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Biomedical subjects

J Webb

Publications and source records attributed to J Webb.

At least 163 records · Page 9Linked to original sources
PubMed1987

Structural requirements of DNA used in the Farr assay to detect antibodies directed against double-stranded DNA.

The measurement of antibodies to DNA in SLE requires the use of double-stranded DNA (dsDNA), demonstrably free of single-stranded regions. Such dsDNA preparations can, however, contain other structural components. In this study DNA preparations with defined structure, both secondary (single- and double-stranded and random base-paired) and tertiary (superhelical and open circular), were used in the Farr assay to measure the DNA binding of sera from patients with SLE and related connective-tissue diseases. The presence of true single-stranded DNA regions in denatured DNA, native DNA, and dsDNA containing single-stranded regions increased the DNA binding measured in all sera. DsDNA, whether intact or containing small regions of random base-pairing, was bound by sera from the majority of patients with SLE but not by non-SLE sera. Superhelical dsDNA from bacteriophage PM2 was bound by SLE sera to a greater extent than linear dsDNA was. Inhibition experiments suggested that this difference in binding to DNA according to tertiary, as opposed to secondary, structure is because there are fewer available binding sites on superhelical dsDNA. DNA binding, as measured by the Farr assay, can thus be influenced by both secondary and tertiary DNA structure. Using superhelical DNA, advantage can be taken of the dsDNA form plus tertiary structure to enhance DNA binding of SLE sera beyond the levels achieved using linear dsDNA.

Antibodies, Antinuclear↗
PubMed1987

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Animals↗
PubMed1987

Interstitial lung disease as the presentation of anti-Jo-1 positive polymyositis.

A patient presenting with interstitial lung disease was predicted to have underlying polymyositis when found to be anti-Jo-1 antibody positive. When myopathy developed later with elevated serum creatine phosphokinase and myoglobin levels, the electromyogram was nonmyopathic, and polymyositis was confirmed by muscle biopsy. The case illustrates the value of anti-Jo-1 as a 'marker' autoantibody for polymyositis, and the need for thorough investigation of patients with interstitial lung disease of uncertain etiology. This should include indirect immunofluorescence using a dividing cell substrate and tests for antibodies to extractable tissue antigens. The need to completely evaluate patients with dermatopolymyositis is also emphasised.

Aged↗
PubMed1987

Concurrence of rheumatoid arthritis and systemic lupus erythematosus: report of 11 cases.

The concurrence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) has been reported infrequently. Eleven patients are described here with both RA and SLE, in whom the diagnoses were separated by one to 24 years. Because of the difficulty in diagnosing RA occurring subsequent to SLE, only patients with classical RA as their initial diagnosis were included. Further difficulties arise because arthritis is common to both diseases and may be deforming in SLE, antinuclear antibodies (ANA) are not uncommon in RA, and rheumatoid factor (RF) may be seen in SLE. Nonetheless, judicious application of the American Rheumatism Association (ARA) criteria allows both diagnoses to be made in the individual patient. In our patients there was erosive arthritis in nine, rheumatoid nodules in five, and urinary abnormalities in 10. Serological evidence of RA and SLE with positive RF and ANA and raised DNA antibodies was universal, all patients had haematological evidence of SLE, and all but one decreased serum complement levels. These cases suggest that the concurrence of RA and SLE is not as rare as previously considered and may occur more often than expected by chance alone.

Adult↗
PubMed1987

Benign joint hypermobility with neuropathy: documentation and mechanism of tarsal tunnel syndrome.

Eleven consecutive patients with tarsal tunnel syndrome were reviewed. All had pes planus, 8 had calcaneal valgus hindfoot, and generalized benign joint hypermobility syndrome was evident in 9. Detailed enquiry was necessary to identify apparently trivial precipitating events. In 6 patients there was superimposed secondary reflex sympathetic dystrophy which tended to obscure symptoms of the causative tarsal tunnel syndrome. Wider recognition of this cause-effect mechanism and early management with orthotic footwear and intrinsic foot muscle exercises may obviate the need for surgical intervention in many cases.

Exercise Therapy↗
PubMed1986

Hydatidiform mole in England and Wales 1973-83.

The number of cases of hydatidiform mole (HM) registered annually in England and Wales has risen since 1973 to 1.54 per 1000 live births in 1983. For women over 50 the risk per pregnancy was 411 times and for girls under 15 it was six times greater than that for women aged 25-29. 7.75% of patients had chemotherapy for invasive mole or choriocarcinoma. Patients who had had oxytocin-induced or prostaglandin-induced uterine evacuation or hysterotomy were more likely to need chemotherapy. Human chorionic gonadotropin (HCG) was undetectable by 56 days after evacuation in 42% of patients, none of whom required chemotherapy; a considerable reduction in follow-up time for this subgroup is proposed. For patients whose HCG values became normal more than 56 days after evacuation and stayed normal for 6 months the risk of recrudescent disease was 1 in 286. In subsequent pregnancies the risk of a second HM was 1 in 76 and that of a third was 1 in 6.5. 11 (0.2%) patients died, 2 from drug-resistant choriocarcinoma.

