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C Kelly

Publications and source records attributed to C Kelly.

At least 217 records · Page 12Linked to original sources

Surface and species-specific antigens of Schistosoma haematobium.

Of the surface antigens identified by radio-iodination, two-dimensional gel analyses showed no similarities between those of Schistosoma haematobium and Schistosoma mansoni, thus providing a basis for the species specificity of these antigens described previously (Simpson, Knight, Hagan, Hodgson, Wilkins & Smithers (1985) Parasitology 90, 499-508). The surface antigens of S. haematobium were glycosylated and comprised an acidic polypeptide of Mr 17,000 as well as a complex set of polypeptides of approximate pI 6-7, which resolved in the Mr range 20,000-30,000. At least one of the lower Mr forms of this complex is also present in the adult worm. Limited cross-reaction was observed with S. mansoni infection sera and this may be due to a shared carbohydrate epitope. In contrast, extensive cross-reaction was observed using sera from mice immunized with S. bovis. This pattern parallels the species-specificity of vaccine-induced immunity. Extensive cross-reaction was also observed within cell-free translation products of m-RNA from adult worms of S. haematobium and S. mansoni by use of heterologous human infection sera. The few antigens which were species-specific may represent surface antigens.

Animals↗

IgM antibodies recognizing carbohydrate epitopes shared between schistosomula and miracidia of Schistosoma mansoni that block in vitro killing.

A series of monoclonal antibodies (mAb) was raised in mice against Schistosoma mansoni, which recognized a carbohydrate determinant on a major Mr greater than 200,000 schistosomulum surface antigen. These mAb cross-reacted with the surface of cercariae and miracidia and with schistosomula of S. haematobium and S. bovis. Other mAb were generated that only recognized a Mr 20,000 schistosomulum surface antigen; they did not cross-react with eggs or miracidia and were species specific. The anti-Mr 20,000 mAb of the IgG1 isotype exhibited high levels of complement-dependent cytotoxicity to schistosomula in vitro. IgM mAb that recognized carbohydrate epitopes of the Mr greater than 200,000 surface antigen blocked the lethal activity of the anti-Mr 20,000 mAb. The IgM anti-Mr greater than 200,000 mAb also reduced complement-dependent cytotoxicity of serum from mice vaccinated with irradiated cercariae.

Animals↗

A major role for carbohydrate epitopes preferentially recognized by chronically infected mice in the determination of Schistosoma mansoni schistosomulum surface antigenicity.

A radioimmunoassay that makes use of whole schistosomula and 125I-labeled protein A has been used to characterize and to quantify the binding of antisera to the surface of 3 hr mechanically transformed schistosomula of Schistosoma mansoni. This technique facilitates the determination of epitopes on the schistosomula in addition to those detected by surface labeling and immunoprecipitation. By using this technique, it has been demonstrated that there is a much greater binding to the parasite surface of antibodies from chronically infected mice (CMS) than of antibodies from mice infected with highly irradiated cercariae (VMS), and CMS recognizes epitopes that VMS does not. Treatment of the surface of the schistosomula with trifluoromethanesulphonic acid and sodium metaperiodate has suggested that the discrepancy of the binding between the two sera is due to the recognition of a large number of additional epitopes by CMS, which are carbohydrate in nature. Some of the carbohydrate epitopes are expressed on the previously described surface glycoprotein antigens of Mr 200,000, 38,000, and 17,000.

Animals↗

The recognition of Schistosoma mansoni surface antigens by antibodies from patients infected with S. mansoni and S. haematobium.

Polypeptide surface antigens of Schistosoma mansoni recognized by schistosomiasis patients have been identified and their strain and species specificity investigated. Antibodies from individuals infected with S. mansoni were used in immunoprecipitation assays of 125I-labelled schistosomulum surface antigens. All individuals surveyed from St. Lucia strongly precipitated antigens of approximately Mr 38,000 to 32,000 and 20,000. These antigens were shown by two-dimensional gel electrophoresis to be the same as those recognized by experimentally immunized mice. Although individuals showed a highly heterogeneous response against total polypeptide antigens synthesized in vitro by cell-free translation of adult S. mansoni mRNA, all individuals recognized the same surface antigens. Immunoprecipitation with sera from patients infected with S. mansoni in many different parts of Africa resulted in generally the same antigens being precipitated, although a very high molecular weight antigen(s), not strongly recognized by the St. Lucian sera was also precipitated by most of the African patient sera. One serum from Ghana precipitated the high molecular weight antigen but not the low molecular weight antigens, raising the possibility of the existence of S. mansoni strain(s) exhibiting some diversity in surface antigens. The surface of S. mansoni schistosomula was found to bind strongly antibodies from individuals infected with S. haematobium, demonstrating that most surface antigens are cross-reactive. Immunoprecipitation demonstrated, however, that of the polypeptide surface antigens only the very high molecular weight antigen was recognized by anti-S. haematobium antibodies and that the 38,000 to 32,000 and 20,000 Mr antigens were species-specific. Immunoprecipitation of the polypeptide antigens derived from purified adult surface membranes demonstrated recognition of the same 32,000, 25,000 and 20,000 Mr antigens recognized by chronically infected mice. Again these antigens were found to be species-specific.

