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Biomedical subjects

P C Potter

Publications and source records attributed to P C Potter.

At least 37 records · Page 2Linked to original sources

Year-round housedust mite levels on the Highveld.

OBJECTIVE: To determine the levels of the allergen DerPI, attributable to the house-dust mite (HDM) Dermatophagoides pteronyssinus. DESIGN: A four-season study conducted during 1994/95, sampling mattresses and carpets in the main bedrooms of suburban homes. SETTING: Thirty randomly selected homes in the Edenvale area, occupied by both black and white families living under similar socio-economic conditions in comparable environments. RESULTS: All homes tested positive for the allergen, and in 20% HDM levels exceeded levels recognised as 'safe' in terms of respiratory allergy, i.e. 2 micrograms/g of dust. Once mites were established in a home, they remained for months thereafter. The considerable seasonal variation recorded in HDM levels could not readily be explained. CONCLUSIONS: The HDM is extremely sensitive to minimal variations in microclimate. Its year-round presence is of concern on the Highveld. Infestation levels below 2 micrograms/g of dust, until recently considered the critical point for sensitisation, may be significant triggers of symptoms.

Black or African American↗

Characteristics of hypersensitivity reactions and identification of a unique 49 kd IgE-binding protein (Hal-m-1) in abalone (Haliotis midae).

BACKGROUND: There is a paucity of published data on the clinical presentation and the nature of the allergens involved in hypersensitivity to mollusks. This study reports the clinical and immunologic findings in 38 patients with reported immediate and delayed adverse reactions to abalone (Haliotis midae, Class Gastropoda). METHODS: Patients were recruited as part of a South African seafood allergy survey. Allergic symptoms were assessed by a self-administered questionnaire. A total of 38 patients with abalone sensitivity were recruited. Specific IgE responses to abalone and other mollusks were studied by using RAST and inhibition ELISAs. Skin prick tests and lymphocyte proliferation assays were also performed on several of the subjects. Allergenic components of Haliotis midae were identified with Western blotting. RESULTS: Twenty five of the 38 patients in the study were first seen with immediate symptoms, and 13 had delayed reactions. Seventeen of the sera tested were RAST positive. Skin prick tests responses with abalone extract were positive in all subjects with positive RAST responses (n = 8) and in 6 of 13 subjects with negative RAST responses. Five of the subjects with positive RAST responses had positive results on Western blotting and demonstrated binding to two major allergens with molecular weights of 38 and 49 kd. The 49 kd IgE-binding protein has been designated as Hal-m-1. CONCLUSIONS: Abalone allergens are heat-stable proteins with molecular weights of 38 and 49 kd, later designated as Hal-m-1 according to International Union of Immunological Societies allergen nomenclature regulation. Our studies indicate a clear clinical and immunologic heterogeneity in patients reactive to abalone.

Adolescent↗

Reduced interferon-gamma but normal IL-4 and IL-5 release by peripheral blood mononuclear cells from Xhosa children with atopic asthma.

BACKGROUND: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-gamma (IFN-gamma); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-gamma release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. OBJECTIVES: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-gamma release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. METHODS: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured. RESULTS: Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/IFN-gamma ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-alpha release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles. CONCLUSION: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-gamma release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-gamma release might be related to asthma severity.

Adolescent↗

The spectrum of allergy to South African bony fish (Teleosti). Evaluation by double-blind, placebo-controlled challenge.

OBJECTIVE: The aim of this study was to assess the spectrum of allergy to South African bony fish (Class Teleosti), crustaceans and molluscs and to confirm or refute suspected allergy, specifically to bony fish, by double-blind, placebo-controlled food challenge (DBPCFC). DESIGN: Patients were recruited by means of a seafood allergy questionnaire. Subjects with reported allergy to hake, yellowtail, salmon and mackerel were investigated by means of skin-prick tests, RASTs and Western blot analysis. For those subjects with test results that were either all negative or equivocal, a definitive diagnosis of clinical sensitivity was made on the basis of DBPCFC. SETTING: Volunteer population-based cohort in the Western Cape. PARTICIPANTS: 105 volunteer subjects with suspected fish allergy were recruited by advertising in the local press. MAIN OUTCOME: Species-specific bony fish allergy was confirmed or refuted by DBPCFC. RESULTS: The four most common seafood species reported to cause adverse reactions were prawns (46.7%), crayfish (43.8%), abalone (35.2%) and black mussels (33.3%). The four most common bony fish species to cause reactions were hake (24.8%), yellowtail (21.9%), salmon (15.2%) and mackerel (15.2%). Seven DBPCFCs were performed and two open challenges. Skin-prick tests produced one false-negative result. Western blots produced one false-negative and one false-positive result. The RAST had a 100% correlation with DBPCFC. CONCLUSIONS: Local bony fish represent a significant cause of clinical reactions to seafood in the Western Cape. Although skin-prick tests, RASTs and Western blotting tests assist in the documentation of an IgE responder state, confirmation of clinical sensitivity can only be made with certainty by means of DBPCFC.

