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K C Barnes

Publications and source records attributed to K C Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genetic markers of atopy in infancy: results from the German Multicenter Allergy Study.

Genetic studies of atopy-associated traits require unambiguous phenotypes to avoid both type 1 and 2 errors. The German Multicenter Allergy Study has provided a birth cohort with longitudinally well defined and stable phenotypes. We summarize data on candidate gene studies on chromosomes 12q, 5q, and 13q using high total IgE and atopic dermatitis (AD) as the most common atopy associated phenotypes in early childhood. We also present data on a functional RANTES promoter polymorphism that we recently identified. A significantly higher frequency of the mutant allele was seen in individuals of African descent compared to Caucasian subjects. In addition, an association of the polymorphism with AD could be demonstrated in the MAS cohort. Although the statistical approaches are limited, the MAS cohort has provided a valuable population for candidate gene studies in atopy.

Chemokine CCL5↗
PubMed1999

Gene-environment and gene-gene interaction studies in the molecular genetic analysis of asthma and atopy.

Asthma is a complex trait for which genetic predisposition is fundamental in disease aetiology, but poorly understood. Unravelling the genetic aetiology is complicated by the tremendous influence of the environment over disease expression. For this reason, asthma is multifactorial, in that disease expression is influenced by interactions between multiple major and minor genes, and modulated by interacting non-genetic factors (e.g. environment). 'Parent of origin' effects may be both genetic and environmental in aetiology, and have been observed in a number of population studies on asthma. The primary focus of this review is to evaluate the current approaches used in identifying the interrelationship between (1) certain environmental factors (e.g. allergen exposure, maternal inheritance) and genetic susceptibility to asthma and its associated phenotypes; and (2) candidate genes in chromosomal regions that have been linked to asthma and atopy in ongoing, molecular genetics studies.

Asthma↗
PubMed1998

Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: a genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: Dermatophagoides pteronyssinus (Der p) is one of the most frequently implicated allergens in atopic diseases. Although HLA could play an important role in the development of the IgE response to the Der p allergens, genetic regulation by non-HLA genes influences certain HLA-associated IgE responses to complex allergens. OBJECTIVE: To clarify genetic control for the expression of Der p-specific IgE responsiveness, we conducted a genome-wide search for genes influencing Der p-specific IgE antibody levels by using 45 Caucasian and 53 African American families ascertained as part of the Collaborative Study on the Genetics of Asthma (CSGA). METHODS: Specific IgE antibody levels to the Der p crude allergen and to the purified allergens Der p 1 and Der p 2 were measured. Multipoint, nonparametric linkage analysis of 370 polymorphic markers was performed with the GENEHUNTER program. RESULTS: The best evidence of genes controlling specific IgE response to Der p was obtained in 2 novel regions: chromosomes 2q21-q23 (P = .0033 for Caucasian subjects) and 8p23-p21 (P = .0011 for African American subjects). Three regions previously proposed as candidate regions for atopy, total IgE, or asthma also showed evidence for linkage to Der p-specific IgE responsiveness: 6p21 (P = .0064) and 13q32-q34 (P = 0.0064) in Caucasian subjects and 5q23-q33 (P = 0.0071) in African American subjects. CONCLUSIONS: No single locus generated overwhelming evidence for linkage in terms of established criteria and guidelines for a genome-wide screening, which supports previous assertions of a heterogeneous etiology for Der p-specific IgE responsiveness. Two novel regions, 2q21-q23 and 8p23-p21, that were identified in this study merit additional study.

Adult↗
PubMed1998

Linkage analysis of Dermatophagoides pteronyssinus-specific IgE responsiveness with polymorphic markers on chromosome 6p21 (HLA-D region) in Caucasian families by the transmission/disequilibrium test. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: Recently, we have obtained evidence for linkage between Der p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA). OBJECTIVE: Specific IgE antibodies toward different Dermatophagoides pteronyssinus (Der p) polypeptides were detected by immunoblotting analysis, and the transmission/disequilibrium test (TDT) was performed between specific IgE responsiveness toward each different Der p polypeptide and markers on chromosome 6p21 to better clarify the genetic contribution of HLA-D genes. METHODS: We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individuals that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT was conducted between the presence of specific IgE antibodies toward each of 12 different Der p polypeptides and 4 polymorphic markers on chromosome 6p21. RESULTS: The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed significant excess transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 55 kd, 45 kd, or 37 kd). In contrast, the 200-bp allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decreased transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in heterozygous parents was statistically significant after correcting for multiple comparisons. CONCLUSION: This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiveness in this Caucasian population. Our results, however, reveal the complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perhaps environmental factors for the development of Der p-specific IgE responsiveness.

