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Biomedical subjects

M W Turner

Publications and source records attributed to M W Turner.

At least 91 records · Page 5Linked to original sources

The importance of antibody quality in sandwich ELISA systems. Evaluation of selected commercial reagents.

The detection of low levels of immunoglobulin in cell culture supernatants etc. by ELISA procedures demands high sensitivity and absolute specificity. We have used commercially available antibodies prepared by positive affinity purification and immunoglobulin fractions obtained by ion-exchange chromatography in various combinations in ELISA systems for such quantitative analyses. These demonstrate that when affinity-purified reagents lacking unwanted anti-species cross-reactivity are used as both the capture antibody and the indicator antibody the results are markedly superior (high sensitivity, low backgrounds and a wide working range) compared to those obtained with all other possible combinations.

Antibodies, Anti-Idiotypic↗

Dyazide-induced reversible acute renal failure associated with intracellular crystal deposition.

Acute interstitial nephritis due to Dyazide therapy, ie, a combination of hydrochlorothiazide (25 mg) and triamterene (50 mg), has been recently reported in the literature. This had been characterized by nonoliguric renal failure after a long latent period (weeks) following exposure to the drug. Pathologic data have indicated a drug-induced hypersensitivity reaction. We report here one case of oliguric acute renal failure after a massive Dyazide intoxication. Based on the results of the renal biopsy and clinical course, we propose that the oliguria was secondary to a direct toxic effect on the tubules, and intrarenal obstruction was secondary to triamterene crystals and crystal-laden cells. In addition, pathologic findings also suggested a moderate hypersensitivity reaction. After hemodialysis and short-term steroid therapy, the patient achieved complete recovery of renal function within 12 days. Recent knowledge of triamterene-induced nephrolithiasis helps to explain the pathogenesis of acute renal failure in this patient, and is briefly reviewed here.

Acute Kidney Injury↗

Increased intestinal permeability in atopic eczema.

We have investigated gastrointestinal permeability in children with atopic eczema by measuring the relative urinary excretion rates of the inert di- and monosaccharides lactulose and rhamnose following their oral administration. The median lactulose/rhamnose ratio was greater in 26 children with atopic eczema than in a control group of 29 children which included both healthy individuals and others with various noneczematous dermatoses. This increased permeability may be a primary abnormality of the gut or may reflect intestinal mucosal damage caused by local hypersensitivity reactions to food antigens.

Adolescent↗

Evaluation of C3b/C3bi opsonization and chemiluminescence with selected yeasts and bacteria using sera of different opsonic potential.

C3 fragment opsonization and chemiluminescence were assessed using two yeasts (Saccharomyces cerevisiae and Candida albicans) and two strains of bacteria (Staphylococcus aureus and Escherichia coli) following incubation with sera previously shown to be either efficient or poor in the opsonization of baker's yeast. Sera with poor function consistently fixed lower levels of C3 fragments and generated less chemiluminescence with all four organisms than sera with normal function. The differences were most marked with the two yeasts. We conclude that sera with normal complement function but manifesting a relatively common defect in the opsonization of baker's yeast have a general opsonic defect.

Adult↗

The role of opsonins in vacuolar sealing and the ingestion of zymosan by human neutrophils.

After opsonization with whole human serum, with IgG antibody alone or with C3 fragments alone, the ingestion of zymosan particles by human neutrophils was found to correlate most closely with the efficiency of C3 fragment deposition on the zymosan surface. Selective opsonization of zymosan particles with IgG did not promote phagocytosis at all in suspension, but could promote ingestion after particle-cell contact was induced by centrifugation. In contrast, zymosan particles in suspension selectively opsonized by C3 fragments were ingested as efficiently as those opsonized with whole serum, and we suggest that C3 fragments provide the principal stimulus for phagocytosis of zymosan. The process of vacuolar sealing was not dependent on the state of opsonization of the particles and was significantly more efficient with unopsonized particles, indicating that formation of unsealed vacuoles is not due to a failure of the 'zipper' mechanism of sequential interaction of cell surface receptors and opsonic ligands.

Adult↗

A prospective study on the impact of the renal biopsy in clinical management.