Adolescent↗

In vivo and vitro in diagnosis of latex allergy at Groote Schuur Hospital.

OBJECTIVE: The aim of this study was to evaluate the diagnostic utility of skin-prick tests, radio-allergosorbent tests (CAP RASTs), basophil histamine release, sulphidoleukotriene release and Western blotting in the diagnosis of latex allergy at Groote Schuur Hospital. DESIGN: Patients with a history suggesting latex hypersensitivity were recruited via staff health and allergy clinics at Groote Schuur Hospital. A clinical assessment was followed by laboratory investigation and skin-prick testing. A control group consisted of laboratory and hospital staff who had regular latex exposure but were asymptomatic. SETTING: Hospital-based cohort at Groote Schuur Hospital. PARTICIPANTS: Twenty-three patients with suspected latex allergy; 10 control subjects exposed to, but not clinically sensitive to, latex. MAIN OUTCOME: Skin-prick testing was more sensitive than in vitro diagnostic tests for the diagnosis of latex allergy. RESULTS: Eighteen of 21 (85.7%) of the patients tested had a positive skin-prick test with a commercial latex solution (Allerbioprick) and 17/21 (80%) tested skin-prick-positive with an in-house glove extract. CAP RASTs were positive in 13/23 patients (56.5%), sulphidoleukotriene release was positive in 10/23 (43%), histamine release assay was positive in 10/23 (45%) and Western blots were positive in 8/23 (34.7%). All patients with only urticaria were Western blot-negative and CAP RAST-negative, suggesting that they have very little circulating latex-specific IgE. Although patients who were Western blot-positive tended to have multi-organ involvement, both patients with anaphylaxis were Western blot-negative. CONCLUSION: Latex allergy is a significant clinical problem at Groote Schuur Hospital. Titrated skin-prick testing performed in a controlled environment can safely and reliably confirm the diagnosis in patients who do not give a history of anaphylaxis. The CAP RAST was the most sensitive in vitro test for latex allergy locally available, but lacks sensitivity in patients presenting with urticaria only.

Adult↗

Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies.

Combined subtotal deficiency of C6 and C7, in which both proteins are expressed at very low levels, has been observed in homozygous form in two families. A defect at the 5' splice donor site of intron 15 of the C6 gene explains the low molecular weight of the C6 protein and is probably responsible for its low expressed concentration. The C7 defect is more enigmatic: the protein is of normal molecular weight, low circulating concentration, and altered isoelectric point. An Arg > Ser codon substitution in exon 11 is the only molecular alteration within the mature C7 protein. These defects are associated with a characteristic set of polymorphic DNA markers in the C6/C7 region, forming a distinct haplotype. The haplotype has been found in combination with a number of other haplotypes containing defective genes that lead either to C6 or C7 deficiency, but with different consequences. Where it is combined with a C6-deficient gene, the serum C7 levels can be surprisingly high, possibly because there is no C6 generating C56 to consume the C7. In contrast, where the C7 genes are both defective (but still partially functional), there may be a profound deficit of circulating C7 because there is ample C6 to produce C56 and consume the already small amount of C7. Each molecular defect has also been found in isolation and has the expected effect.

Amino Acid Sequence↗

Granulocyte proteins in serum in childhood asthma: relation to spirometry and therapy.

