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Biomedical subjects

A J Chapman

Publications and source records attributed to A J Chapman.

At least 37 records · Page 2Linked to original sources

Glycosylation of human thyroglobulin and characterization by lectin affinity electrophoresis.

Thyroglobulin, a 660 kDa glycoprotein, is the major product of protein synthesis in the thyroid gland. It has been suggested that modifications of thyroglobulin glycosylation occur in various thyroid disorders. In order to study possible changes in glycosylation of tissue thyroglobulin associated with thyroid disease, we have developed a lectin affinity electrophoresis system which allows characterization of small (less than 1 microgram) quantities of thyroglobulin. Human thyroglobulin was extracted and purified. Agarose gels were cast containing concanavalin A, Ricinus communis agglutinin, L-phytohaemagglutinin and pokeweed mitogen at various concentrations. Purified human thyroglobulin was serially diluted, loaded onto lectin gels and electrophoresed. Concanavalin A, R. communis agglutinin and phytohaemagglutinin all bound thyroglobulin in a concentration-dependent manner. Pokeweed mitogen did not bind thyroglobulin. Purified thyroglobulin was treated with neuraminidase and endoglycosidase H. Two-dimensional immunoelectrophoresis revealed the migration of thyroglobulin to be modified by neuraminidase but not by endoglycosidase H. Lectin affinity electrophoresis of purified human thyroglobulin with and without enzyme treatment indicated the presence of: oligomannose structures as shown by concanavalin A reactivity and modification by endoglycosidase H, and complex oligosaccharides as shown by affinity for R. communis agglutinin and modification by neuraminidase. These structures are in keeping with the proposed patterns of glycosylation of human thyroglobulin and indicate suitability of the method for characterizing the glycosylation of small quantities of thyroglobulin.

Acetylglucosaminidase↗

Natural and vaccine-related immunity to Streptococcus pneumoniae.

To investigate the protective effects of pneumococcal vaccine, we assayed serum from healthy adults and from elderly bronchitics for antibody and opsonic activity against nine serotypes of S. pneumoniae. Before vaccination, there was no relation between opsonization and the level of antibody measured by RIA. Some serotypes were well opsonized in the absence of detectable antibody to capsular polysaccharide; others were not, despite modest levels of antibody. These in vitro studies did not support the concept that a certain level of antibody (e.g., greater than or equal to 250 ng of antibody nitrogen/ml) was specifically associated with the capacity to opsonize pneumococci. Nearly all postvaccination sera had increased antibody and opsonic activity against all serotypes, but the lack of correlation in any individual serum persisted. RIA showed that pre- and postvaccination levels of antibody in elderly adults with chronic lung disease were similar to those of younger adults. In elderly bronchitics, opsonizing activity for six of the nine serotypes was lower after vaccination, a result of suggesting a possible explanation for the failure of pneumococcal vaccine to be fully protective in these subjects. Elderly subjects had higher levels of antibody to phosphocholine, but when isolated, this antibody did not opsonize any of the vaccine strains of pneumococci. These results suggest that alternative strategies are needed to maximize the protective effect of pneumococcal vaccine in the population at greatest risk.

Adult↗

Peripheral vision and the aetiology of child pedestrian accidents.

Three experiments examined whether age and sex differences in pedestrian accidents might be partly attributable to differences in the visual perception of peripheral stimuli. Primary schoolchildren and adults responded individually to the presentation of lights at retinal eccentricities of 2 degrees, 20 degrees and 40 degrees. Experiments 1 and 2 measured reaction times and Expt 3 measured subjects' expectations of foveal and peripheral events. There were no age or sex differences in expectations. Lights were detected fastest in the 20-40 degrees range. Movement times were not variable across eccentricities. As expected, adults' and 11-year-olds' detections were faster than eight- and six-year-olds'. A case is made for more problem-analytic and multi-theoretical research in the area of the child pedestrian accidents.

Accidents, Traffic↗

Peripheral vision and child pedestrian accidents.