A three year prospective study involving 80 patients was conducted to assess the impact of renal biopsy on clinical management. Pre-biopsy predicted histologic diagnosis was changed in 35 (44%) of the patients as a result of the biopsy. Prognosis changed in 45 (57%) of the patients. Therapy changed in 25 (31%) of the patients. These results suggest that, overall, renal biopsy had a marked effect on management. However, we identified subgroups of patients who were unlikely to have their management changed as a result of the biopsy: of 16 patients with a pre-biopsy diagnosis of IgA nephropathy, 1 (6%) had treatment changed because of the biopsy; and of the 50 patients without heavy proteinuria (greater than 3 g/24 h), 10 (20%) had treatment changed because of the biopsy. Although our overall results suggest an important role for renal biopsy in clinical management, renal biopsy has the least apparent impact in patients with a pre-biopsy diagnosis of IgA nephropathy or without heavy proteinuria.

Biopsy↗

Angiography and complement activation. Evidence for generation of C3a anaphylatoxin by intravascular contrast agents.

The potent anaphylatoxin C3a was measured in the peripheral blood of eleven patients receiving radiocontrast agents whilst undergoing coronary angiography. In seven patients C3a levels were raised during this procedure and in three of these the anaphylatoxin was increased between four and tenfold. In four patients C3a levels remained within the normal range. In vitro tests of five contrast agents revealed marked heterogeneity in their ability to generate C3a from serum.

Anaphylatoxins↗

Complement activation and anaphylactoid response to protamine in a child after cardiopulmonary bypass.

A 2 1/2 year old boy had a sudden, severe, and unexpected anaphylactoid reaction after an otherwise uncomplicated repair of a partial atrioventricular septal defect. The reaction, comprising haemorrhagic pulmonary oedema and peripheral circulatory collapse, followed neutralisation of heparin by protamine. Measurements of serum complement (C3 and C4) concentrations suggested that a pronounced consumption of complement occurred during the adverse response.

Anaphylaxis↗

Suboptimal C3b/C3bi deposition and defective yeast opsonization. I. Evidence for the absence of essential co-factor activity.

Defective yeast opsonization in sera with no demonstrable abnormality of known complement components is associated with the absence of inactivity of a co-factor which enhances the deposition of C3 fragments (C3b/C3bi) derived from both classical and alternative pathways of complement activation. The factor binds strongly to zymosan at 4 degrees C and loses its biological activity completely when heated for 30 min at 56 degrees C but not when similarly heated at 50 degrees C. Sera with defective deposition of C3 fragments may be readily corrected with small quantities of sera having normal function. Sera with the defect do not correct other similar sera.

Adult↗

Suboptimal C3b/C3bi deposition and defective yeast opsonization. II. Partial purification and preliminary characterization of an opsonic co-factor able to correct sera with the defect.

Using a correction assay a factor essential for normal deposition of C3 fragments on zymosan was identified in fractions of serum obtained by Sephacryl S-300 gel filtration (eluting between IgG and albumin), preparative Pevikon block electrophoresis (eluting in the beta-region) and DEAE-ion-exchange chromatography (eluting immediately post IgG). Active material was also identified in a commercial preparation of transferrin. A combination of DEAE-ion-exchange chromatography and gel filtration was used to partially purify the co-factor. The factor has an approximate relative molecular mass of 70,000-80,000.

Chromatography, Gel↗

Intestinal sugar permeability: relationship to diarrhoeal disease and small bowel morphology.

The permeability of the intestine was studied in 39 children (1 month to 3 years of age) with diarrhoea and in 28 children (6 months to 15 years of age) undergoing duodenal biopsy. Permeability was measured by differential absorption from an isotonic oral load containing 3.5 g lactulose, 0.5 g L-rhamnose, 0.5 g D-xylose, and 5 g lactose. Urinary sugar excretion was determined by quantitative thin-layer chromatography. Children with acute gastroenteritis had a greatly increased permeability, with a mean lactulose/L-rhamnose excretion ratio of 0.43 +/- 0.31 (normal less than 0.07). Children retested 3-16 weeks after complete recovery of their gastroenteritis had normal permeability (0.045 +/- 0.018). Children with chronic diarrhoea also had an increased permeability (0.12 +/- 0.074), but significantly less than the acute gastroenteritis group (p less than 0.01). Abnormal proximal small bowel morphology was associated with increased permeability, and a strong correlation between crypt depth and permeability was observed (r = 0.66, p less than 0.001). Abnormal intestinal permeability was associated with diarrhoeal disease and with mucosal damage. It appears to be a reliable and useful index of mucosal integrity.