BACKGROUND: Measurement of markers of eosinophil activation in asthmatics provides information indicative of ongoing inflammatory processes in the airways. OBJECTIVES: This study was conducted to determine the correlations between serum markers of allergic inflammation with spirometry parameters in asthmatic children in different treatment groups. METHODS: Blood eosinophils, serum levels of eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and tryptase were measured simultaneously with serial measurements of FEV1/FVC, FEF25-75 and FEF in 60 children with acute asthma on admission and after 2, 14, 30 and 60 days. Group A received bronchodilators only (n = 20), group B received sodium cromoglycate (SCG) (n = 20) and group C received oral and/or inhaled corticosteroids (n = 20). RESULTS: Oral steroid treatment (2 mg/kg/day), given at the onset of the asthma attack, resulted in significant reduction in the ECP and EPX levels in all the children. However, these reduced ECP and EPX levels were not sustained in the children, even in those who continued on maintenance steroid treatment. Significant, but inconsistent, correlations between ECP, EPX with total eosinophil count, Percentage eosinophils and spirometry parameters were observed at the different time-points. Tryptase levels were normal in all subjects. There were no significant correlations between myeloperoxidase levels and the spirometry parameters or eosinophil parameters. Serial monitoring of ECP and EPX levels was found to be of some use in predicting clinical outcome in certain steroid-dependent asthmatics (group C) but of no value in the mild asthmatics (group A). CONCLUSION: While elevation of ECP, EPX and MPO in the serum of childhood asthmatics suggests ongoing inflammation and may inversely correlate with spirometry parameters in some patients, the relationship between these markers and airway function is not a simple one.

Adolescent↗

Complement component C6 and C7 haplotypes associated with deficiencies of C6.

Both complete C6-deficiency (C6*Q0) and subtotal C6-deficiency (C6*SD) have been described as simple recessive traits and C6*SD has been described in combination with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6 protein found in both C6*SD traits is phenotypically indistinguishable, being smaller than normal C6 and having different isoelectric properties. A defect has been found in the C6 gene which plausibly explains the C6*SD phenotype, and this defect is also common to both C6*SD traits. We present data from seven DNA markers of the C6 and C7 genes which show that although at least four haplotypes are associated with C6*Q0, most South African C6*Q0 patients carry a common defective haplotype. The most common haplotype associated with C6*Q0 has been observed only once among unaffected haplotypes of relatives. In one family, the cases of C6*SD share a complete haplotype with both cases of combined deficiency and are probably heterozygous for this condition and complete deficiency of C6. In another family, the C6*SD is on a slightly different haplotype and C7 is normally expressed. Thus, the C6 defect is not sufficient on its own to explain the C7 deficiency in the combined deficient haplotype. The haplotype associated with the combined deficiency is found not only in normal control subjects, but also in one case of complete C6 deficiency. In this case the molecular defect seen in combined or C6*SD cases is absent.

Alleles↗

Immediate and delayed contact hypersensitivity to verbena plants.

Plants from the Verbenaceae family may cause contact dermatitis of unknown nature. This report describes 2 cases of allergic reactions to the Verbena species. A teenage boy developed an anaphylactic allergic response following contact with the leaves of Verbena hybrida. Characterization of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida, a common perennial in South African gardens. The other case was a 23-year-old female gardener who developed immediate and delayed-type contact dermatitis from Verbena elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material were considered positive and of an allergic nature.

Adolescent↗

Molecular basis of subtotal complement C6 deficiency. A carboxy-terminally truncated but functionally active C6.

Individuals with subtotal complement C6 deficiency possess a C6 molecule that is 14% shorter than normal C6 and present in low but detectable concentrations (1-2% of the normal mean). We now show that this dysmorphic C6 is bactericidally active and lacks an epitope that was mapped to the most carboxy-terminal part of C6 using C6 cDNA fragments expressed as fusion proteins in the pUEX expression system. We thus predicted that the abnormal C6 molecule might be carboxy-terminally truncated and sought a mutation in an area approximately 14% from the carboxy-terminal end of the coding sequence. By sequencing PCR-amplified products from this region, we found, in three individuals from two families, a mutation that might plausibly be responsible for the defect. All three have an abnormal 5' splice donor site of intron 15, which would probably prevent splicing. An in-frame stop codon is found 17 codons downstream from the intron boundary, which would lead to a truncated polypeptide 13.5% smaller than normal C6. This result was unexpected, as earlier studies mapped the C5b binding site, or a putative enzymatic region, to this part of C6. Interestingly, all three subjects were probably heterozygous for both subtotal C6 and complete C6 deficiency.

Amino Acid Sequence↗

Accumulation of house-dust mite (Der-p-1) levels on mattress covers.

