancers might be obscured. Women accepted mammography more readily before aspiration than after.

Adult↗
PubMed1992

High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect.

The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re-enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment.

Adult↗
PubMed1992

EDMUS, a European database for multiple sclerosis.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

Database Management Systems↗
PubMed1991

In vitro self-splicing reactions of the chloroplast group I intron Cr.LSU from Chlamydomonas reinhardtii and in vivo manipulation via gene-replacement.

The group I intron from the chloroplast rRNA large subunit of Chlamydomonas reinhardtii (Cr.LSU) undergoes autocatalytic splicing in vitro. Cr.LSU displays a range of reactions typical of other group I introns. Under optimal conditions, the 5' cleavage step proceeds rapidly, but the exon-ligation step is relatively slow, and no pH dependent hydrolysis of the 3' splice site occurs. A requirement for high temperature and high [Mg2+] suggests involvement of additional splicing factors in vivo. The positions of three cyclization sites of the free intron have been mapped; two of these sites represent reactions analogous to 5'-splice site cleavage, whereas the third is an example of G-exchange. Cr.LSU contains an open reading frame (ORF) potentially encoding an 163 amino acid polypeptide. ORF function has been investigated by using chloroplast gene replacement via particle bombardment. We have shown that the ORF can be deleted from Cr.LSU without affecting splicing in vivo and it thus does not encode an essential splicing factor.

Adenosine Triphosphate↗
PubMed1991

Major differences in the dynamics of primary and secondary progressive multiple sclerosis.

In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated. In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI over a 6-month period. The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced. Enhancement also occurred within and at the edge of preexisting lesions. In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced. There was no difference in the degree of clinical deterioration between the two groups over the 6-month period. These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.

Adult↗
PubMed1991

Multiple sclerosis and HLA: is the susceptibility gene really HLA-DR or -DQ?

Seventy-one patients with multiple sclerosis (MS) were classified into four subgroups according to the clinical pattern of their disease; their HLA-DR and DQ polymorphisms were defined by serological methods and analysis of Taq1 digestion fragments hybridizing with DRB, DQA, and DQB cDNA probes. The frequencies of the polymorphisms in the patients were compared with those of 100 control subjects. The frequencies of a 3.25-kb fragment from Mspl digests of genomic DNA which hybridized to DQA were also defined in the same groups of patients and control subjects. HLA-DR2 (DRw 15 subtype) and the associated HLA-DQw6 were observed in significant excess in the patients compared with the normal subjects (63% vs. 32% for DRw15; 65% vs. 42% for DQw6). There were no significant differences in the distribution of the DR or DQ alleles between the groups of patients showing different clinical patterns of disease, nor was there an excess in the patients of DQw8 and DQw9 which share hypervariable region sequences of the DQB chain in common with DQw6. The results argue against two recently proposed hypotheses of MS. First, they are not consistent with the proposal that susceptibility to MS is associated with expression of a hypervariable region of DQB shared by DQw6, 8, and 9. Second, they do not support the concept that primarily chronic progressive and relapsing/remitting MS are two immunogenetically distinct disease entities. Our evidence is consistent with the hypothesis that one of the true disease susceptibility genes for MS lies elsewhere within the HLA region and in Northern European populations is found in significant association with DRw15 and DQw6.

Adult↗
PubMed1991

Self-splicing of the Chlamydomonas chloroplast psbA introns.

We used alpha-32P-GTP labeling of total RNA preparations to identify self-splicing group I introns in Chlamydomonas. Several RNAs become labeled with alpha-32P-GTP, a subset of which is not seen with RNA from a mutant that lacks both copies of the psbA gene. Hybridization of the GTP-labeled RNAs to chloroplast DNA indicates that they originate from the psbA and rrn 23S genes, respectively, the only genes known to contain group I introns in this organism. Introns 1, 2, and 3 of psbA (with flanking exon sequences) were subcloned and transcribed in vitro. The synthetic RNAs were found to self-splice; splicing required Mg2+, GTP, and elevated temperature. In addition, the accuracy of self-splicing was confirmed for introns 1 and 2, and intermediates in the splicing reactions were detected. These results, together with our recent data on the 23S intron, indicate that the ability to self-splice is a general feature of Chlamydomonas group I introns. These findings have significant implications for the mechanism of group I intron splicing and evolution in Chlamydomonas and other chloroplast genomes.

Animals↗
PubMed1991

Biochemical changes within a multiple sclerosis plaque in vivo.

