Biomedical subjects
Publications and source records attributed to I Wilkinson.
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We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyperresponsiveness (PD20 methacholine < 8 mumol or a > 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P < 0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P = 0.03).
The BACTEC NR660 blood culture system, which uses infrared spectroscopy to detect carbon dioxide generated by bacterial growth, was compared with the new medium formulation of the Oxoid Signal system. Two trials were conducted: a comparative study of 88 organisms in simulated blood cultures and a clinical trial of 3,321 paired patient blood culture samples. Both trials showed that overall the BACTEC system performed better in the recovery of organisms. The Oxoid system was unable to detect by signal the growth of the majority of yeasts, nonfermentative gram-negative bacilli, Neisseria meningitidis, Nocardia spp., and Corynebacterium jeikeium. There were no significant differences in the yield of Staphylococcus spp., members of the family Enterobacteriaceae, Streptococcus spp., or anaerobic organisms. BACTEC detected growth more quickly than did the Oxoid system; 61% of the isolates were detected by BACTEC at 24 h, while 49% of the isolates were detected by Oxoid. The Oxoid system had a high proportion (58.5%) of false-positives, compared with 7.7% for the BACTEC system. Despite the new medium formulation of the Oxoid system, its performance is still not equivalent to that of the BACTEC system.
Three patients are described with different phenotypes and differing de novo interstitial deletions of the long arm of a chromosome 7. The first patient has a deletion with loss of the proximal 7q11.23 band. Only three other cases have been reported with this particular deletion. Our second case shows mild dysmorphism similar to the other four patients reported with deletion of bands 7q21.12----21.3. Our third patient has a deletion of the 7q22.1----32.2 segment and has many of the phenotypic features of the other reported cases of del 7q22----32. GUSB, the gene for beta-glucuronidase, has been localised to the 7cen----q22 region. Analysis of beta-glucuronidase levels in blood leucocytes of our patients has helped more precisely to assign this gene locus to 7q21.11 or 7q22.1.
Cytogenetic and coagulation studies have been performed on two patients with different abnormalities of chromosome 8, i.e. del(8p23.1----pter) and dup(8q23.1----qter). Results confirm the existence of a regulatory mechanism for clotting factor VII on chromosome 8 and define its location to the p23.1----p23.2 region.
The specific tolerance induced in mice by conjugates of human monoclonal IgG (HIgG) with monomethoxypolyethylene glycol (mPEG) was transferred to normal mice by spleen cells or a surface immunoglobulin negative (sIg-) Lyt-2+ subpopulation of these cells. Although transferable tolerance was demonstrable 6 to 14 days after treatment of the cell donors with tolerogen, the state of tolerance persisted in the treated mice for at least 43 days. Moreover, an extract prepared by freezing and thawing of the sIg- spleen cells obtained from mice 6 days after treatment with HIgG(mPEG)20 was capable of reducing (greater than 85%) the immune response of normal mice to heat aggregated HIgG. On the basis of these results, it is suggested that similar tolerogenic mPEG derivatives of xenogeneic monoclonal immunoglobulins (XIg) may prove to be useful therapeutic agents in man when administered before treatment with the unmodified XIg.
It is becoming apparent that the effectiveness of xenogeneic monoclonal antibodies (XIg), which are increasingly used for diverse therapeutic purposes in man, may be counteracted by their inherent immunogenicity. Since conjugates of proteins with monomethoxypolyethylene glycol (mPEG) have proved to be effective tolerogens in other systems, we have used an experimental model in mice to explore the tolerogenicity of mPEG conjugates of a human monoclonal IgG (HIgG), i.e. a myeloma protein. Administration of these conjugates prior to immunization with heat aggregated HIgG (ha-HIgG) resulted in specific tolerance, as manifested by a marked reduction in the level of antibodies to HIgG, which was related to the degree of conjugation and the dose of conjugate administered. Thus, administration of HIgG(mPEG)20 6 to 43 days prior to immunization with ha-HIgG resulted in an inhibition of anti-HIgG antibody formation of the order of 85-90%, in relation to the titres of mice receiving PBS in lieu of HIgG(mPEG)20; these results hold the promise that mPEG conjugates of XIg may prove therapeutically useful in man in relation to organ transplantation, localization of tumours by immuno-imaging and tumour destruction by immunotoxins.
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The effect of dietary xylitol on the ability of the rat caecal flora to metabolise xylitol was investigated. Xylitol metabolism in micro-organisms has generally been assessed in terms of pH change and acid production which are often insensitive in demonstrating low rates of substrate utilisation. Using a rapid and sensitive radioisotopic assay, in which 14CO2 production from [U-14C] xylitol was measured, it was possible to show that the caecal microflora obtained from rats can metabolise xylitol. This activity was increased 10, 15, 30 and 40-fold in the caecal flora taken from rats fed diets containing 2.5,5,10 and 20% xylitol, respectively. Using the caecal microflora of normally fed rats, the order of 14CO2 production from 14C-labelled sugars and sugar alcohols was glucose greater than fructose greater than xylose greater than sorbitol greater than or equal to xylitol. The feeding of glucose and fructose did not alter the 14CO2 producing activities, whereas xylose feeding increased xylose metabolism, sorbitol feeding increased sorbitol and xylitol metabolism, xylitol feeding increased sorbitol, xylose and its own metabolism and arabitol feeding increased xylose and sorbitol metabolism. Marked changes were also observed in the population of the caecal flora of xylitol-fed rats, with increases in the number of gram-positive bacteria, compared to rats on a normal diet. Possible mechanisms for these effects involve mutation, selection of micro-organisms capable of metabolising sugar alcohols, and the induction of enzymes involved in sugar alcohol metabolism.
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