Adolescent↗

A controlled trial of hyposensitization with adsorbed tyrosine Dermatophagoides pteronyssinus antigen in childhood asthma: in vivo aspects.

Continuing study for a second year and further analysis of a double-blind placebo controlled trial, already briefly reported, of injections of tyrosine-adsorbed, glutaraldehyde-modified Dermatophagoides pteronyssinus antigen in fifty-one children with perennial asthma and positive bronchial challenge to the antigen, confirms that the patients receiving the treatment reduced their symptomatic medication more than controls, without deterioration of symptoms. Some became symptom-free, when off all treatment. A double-blind placebo controlled trial of continuing treatment for a second year gave evidence of deterioration when the treatment was stopped. Within the treatment group, the improvement was associated with loss of late (6 hr) reaction to bronchial provocation with the antigen, but was not associated with change of immediate (20 min) reaction in lungs or skin. Those who improved in the placebo group did not lose their late reaction. There was a trend for similar benefit from active treatment in the control group, during the second year, though less than in the original active group, and only one lost his late reaction. Only one of the six children with very severe early onset asthma improved. Local reactions to either active or placebo (tyrosine) were seen in half the patients; these were mild and did not influence the treatment. Systemic symptoms occurred shortly after four active injections and after two placebo injections; only one patient stopped the treatment.

Adolescent↗

In vitro investigations in asthmatic children undergoing hyposensitization with tyrosine-adsorbed Dermatophagoides pteronyssinus antigen.

Successful hyposensitization to Dermatophagoides pteronyssinus in perennial childhood asthma was associated with a slight mean rise of serum IgG antibody to the mite antigen in contrast to a placebo group in whom this antibody fell slightly. No relationship was detected between the effect on asthma and the magnitude of this change. Nor was there any consistent effect on IgE or IgA antibody. There was a wide range of total serum IgE and IgE, IgG and IgA antibody to D. pteronyssinus before treatment; this level did not predict the effect of treatment. Some patients lacked IgA antibody. IgE antibody to timothy grass pollen was raised in some but not others. These levels did not change systematically during the study and improvement occurred in those who had this antibody as well as IgE antibody to D. pteronyssinus. IgG and IgE antibodies to D. pteronyssinus were significantly correlated in the pre-treatment samples. Lymphocyte thymidine uptake was lower after 8 weeks of treatment than in the control group, not only after stimulus with D. pteronyssinus antigen, in vitro, but also with antigen from Candida albicans. This was not a serum effect. The late bronchial provocation response was lost only in those with serum IgA less than the log mean for age.

Adolescent↗

Is migraine food allergy? A double-blind controlled trial of oligoantigenic diet treatment.

93% of 88 children with severe frequent migraine recovered on oligoantigenic diets; the causative foods were identified by sequential reintroduction, and the role of the foods provoking migraine was established by a double-blind controlled trial in 40 of the children. Most patients responded to several foods. Many foods were involved, suggesting an allergic rather than an idiosyncratic (metabolic) pathogenesis. Associated symptoms which improved in addition to headache included abdominal pain, behaviour disorder, fits, asthma, and eczema. In most of the patients in whom migraine was provoked by non-specific factors, such as blows to the head, exercise, and flashing lights, this provocation no longer occurred while they were on the diet.

Abdomen↗

Immunological studies in asthmatic children undergoing antigen provocation in the skin, lung and nose.

In children with perennial asthma, dual (immediate and late) reactions in the skin to D. pteronyssinus and Timothy grass pollen were more frequent with high doses of antigen and were associated with large immediate reactions. The frequency of dual bronchial or nasal reactions was not related to the size of the immediate reaction and dual reactions were commonly elicited to the lowest antigen dose which would elicit an immediate reaction. Serum IgG, IgA, IgM or IgE concentrations, IgE or IgG antibodies to the antigens and defective yeast opsonization did not differ in children with dual or immediate only reactions in skin, nose or lung. In five patients undergoing bronchial provocation tests with D. pteronyssinus there was no fever, no fine crepitations in the lungs and no significant change in the levels of C3.

Adolescent↗