Magnetic resonance spectroscopy (MRS) was performed on a superficial part of the brain containing a large multiple sclerosis (MS) lesion. Reduced levels of phosphocreatine (PCr) relative to adenosine triphosphate (ATP) were found suggesting an abnormality in energy metabolism, with an increase in the phosphodiester (PDE) peak. A follow up study 16 months later revealed reduction in size of the lesion on MRI and normal intracellular biochemistry by MRS. Four MS patients without visible superficial cerebral lesions showed no significant changes in phosphorus metabolism.

Adenosine Triphosphate↗
PubMed1991

Painful intraorbital meningiomas.

Three cases are reported of meningioma involving the orbital apex presenting with either progressive or episodic retroocular pain. In two cases pain was steroid responsive and in one of these patients this led to an initial diagnosis of orbital pseudotumour. Pain preceded visual loss and other symptoms by many months and these cases illustrate the importance of full investigation and where necessary surgical exploration in cases of apparent orbital inflammatory disease with an atypical or progressive course.

Adult↗
PubMed1991

Destructive lesions in demyelinating disease.

Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy.

Adolescent↗
PubMed1991

Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines.

Serial gadolinium enhanced MRI of the brain detects much clinically silent disease activity in early relapsing-remitting and secondary progressive multiple sclerosis (MS), and thus has an important role in monitoring the effects of therapy. Based on the proceedings of a recent Commission of the European Communities (CEC) workshop and a review of the literature, guidelines are presented for using MRI to monitor treatment trials in MS. The guidelines consider: A) MRI system and techniques; B) patient selection; C) trial design; D) analysis of results. Priorities for future research are also indicated.

Brain↗
PubMed1990

Neurological deterioration in young adults with phenylketonuria.

7 patients with phenylketonuria who developed neurological disability in adolescence or early adult life are described. 4 had been diagnosed by routine neonatal screening and started a low phenylalanine diet in infancy. 3 were diagnosed in early childhood because of developmental delay, and then started dietary treatment. Dietary control deteriorated in later years and was withdrawn in mid to late childhood. The late neurological deterioration cannot be directly ascribed to poor compliance with or cessation of dietary treatment in this small, retrospective study--but other likely causes have been excluded and 2 patients showed a striking clinical improvement when a strict diet was resumed. Serial magnetic resonance images from one of these patients show abnormalities that appeared after cessation of dietary treatment and resolved after diet was resumed. If these findings are confirmed, strict dietary control into adult life would be indicated for at least some patients with phenylketonuria.

Adult↗
PubMed1990

Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study.

OBJECTIVE: To compare the abnormalities shown by magnetic resonance imaging of the brain in three clinically distinct groups of patients with multiple sclerosis, and to correlate the extent of abnormality with the degree of clinical disability in the three groups. DESIGN: All patients underwent magnetic resonance imaging and full neurological examination, and their disability was scored according to the expanded Kurtzke disability state scale. SETTING: National Hospital for Nervous Diseases (Multiple Sclerosis NMR Research Group). PATIENTS: Three groups of patients with confirmed multiple sclerosis were studied: 12 patients with minimal disability despite a long (greater than 10 years) duration of illness (benign multiple sclerosis), 16 who had developed progressive disability after a relapsing and remitting course (secondary progressive multiple sclerosis), and 13 who had had progressive disability from the onset of the disease (primary progressive multiple sclerosis). MAIN OUTCOME MEASURES: Number and size of lesions in 17 anatomically defined sites; total lesion load, estimated with an arbitrary scoring system weighted for the size of lesions; and disability score. RESULTS: Magnetic resonance imaging showed that all 41 patients had abnormalities. These were extensive in the groups with secondary progressive and benign disease compared with the group with primary progressive disease. The lesions in the patients with secondary progressive disease were larger and more confluent than those in the two other groups (p = 0.007). Most lesions (85%) in the patients with primary progressive disease were under 5 mm in diameter; this percentage was higher than that in the two other groups (p = 0.032). Consequently the patients with primary progressive disease had the lowest mean lesion load (36.7); that in the patients with benign disease was 52.7 and that in the patients with secondary progressive disease 64.6 (p = 0.05). No correlation existed between disability and total lesion load. The distribution of brain lesions and of detectable lesions of the spinal cord, and the frequency of cortical atrophy, were similar in all groups. CONCLUSIONS: No relation was found between the degree of clinical disability and the extent of abnormality shown by magnetic resonance imaging: patients with clinically benign disease often had extensive abnormalities and those with primary progressive disease had surprisingly few lesions. Though magnetic resonance imaging increases knowledge of the disease process in multiple sclerosis and is invaluable in diagnosis, it is not helpful in predicting disability in individual patients.

Adult↗