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D J Ward

Publications and source records attributed to D J Ward.

At least 55 records · Page 3Linked to original sources
PubMed1987

Computer-aided design and physiological testing of a luteinising hormone-releasing hormone analogue for 'adjuvant-free' immunocastration.

An analogue of LHRH containing an extension of Gly-Cys at the carboxyl-terminus has been designed to permit reproducible coupling to a suitably modified carrier via a thioether bond. Potential energy calculations indicated that this analogue adopted a conformation in solution virtually identical to the type II' turn around Gly-6-Leu-7 predicted for native LHRH. Intradermal administration of a conjugate of this analogue with purified protein derivative of tuberculin to male rats previously primed with BCG vaccine rapidly led to complete testicular regression. This adjuvant-free immunisation protocol may represent an alternative to castration for the veterinary control of reproductive function.

Animals↗
PubMed1987

Carbamazepine-induced facial burns caused by a photocopier.

A 36-year-old woman on long-term anticonvulsant therapy with carbamazepine (Tegretol) sustained superficial facial and corneal burns after using a photocopier for 2 h. Photosensitivity is a rare side-effect of carbamazepine therapy, and progression to a superficial burn has not been reported previously. Photocopiers emit a very low level of ultraviolet irradiation: this would not cause burns in a normal patient but could possibly do so in someone who is sensitive to ultraviolet light.

Adult↗
PubMed1987

Comparative conformation-activity relationships for hormonally- and centrally-acting TRH analogues.

Empirical energy calculations have been applied to a series of thyrotrophin-releasing hormone (TRH) analogues in an attempt to incorporate the conformational parameter into traditional Quantitative Structure-Activity Relationships (QSAR). A search was made of the potential surface of each analogue using a SIMPLEX technique coupled with a model representing solvent effects as a dielectric continuum. Conformers of TRH can be described in terms of the distance between the pyroglutamyl, imidazole and prolyl rings, and presented as two-dimensional descriptor coordinates using multidimensional scaling. This process was repeated for stable and metastable conformers of all the TRH analogues investigated and correlated with experimental data on receptor affinity, relative stability and biological potency of the analogues. The results obtained suggest that modifications to the TRH structure can lead to greater potency in addition to improved stability, and that providing the appropriate theoretical approach is taken, it is possible to apply QSAR-based design procedures to conformationally-flexible drugs.

Animals↗
PubMed1986

Conformational study of thyrotrophin-releasing hormone. I. Aspects of importance in the design of novel TRH analogues.

The solution conformations of thyrotrophin-releasing hormone (TRH), a biologically-active tripeptide, have been predicted computationally using a method which represents solution effects as a dielectric continuum surrounding the molecule throughout energy minimisation; this is described as the reaction field contribution. The predicted conformations have been compared with previous experimental and theoretical studies. Favoured conformations of TRH under other simulated conditions have also been examined, including the behaviour of the cis isomer, and have been related to possible interactions with intermediates and with specific receptors. The relevance of these predictions to the design of biologically-active analogues of TRH has been analysed.

Hydrogen-Ion Concentration↗
PubMed1985

Patterns of antihistone antibody specificity in systemic rheumatic disease. I Systemic lupus erythematosus, mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis.

A new fluorimetric assay was used to measure the relative amounts of antibodies to individual nuclear histones in sera from 102 patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis. In SLE sera, the predominant responses were to histones H-1, H-2B, and H-3, with marked elevations of binding to H-1 and H-2B in one-third of the patients, and to H-3 in one-fourth; antibodies of both the IgG and IgM classes were also detected. In a few SLE sera, the pattern of histone response differed or was restricted to 1 immunoglobulin class. In mixed connective tissue disease, only 2 of 9 sera showed elevated histone binding activity, the response being predominantly to H-3 in 1 patient and to H-1 and H-2B in the other. Binding to H-2B was also prominent in 2 of 3 patients with primary sicca syndrome. The highest antihistone reactivity and the most heterogeneous response patterns were observed in patients who had rheumatoid arthritis with vasculitis; 6 of 8 of those sera had elevated histone reactivity. In SLE, the highest histone binding results were found among patients with a history of photosensitivity. Histones are closely associated with DNA in the nucleosome, and we speculate that antihistone antibodies could arise as a result of damage to DNA, induced by drugs or irradiation.