In both adults and children, peripheral vision is poorer than foveal vision, but there is evidence that detection in peripheral vision is relatively poorer in children than it is in adults. That may contribute to the particularly high pedestrian accident rates of children. Two laboratory experiments investigated peripheral vision in men and women and in boys and girls aged 7, 9 and 11. Using an array of stationary lights, Expt 1 examined reactions to apparent movement (the phi phenomenon) in mid and extreme periphery; and, using film sequences of a moving car, Expt 2 included a comparison of foveal and peripheral fields. Overall there was little evidence to support the hypothesis that children have poorer peripheral vision than adults relative to their foveal vision. Nonetheless there were some experimental differences: in Expt 1, 7-year-olds made fewer detections, particularly in the extreme periphery; and, in both experiments, detections tended to be slower. The relatively complex car movements in Expt 2 were detected faster in foveal than peripheral vision. There were no sex differences. Children detected more movements on the left. In Expt 2 these detections were faster, and children made relatively more simulated road crossings when the car approached from the left (all adults 'crossed' in all trials).

Accidents, Traffic↗

Emergence of bactericidal and opsonizing antibody to Vibrio vulnificus following bacterial infection.

Virulent isolates of Vibrio vulnificus resist the bactericidal and opsonizing effects of normal human serum, in contrast to environmental isolates, which are highly serum susceptible. Immune responses to bacteremic V. vulnificus infections in human subjects have not been characterized. Serum from a patient who survived sepsis caused by V. vulnificus had substantial bactericidal and opsonizing immunoglobulin G (IgG) for his own bloodstream isolate. Killing was mediated by the classical complement pathway, whereas opsonization was effected by either the classical or the alternative pathway. IgG that reacted strongly with 55-, 58-, and 68-kilodalton outer membrane proteins was present in the patient's convalescent-phase serum but was absent from normal human serum. These findings suggest that humoral immunity to V. vulnificus, mediated by bactericidal and opsonizing antibody, emerges during infection and may be due, in part, to IgG directed against identifiable outer membrane proteins.

Antibodies, Bacterial↗

Delayed puberty.

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Adolescent↗

Development of bactericidal antibody during Branhamella catarrhalis infection.

The recent observation that Branhamella catarrhalis may cause a variety of infections in humans has stimulated interest in human host defenses against this organism. We encountered 21 patients with B. catarrhalis infection: seven with pneumonia, 13 with a purulent exacerbation of chronic bronchitis, and one with purulent sinusitis. Normal human serum (NHS) demonstrated no bactericidal activity against 20 of the 21 isolates. In contrast, 7 of 19 acute and 18 of 20 convalescent sera demonstrated significant bactericidal effects against the corresponding B. catarrhalis isolate. Heating convalescent sera to 56 C for 30 min abolished bactericidal activity. This activity was restored by NHS but not by complement-rich guinea pig serum. Selective blockage of the classic complement pathway eliminated bactericidal activity, whereas selective blockage of the alternative pathway did not. IgG isolated from convalescent serum plus NHS was bactericidal for the corresponding B. catarrhalis isolate. These results suggest that most patients with pulmonary infections due to B. catarrhalis develop a convalescent IgG antibody response that mediates serum bactericidal activity by the classic complement pathway.

Acute Disease↗

Gonococcal endocarditis: a case series demonstrating modern presentation of an old disease.

Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today. We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade. Three episodes involved the aortic valve and required emergency aortic valve replacement. One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone. Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported. These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management.

Adult↗

Left atrial myxoma. A case report of unusual complication.

Atrial myxoma may present in unusual fashion and must be considered in the differential diagnosis of several conditions. A 17-year-old, white male presented with central nervous system symptoms, and the diagnosis was established postmortem. A brief discussion of tumor characteristics and diagnostic methods is made.

Adolescent↗

Discordant serum alpha-subunit and FSH concentrations in a woman with a pituitary tumour.

We have studied a women who presented at the age of 51 with a large FSH and alpha-subunit producing pituitary adenoma. Following insertion of ventriculo-peritoneal shunts and external pituitary irradiation there was no change in the elevated serum concentrations of FSH, and alpha-subunit over a four year period although she developed both ACTH and TSH deficiency. Various drugs, however, did alter the FSH and alpha-subunit concentrations and these changes suggest possible mechanisms controlling FSH secretion. Ethinyloestradiol 0.03 mg daily for three weeks suppressed serum FSH to 77% of the basal level (240 +/- 35 i.u./l to 184 +/- 20 i.u./l) but alpha-subunit rose to 130% of basal level (281 +/- 50 ng/ml to 366 +/- 40 ng/ml). On ethinyloestradiol 0.1 mg daily, FSH suppressed to 17% of basal (40 +/- 11 i.u./l) with no change in alpha-subunit concentration, while on 0.2 mg daily suppression of FSH was similar but alpha-subunit fell to 59% of basal (190 +/- 28 ng/ml). Dexamethasone, 3 mg daily for one week reduced FSH to 53% of the initial concentration and alpha-subunit to 74% while bromocriptine 7.5 mg daily for three months, reduced FSH to 39% and alpha-subunit to 66% of basal. Neither thyroxine, 0.2 mg daily for four weeks, nor an LHRH analogue, (Buserelin, Hoechst) 200 micrograms, three times daily for three months elicited any effect. Chromatography on Sephadex G100 showed that serum FSH and alpha-subunit both had Kav values somewhat lower than those of their standard counterparts (FSH, 0.20 vs 0.25; alpha-subunit 0.35 vs 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Chromophobe↗