Adolescent↗
PubMed1986

Mössbauer spectroscopic studies of the cores of human, limpet and bacterial ferritins.

Ferritin cores from human spleen, limpet (Patella vulgata) haemolymph and bacterial (Pseudomonas aeruginosa) cells have been investigated using 57Fe Mössbauer spectroscopy. The Mössbauer spectra were recorded over a range of temperatures from 1.3 to 78 K, all the spectra are quadrupole-split doublets with similar quadrupole splittings and isomer shifts, characteristic of iron(III), while at sufficiently low temperatures the spectra of all the samples show well-resolved magnetic splitting. At intermediate temperatures, the spectra from the human ferritin exhibit typical superparamagnetic behaviour, while those from the bacterial ferritin show behaviour corresponding to a transition from a magnetically ordered to a paramagnetic state. The spectra from the limpet ferritin show a complex combination of the two effects. The results are discussed in terms of the magnetic behaviour of small particles. The data are consistent with magnetic ordering temperatures of about 3 and 30 K for the bacterial and limpet ferritin cores, respectively, while the data indicate that the magnetic ordering temperature for the human ferritin cores must be above 50 K. These differences are interpreted as being related to different densities of iron in the cores and to variations in the composition of the cores. The human ferritin cores are observed to have a mean superparamagnetic blocking temperature of about 40 K, while that of the limpet ferritin cores is about 25 K. This difference is interpreted as being due not only to different mean numbers of iron atoms in the two types of core but also to the higher degree of crystallinity in the cores of the human ferritin.

Animals↗
PubMed1986

Measurement of serum DNA binding in chronic active hepatitis and systemic lupus erythematosus using the Farr assay.

Antibodies to double-stranded DNA (dsDNA), generally regarded as highly specific for systemic lupus erythematosus (SLE), have also been reported in chronic active hepatitis (CAH). Using the Farr assay and E. coli DNA, fractionated by benzoylated-naphthoylated-DEAE cellulose chromatography into dsDNA and dsDNA containing single-stranded regions, we compared the serum DNA binding of CAH and SLE patients. Although CAH sera were found to have dsDNA binding significantly above the normal control group such binding was of low level and we could find no evidence of markedly elevated dsDNA binding in CAH. However 12 of the 20 CAH sera studied did bind preferentially to dsDNA containing single-stranded regions suggesting the presence of anti-single-stranded DNA antibodies. We conclude that the description of elevated anti-dsDNA antibodies, as measured by the Farr assay, in CAH is due to the interaction of anti-single-stranded DNA antibodies or other serum components with single-stranded DNA contaminating dsDNA preparations.

Adult↗
PubMed1986

Complement and immune complex diseases.

Research during the past decade has led to a much greater understanding of the activation and control, as well as a more complete delineation, of the complement system of proteins. There has been definition of the roles of individual components in modulation of immune complex formation, the deposition of which leads to tissue injury in the autoimmune connective tissue diseases. The ability of serum to render immune complexes more soluble is complement-mediated and appears to be an important protective mechanism against immune complex diseases. Inherited deficiencies and production of non-functional variants of complement components, decreased synthesis, hypercatabolism, and the presence of serum inhibitors may all contribute to the reduced immune complex solubilisation which has been found in the connective tissue diseases. More work is required to define further the role of complement and immune complexes in the basic pathogenesis of these diseases.

Antigen-Antibody Complex↗
PubMed1986

Cytophagic panniculitis.

A 60 year old woman developed generalised erythema nodosum-like lesions together with hectic fever, lymphadenopathy, and hepatitis. Biopsies revealed lobular panniculitis with a benign histiocytic infiltrate and prominent phagocytosis in subcutaneous sites, lymph nodes, and bone marrow. All immunological, serological, and culture studies were negative, apart from throat isolation of herpes simplex. The patient responded to high-dose corticosteroids. The case illustrates the differential diagnosis of lobular panniculitis, with histiocytic infiltrate and cytophagocytosis. These combined features are consistent with the recently described syndromes of cytophagic panniculitis and virus-associated hemophagocytic syndrome.

Erythrocytes↗
PubMed1986

Inhibition of complement-mediated solubilisation of antigen-antibody complexes by serum factor(s) in patients with various connective tissue diseases.

Control of immune complex formation is important to limit disease resulting from their deposition in tissues. Any inhibition of immune complex solubilisation is thus significant in the pathogenesis of immune complex diseases. More than half of our patients with various rheumatic connective tissue diseases were demonstrated to have serum inhibition of immune complex solubilisation (12/16 rheumatoid arthritis, 22/37 systemic lupus erythematosus, 16/29 primary Sjogren's syndrome, and eight of nine with mixed connective tissue disease). This serum inhibitory activity did not correlate well with serum levels of IgM rheumatoid factor or circulating immune complexes, and its nature remains to be elucidated.

Antibodies, Antinuclear↗
PubMed1986

Calcification is rare in adult-onset dermatopolymyositis.

Extensive subcutaneous and muscular calcification developed in a patient having adult-onset dermatopolymyositis (DM-PM) with an 'overlap' connective tissue disease. We wish to emphasize the rarity of calcification in adult onset DM-PM, which is contrary to the generally held impression.

Adult↗