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Biomedical subjects

T Gibson

Publications and source records attributed to T Gibson.

At least 91 records · Page 5Linked to original sources

Monoclonal antibody treatment in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody.

Six patients with rheumatoid arthritis were treated with a CD7 mouse monoclonal antibody, RFT2, daily for 15 days. Only two patients had a significant improvement in clinical disease activity which lasted 7-14 days. No serious adverse effects occurred although all patients developed antibodies against mouse immunoglobulin. During treatment T-lymphocyte numbers decreased and T-lymphocyte CD7 expression was absent in all but one patient.

Adult↗

Season of birth in schizophrenia. Evidence for confinement of an excess of winter births to patients without a family history of mental disorder.

Although it is well recognised that schizophrenic patients are more often born in winter, the significance of this finding remains obscure. Data relating to season of birth and family history were analysed for 561 patients with an ICD-9 diagnosis of schizophrenia. Patients with no family history of any psychiatric disorder group were significantly more likely to be born in winter than patients with a first-degree relative affected by schizophrenia. In comparison with normal population controls, only those without a family history exhibited a significant excess of winter births, suggesting an environmental factor of greater aetiological significance in these patients.

Cross-Sectional Studies↗

Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1.

Leukocyte adhesion receptors on endothelial cells play an important role in the evolution of synovitis. We studied sequential synovial biopsies at Weeks 0, 2 and 12 in 11 patients with rheumatoid arthritis beginning parenteral gold therapy either alone or combined with 120 mg intramuscular methylprednisolone acetate at Weeks 0, 4 and 8 of treatment. Expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) decreased on synovial blood vessels after both 2 and 12 weeks treatment (p less than 0.05), while the overall vascularity of the synovium did not change. Neutrophil numbers within the synovial membrane also decreased although this did not reach statistical significance. In contrast, there was no significant change in numbers or subset distribution of T cells or in Class II MHC expression by synovial lining cells, mononuclear cells or endothelial cells. Our results suggest that one of the early effects of intramuscular gold and glucocorticoid therapy may be a downregulation of the acute inflammatory process associated with the endothelial expression of a neutrophil adhesion receptor and the subsequent recruitment of neutrophils into the joint.

Adolescent↗

A regular pattern of two types of 100-residue motif in the sequence of titin.

Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle. Its molecules are string-like and in vivo span from the M to Z-lines. I-band regions of titin are thought to make elastic connections between the thick filament and the Z-line, thereby forming a third type of sarcomere filament. These would centre the A-band in the sarcomere and provide structural continuity in relaxed myofibrils. The A-band region of titin seems to be bound to the thick filament, where it has been proposed to act as a 'molecular ruler' regulating filament length and assembly. Here, we show that partial titin complementary DNAs encode a regular pattern of two types of 100-residue motif, each of which probably folds into a separate domain type. Such motifs are present in several evolutionarily divergent muscle proteins, all of which are likely to interact with myosin. One or both of the domain types is therefore likely to bind to myosin.

Amino Acid Sequence↗

Solution structure of the DNA-binding domain of the yeast transcriptional activator protein GCN4.

The solution structure of an active synthetic peptide containing both the leucine zipper and the adjacent basic domain of the yeast transcription factor GCN4 (residues 220-280) was determined by NMR. The two domains show structurally distinct behaviours. In the absence of DNA, the basic domain is, although very flexible, structured and fluctuating around a helical conformation. The leucine zipper region forms a long, uninterrupted helix. From a suitable set of NMR distances the three-dimensional structure of the leucine zipper monomeric sub-domain was calculated by distance geometry algorithms. The structure of the symmetrical parallel dimer was obtained by model building using the NMR information. A smaller peptide with the sequence of the isolated basic region (residues 1-35 of the 61 residue peptide) was also synthesized. Circular dichroism studies showed 30-40% helicity. A flexible helix spans the region between residues 8 and 21. The comparison of our results with suggested models is discussed in detail.

Algorithms↗

A controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect.

Sixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a randomized double-blind controlled trial for 48 weeks. There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessments. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period (four active, eight placebo). Side effects were reported more commonly in the sulphasalazine group (27 versus 17, NS), but only 21 patients stopped treatment because of side effects (12 versus 9, NS). Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo. We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis.

Chronic Disease↗

Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: a 24-week randomized controlled trial.

Fifty-nine patients commencing intramuscular sodium aurothiomalate therapy were randomized to receive three doses of 120 mg intramuscular depot methylprednisolone acetate or matching placebo at weeks 0, 4, and 8 in addition to chrysotherapy. The group receiving methylprednisolone had more rapid disease improvement. This advantage persisted for up to 12 weeks, although by 24 weeks both groups exhibited similar benefits due to continued improvement in the group treated with gold alone. Withdrawals secondary to gold-induced side-effects occurred later in the steroid group (median time to withdrawal: 15 weeks steroid; 4.5 weeks placebo, P less than 0.05), and there were fewer withdrawals due to a lack of effect in the steroid group (one steroid versus three placebo, P NS). We conclude that glucocorticoids given as intermittent, intramuscular depot injections have a significant short term benefit which can be maintained by concomitant administration of intramuscular gold.

Adolescent↗

The phototrophic bacterium Rhodopseudomonas capsulata sp108 encodes an indigenous class A beta-lactamase.

The nucleotide sequence of a 2.37 kb DNA fragment derived from cloning a total DNA digest of Rhodopseudomonas capsulata sp108 was determined. The DNA codes for a beta-lactamase, a protein showing sequence similarity to the ampR protein of Enterobacter cloacae and an unidentified open reading frame. Hybridization experiments with a probe carrying DNA from within the beta-lactamase gene suggests a chromosomal location for the coding sequences in strain sp108 and in sp109, a penicillin-sensitive revertant of sp108 in which the enzyme is not inducible. A protein-sequence comparison of the deduced amino acid sequence of the Rps. capsulata beta-lactamase indicates that it is a Class A enzyme and that its sequence can be aligned with those of the characterized beta-lactamases from Staphylococcus aureus, Bacillus licheniformis and the Escherichia coli plasmid (R-TEM enzyme), with only a few insertions or deletions. The corresponding DNA sequence is, however, characteristically rhodopseudomonad, suggesting that it is not a recently transposed gene.

Amino Acid Sequence↗

Outpatient lumbar epidural corticosteroid injection in the management of sciatica.

The value of epidural injections of corticosteroid as an outpatient treatment of sciatica has been hitherto uncertain. An epidural injection of 80 mg methylprednisolone in 10 ml physiological saline was compared with an interspinous injection of 2 ml physiological saline in a double blind fashion amongst 39 outpatients. Significant differences of pain relief were seen between the two groups within 2 weeks. This benefit disappeared for six (35%) patients within 6 months of treatment although 11 (65%) successfully treated subjects had sustained improvement up to this time. Outpatient epidural injections of corticosteroid are thus a useful short-term means of relieving pain in sciatica but probably have little effect on the long-term natural history of symptoms. Factors associated with a failure to respond to epidural steroid injections are discussed.

Adrenal Cortex Hormones↗