Mattresses serve as a large reservoir for house-dust mite antigens and harbour the highest mite levels within the household. Mite reduction measures have previously been shown to be unsuccessful. The effect of mattress covers and acaracides on Der-p-1 levels in the mattresses of 60 patients with mite-allergic asthma was studied. Der-p-1 levels were measured using monoclonal antibodies (ELISA method). Baseline levels were recorded and re-assessed at 8-week intervals over a 6-month period. Patients were randomised into three equal groups. In group A mattresses were treated with Metsan (Snowchem) and benzylbenzoate only; group C had their mattresses covered with mattress covers (Allergy Control Products). Group B was the control group. We were unable to demonstrate any reduction of mite levels in the beds of all 3 groups. In fact all 3 groups demonstrated an increase in Der-p-1 levels over the study period, viz. group A (mean pre: 14.28, post: 34.18 micrograms/g dust); group C (mean pre: 8.26, post: 20.80 micrograms/g dust) and group B (mean pre: 18.21, post 38.47 micrograms/g dust). However, 12 patients in group C had their mattress covers washed in hot water at weekly intervals over a 5-week period at the end of the study. The results demonstrated a significant reduction in mite levels (mean pre: 41.95, post: 26.2 micrograms/g dust; P = 0.027). We therefore conclude that the use of mattress covers per se does not reduce Der-p-1 levels. The regular application of benzylbenzoate and Metsan does not prevent the accumulation of Der-p-1 on mattresses either.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

C6 haplotypes: associations of a Dde I site polymorphism to complement deficiency genes and the Msp I restriction fragment length polymorphism (RFLP)

Complement C6 has a common charge polymorphism designated A and B with gene frequencies of 0.65 and 0.35. The probable molecular basis for this is a Glu (C6A) for Ala (C6B) substitution at amino acid position 98, and is detected by digestion with the restriction enzyme Dde I of a polymerase chain reaction (PCR)-amplified fragment of genomic DNA. C6A was found to be Dde I-positive and C6B corresponds to Dde I-negative. We have applied our Dde I A/B polymorphism genotyping method to the investigation of C6-deficient individuals with complete (C6Q0) and sub-total deficiency (C6SD) protein phenotypes, including members of four families. We have also investigated the RFLP detected by digestion of genomic DNA with the enzyme Msp I, which is due to a polymorphic site located in the 5' section of the gene, the variable sequence of which has yet to be determined. Sixteen out of seventeen unrelated C6Q0 subjects were found to be genotypically Dde I B/Msp I-negative; the remaining subject was heterozygous at both the loci under investigation. The C6SD phenotype was found to be associated with the Dde I A/Msp I-positive genotype in two families with combined C6/C7 subtotal deficiency and two with C6SD. It can be concluded that the two forms of C6 deficiency, C6Q0 and C6SD, arose independently on two different C6 allelic backgrounds. These associations have allowed the genotyping of the rare families that contain both types of deficiency. We have also defined a number of normal C6 Dde I/Msp I haplotypes in Caucasians and Cape Coloured populations.

Adult↗

The effects of a single treatment of an acaricide, Acarosan, and a detergent, Metsan, on Der p 1 allergen levels in the carpets and mattresses of asthmatic children.

Baseline levels of the house-dust mite allergen, Der p 1, were measured on the carpets and mattresses of 60 pure-mite-sensitive asthmatic children in the Cape Peninsula, by means of an enzyme-linked immunosorbent assay (ELISA). High levels of mite allergens were recorded (range 2-50 micrograms Der p 1/g dust). In order to investigate the efficacy of the application of acaricides to carpets and bedding, 3 groups of 20 children were studied. Carpets and mattresses in group A were treated with a detergent, Metsan (Snowchem), and in group B with Metsan combined with the acaricide, Acarosan (Noristan). Group C was a control group in which no treatment was applied. The level of airway hyperreactivity (PC20) to histamine was measured at the beginning of the study and again 3 months after acaricide treatment. Significant reductions in carpet Der p 1 levels were achieved in group A (22.83 v. 13.26 micrograms Der p 1/g dust; P = 0.04) and group B (21.76 v. 13.26 micrograms Der p 1/g dust; P = 0.01), but mite levels were not reduced in any of the mattresses treated. There was also no improvement in airway hyperreactivity in any of the groups. This study clearly demonstrates that at present it is not possible to reduce Der p 1 antigen levels in mattresses in the Cape Peninsula with the available acaricides, even when one of these is combined with a detergent solution. Until strategies are developed which will significantly reduce Der p 1 levels in the bedding of sensitive individuals, a reduction in ongoing airway inflammation and airway hyperreactivity cannot be expected.

Animals↗