Antibodies↗
PubMed1984

Acral lentiginous melanoma: an illustrative case report and brief review of the literature.

Acral lentiginous melanoma has not previously been reported in the English literature. It is a rare tumour occurring nearly always on the palmar and plantar surfaces and has only recently been recognised as a separate histological group of melanoma. Diagnosis can be difficult both clinically and histologically, and is often delayed. An illustrative case is presented and the world literature is briefly reviewed.

Female↗
PubMed1984

A double-blind study comparing the effectiveness of cromolyn sodium and sustained-release theophylline in childhood asthma.

The effectiveness of cromolyn sodium and theophylline on asthma in children was compared during a 3-month trial. Forty-six children (aged 5 to 15 years) with asthma were assigned at random to cromolyn or theophylline (Theo-Dur) treatment groups. Each subject received theophylline placebo or cromolyn placebo in addition to the active drugs. A methacholine challenge test was done at the start of the study to document asthma and was repeated during the third month. The theophylline dosage was regulated to obtain serum levels of 10 to 15 micrograms/mL by a physician not involved directly with patient care. Forty patients completed the study. Both theophylline and cromolyn treatment groups showed improvement from base-line status in terms of symptom scores, pulmonary function, and decreased use of inhaled albuterol. Patients treated with theophylline had more side effects and required more frequent office visits than those treated with cromolyn. Both groups had decreased sensitivity to methacholine, and for one statistical test patients treated with cromolyn improved significantly. These results indicate that cromolyn is as effective as theophylline in treating mild to moderate asthma in children; additional benefits were fewer side effects and a possible decrease in bronchial hyperactivity.

Adolescent↗
PubMed1983

A fluorimetric assay for human antibodies to all the histones.

We describe a fluorescence immunoassay for anti-histone antibodies in human sera. Histones are bound to immobilised tyrosine-glutamic acid copolymer on a polystyrene cuvette. With mixed histones as antigen normal sera showed low levels of antibody binding. Much higher values were obtained with some sera from rheumatoid arthritis (RA) patients positive for antinuclear antibodies, and from patients with vasculitic RA, systemic lupus erythematosus (SLE) and drug induced LE. Antibodies to all 5 individual histones were elevated in SLE and vasculitic RA patients. Preliminary results suggest that differences in response patterns may be disease related.

Antibodies, Antinuclear↗
PubMed1983

Gallium 67 scanning in rheumatoid arthritis.

Gallium 67 scans were performed on both knees of 38 patients with rheumatoid arthritis. There was a significantly higher level of 67Ga accumulation in those knees with clinically active synovitis (p less than 0.001). Synovial white cell concentration was also elevated in the group with active synovitis. The white cell concentration correlated with the 67Ga knee/femoral ratio at the p less than 0.001 level. 67Ga activity in the synovial fluid was predominantly in the supinate and activity was also present in the synovium. The findings indicate that 67Ga uptake occurs in rheumatoid joints and reflects the degree of synovial inflammation.

Arthritis, Rheumatoid↗
PubMed1981

A clinico-pathological study of fatal pulmonary embolism in a specialist orthopaedic hospital.

A study of post-mortem examinations performed between 1970 and 1979 at a specialist orthopaedic hospital revealed that the overall mortality rate due to pulmonary embolism was 0.23% and that pulmonary embolism was responsible for 19.1% of hospital deaths. The majority of these fatalities occurred following operation for either fractured proximal femur or total hip replacement. During the decade, 928 patients were operated upon for fractured proximal femur, none received prophylactic anticoagulation therapy and the mortality rate due to pulmonary embolism was 17.7%. However, the yearly mortality rate decreased with time and this change was attributed to earlier operation and early mobilisation. Over the same period, 3016 patients underwent total hip replacement, 20% were anticoagulated prophylactically; the mortality rate due to pulmonary embolism was 0.63%. In those patients who died of pulmonary embolism, post-mortem evidence of deep vein thrombosis was usually found, but no relationship between site of thrombosis and side of operation was observed. Pulmonary embolism was diagnosed in only a few patients although on later consideration at least a third of patients had symptoms suggestive of previous emboli. Possible improvements in diagnosis are discussed and a more rational approach to prophylactic anticoagulation suggested.

Dextrans↗