Adult↗

The effects of daily cyclophosphamide administration on the development and extent of primary experimental interstitial nephritis in rats.

We examined the effects of daily cyclophosphamide administration on the development and extent of tubulointerstitial nephritis produced in rats injected with tubular basement membranes in adjuvant. 15 mg/kg/day of cyclophosphamide completely blocked the development of interstitial lesions, while 2 mg/kg/day enhanced the degree of interstitial injury. When cyclophosphamide in the higher dose was started early in disease, 12 days after immunization, protection from progression was also observed as well as significant reductive improvement. If cyclophosphamide was administered late in disease, 21 days after immunization, no further progression was demonstrable, but substantial injury remained. In the latter two experiments, the beneficial effects of cyclophosphamide could not be explained by a reduction in anti-tubular basement membrane antibodies bound to the kidney. In groups of immunized rats that were tested, however, cyclophosphamide was able to non-specifically impair the delayed-type hypersensitivity response to tubular antigen and PPD. We conclude, therefore, that cyclophosphamide, in high but not low dosage, if given before damage is extensive and prolonged, may successfully inhibit the cellular immune response producing primary interstitial nephritis.

Animals↗

The effect of inspiratory resistive training on exercise capacity in optimally treated patients with severe chronic airflow limitation.

This study was designed to determine whether inspiratory resistive training could improve the exercise performance of patients with severe chronic airflow limitation who had already received optimum conventional therapy with bronchodilators and physiotherapy. Eighteen patients were studied. Ten patients were trained with an inspiratory resistance device for six weeks and eight patients used a placebo device. Psychological factors, likely to influence exercise capacity, were taken into account. Although there was no significant increase in maximum inspiratory pressure in the ten trained subjects, inspiratory muscle endurance was improved. Exercise performance, as assessed by progressive cycle exercise, stair climbing, 12 minute walking distance and treadmill walking did not change significantly in either group. It was concluded that inspiratory muscle training, using a currently available technique, produced no additional improvement in exercise capacity beyond that achieved by conventional bronchodilator and rehabilitation therapy.

Aged↗

Heart rate and respiratory patterns in mild hypoxia in unanaesthetized newborn mammals.

The heart rate and respiratory patterns in hypoxia are not well documented in unanaesthetized intact newborn animals. We studied heart rate and respiratory patterns during quiet sleep in 17% inspired O2 in 31 unanaesthetized newborns of five species: lamb, piglet, puppy, kitten, and rabbit. There was no significant change in mean heart rate and respiratory rate with hypoxia for any species. Brief apneas greater than 5 s were frequent (5-8/h), both in 21 and 17% O2 only in lambs and puppies. No sustained periodic breathing was induced by hypoxia. Thus, mild hypoxia has little steady-state effect on heart rate and respiratory rate and pattern in these unanaesthetized newborns. These findings are compatible with depressed chemoreceptor threshold, but indicate a remarkably mature respiratory pattern in full-term newborns of these species.

Animals↗

Characterization of the HLA-A2.2 subtype: T cell evidence for further heterogeneity.

Five blood donors were identified whose HLA-A2 is different from the common HLA-A2. Their A2 molecule (A2.2) had a more basic isoelectric point than normal A2 (A2.1). Cytotoxic T lymphocytes (CTL) restricted by HLA-A2.1, specific for influenza A and Epstein-Barr viruses, failed to lyse virus-infected target cells with HLA-A2.2. Identical patterns were obtained with both viruses. CTL from four of the A2.2-positive donors recognized target cells prepared from others in the group that shared only the HLA-A2.2 antigen. The A2.2 antigen from one donor seemed to be different in that target cells were not recognized by CTL from donors with the normal A2.1 nor with basic A2.2. There seems, therefore, to be heterogeneity within the HLA-A2.2 subtype.

Cytotoxicity, Immunologic↗

Schistosoma mansoni: complexity of antigenic and nonantigenic surface polypeptides.

Two-dimensional gel analysis of the surface polypeptides of the schistosomula stage of Schistosoma mansoni resolved a complex pattern of approximately 20 polypeptides. The majority of these were identified as immunogenic since they were immunoprecipitated with antisera from chronically infected mice and from mice vaccinated with irradiated cercariae. However, several major surface polypeptides were not immunoprecipitated by sera from infected or immune mice and were presumed to be nonantigenic.

Animals↗

Evidence that the 32, 38 and 20 kilodalton surface antigens of schistosomula and schistosomes are a family of conserved proteins.

The structures of the 38, 32 and 20 kDa surface antigens isolated from schistosomula and adult worms of Schistosoma mansoni were compared by two-dimensional peptide mapping, by immunological analysis and by one- and two-dimensional electrophoresis. Peptide mapping showed a high degree of similarity between the isolated antigens from both parasite stages. The NIMP/M47 monoclonal antibody showed cross-reactivity between the 32 and the 20 kDa antigens under denaturating and non-denaturating conditions, as demonstrated by immunoprecipitation and Western blotting. It is concluded that these antigens constitute a homologous family of surface antigens.

Animals↗