Lack of binding of serum glycoprotein hormone alpha subunit to concanavalin A-Sepharose reflects increased branching of the oligosaccharide chains.

The lectin-binding properties of serum alpha subunit were studied by lectin affinity chromatography. Normal individuals and most patients with pituitary tumours produced alpha subunit which bound specifically to Concanavalin A-Sepharose (Con A). Some patients with pituitary tumours produced both Con A-reactive alpha subunit and alpha subunit which did not bind to Con A. Concanavalin A-Sepharose-binding alpha subunit from all sources bound strongly to Ricinus communis agglutinin-Sepharose after treatment with neuraminidase. Serum alpha subunit from those patients with pituitary tumours, which did not bind to Con A, bound to wheat germ agglutinin-Sepharose, exhibiting both weakly binding and strongly binding forms. Serum alpha subunit from both patients and controls, which did bind to Con A, showed only weak affinity for wheat germ agglutinin-Sepharose. Neither the low affinity nor the high affinity of serum alpha subunit from any source for wheat germ agglutinin-Sepharose was affected by neuraminidase. These findings show that (a) the predominant pattern of glycosylation of serum alpha subunit from normal controls is a Con A-reactive, biantennate complex oligosaccharide and (b) that the structural alteration which results in serum alpha subunit which does not bind to Con A in some patients with pituitary tumours is not an absence of carbohydrate, rather the alpha subunit contains highly branched, either complex or hybrid oligosaccharides.

Adult↗

Variation in the core and branch carbohydrate sequences of serum glycoprotein hormone alpha subunit as determined by lectin affinity chromatography.

Serum alpha subunits from patients with pituitary tumours and from normal controls were studied for their ability to bind to Lens culinaris agglutinin-Sepharose (LCA), L-phytohaemagglutinin-agarose (L-PHA) and soybean agglutinin-Sepharose (SBA). Serum alpha subunits from normal controls which had previously been shown to bind to Concanavalin A-Sepharose (Con A) were not retained by LCA. In contrast, Con A-reactive alpha subunits from patients with pituitary tumours bound specifically to LCA. Non-Con A-reactive alpha subunits from patients with pituitary tumours were also largely not bound to LCA, but were retained by L-PHA. No alpha subunits from any source bound to SBA. These results indicate that the structural alterations resulting in non-Con A-reactive serum alpha subunits include highly branched complex oligosaccharides in addition to the hybrid-type glycans previously described. The increased branching appears to be associated with fucosylation in the core region of the oligosaccharides. Serum alpha subunit from any source appears to be devoid of terminal N-acetylgalactosamine residues. These structural modifications may be related to the variable biological activity of alpha subunit which has been reported.

Carbohydrate Sequence↗

Wandering missiles: autopsy study.

Five cases of firearm missile emboli are reported. Three were not unusual arterial bullet emboli. One, however, was a single shotgun pellet embolus which produced death from cerebral infarction. The fifth case appears to be the first known to embolize within the portal system and was associated with a 'wandering bullet' within the pericardial space.

Adolescent↗

Pregnancies in women with hyperprolactinaemia: obstetric and endocrinological management of 50 pregnancies in 37 women.

Fifty pregnancies occurred in 37 women with hyperprolactinaemia. Thirty women (81%) initially attended with infertility and 24 (65%) had secondary amenorrhoea. Twelve women (31%) had pituitary macroadenomas, of whom seven (19%) were treated with neurosurgery and/or external radiotherapy before conception. Forty-one conceptions (82%) followed treatment with bromocriptine. There were no unusual obstetric or endocrinological complications. Serum prolactin measured at least 6 months post partum when under basal conditions, without bromocriptine and not breast feeding, showed no significant trends compared with initial values. Tumour growth was not stimulated by the high oestrogen levels of pregnancy.

Adolescent↗