Alleles↗
PubMed1998

Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: We have recently conducted a genome-wide screening for genes influencing Dermatophagoides pteronyssinus-specific IgE responsiveness as a part of the Collaborative Study on the Genetics of Asthma (CSGA), which showed evidence for linkage in some regions, including chromosomes 5131-q33 and 11q13 in African American families. OBJECTIVES: To clarify relative contributions of these regions to atopy in the same African American population, we have conducted further genetic linkage studies of specific IgE responses toward common inhaled allergens. METHODS: We studied 328 individuals in 58 African American families participating in the CSGA. Specific IgE responses toward Dermatophagoides farinae, cat, dog, American cockroach, rye grass, and Bermuda grass, as measured by skin tests, were used for multipoint linkage analysis with polymorphic markers on chromosomes 5q31-q33 and 11q13. RESULTS: Specific IgE response toward American cockroach showed evidence for linkage to chromosomes 5q31-q33 (P = .0050) and 11q13 (P = .017). Specific IgE response toward dog showed evidence for linkage with chromosome 5q31-q33 (P = .0043). Evidence for linkage with chromosome 11q13 was obtained for specific IgE responses toward Dermatophagoides farinae (P = .012), cat (P = .035), and Bermuda grass (P = .017). The presence of a positive ST response for at least 1 of 30 common allergens showed evidence for linkage to chromosomes 5q31-q33 (P = .017) and 11q13 (P = .00058). CONCLUSIONS: These data support that genes on both chromosomes 5q31-q33 and 11q13 confer susceptibility to upregulated IgE-mediated immune responses in this African American population. The putative genes on chromosomes 5q31-q33 and 11q13, however, showed contrasting effects on atopy, which may result from strong gene-environmental interactions.

Administration, Inhalation↗
PubMed1997

Evidence for linkage of chromosome 12q15-q24.1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study.

Linkage of asthma and high total serum IgE levels to chromosome 12q15-q24.1 has been recently described. To evaluate this region further in regard to total IgE responsiveness, we genotyped 52 unrelated German children with persistently "high" total serum IgE (selected from a noninterventional prospective multicenter cohort study) and their parents. We carefully defined a most extreme IgE phenotype and analyzed it as a dichotomous trait. We tested for linkage between high total IgE concentrations and nine polymorphic microsatellite markers on chromosome 12q15-q24.1 using the transmission/disequilibrium test. Evidence for linkage and allelic association for high total IgE was observed for four markers in this region. This study demonstrates the value of using extreme phenotypes in genetic analysis of a complex quantitative trait.

Child, Preschool↗
PubMed1997

Characterization of the allergens of the house dust mite Euroglyphus maynei.

BACKGROUND: The house dust mite Euroglyphus maynei inhabits homes in many parts of the world and is the source of many allergens. OBJECTIVE: The purpose of this study was to biochemically and immunologically characterize the major allergens of E. maynei. METHODS: Proteins in an extract of E. maynei were separated into 20 fractions by using preparative isoelectric focusing. Most proteins and allergens were contained in fractions 7 to 17 with pH of 4.8 to 8.0. The fractions were further characterized by nonreducing sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting with the serum of 16 individuals sensitive to E. maynei. RESULTS: Molecular weights and isoelectric points were assigned to 47 IgE-binding proteins in an E. maynei extract, and the frequency of IgE binding to each allergen was determined. Twenty-two of the allergens were recognized by more than 50% of the 16 sera, and all but one of the subjects had IgE that bound to more than 10 allergens (range, 0 to 32). One of the proteins was identified as the allergen Eur m 2. CONCLUSION: E. maynei is the source of at least 47 individual allergens that have been characterized by molecular weight, isoelectric point, and IgE-binding properties.

Allergens↗
PubMed1997

Spetial and temporal distribution of house dust mite (Astigmata:Pyroglyphidae) allergens Der p 1 and Der f 1 in Barbadian homes.

House features contribute to house dust mite abundance and, therefore, exposure to mite allergens. Our study assessed the hypothesis that modernization of the domestic environment in a tropical setting may lead to a level of allergen from the house dust mites Dermatophagoides pteronyssinus (Trouessart) and D. farinae Hughes that previously has been defined clinically as at risk for people who suffer from allergic disease. Allergen (Der p 1 and Der f 1) levels were measured at 4 sites (mattress, bedroom floor, living room floor, and furniture) in 17 houses in Barbados during dry and rainy seasons. Der p 1(17 of 17 homes) at all 4 sites did not vary significantly from the dry to rainy season. Allergen levels varied according to site, and were highest in living room furniture in both seasons (geometric mean 40.37 and 64.17 micrograms/g, respectively). Concentration of Der p 1 allergens were higher in concrete than in wood or mixed concrete and wood houses. Der f 1(9 of 17 homes) levels were lower than Der p 1 by 1/1,000 (both seasons). Results indicate that season is less important in regard to levels of Der p 1 than house construction and confirm other studies that implicate D. pteronyssinus as a more abundant source of allergen than D. farinae in this tropical setting.

Allergens↗
PubMed1996

Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations.

To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum IgE concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to this region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) controlling asthma and the associated "high total IgE" trait.

Adolescent↗
PubMed1996

Quality of housing and allergy to cockroaches in the Dominican Republic.

Fifty-one atopic asthmatic and/or allergic rhinitic children and 23 nonatopic control from Santo Domingo, the Dominican Republic, were skin tested with an extract mix of three cockroach species (Blattella germanica, Blatta orientalis, and Periplaneta americana). Sixteen percent of the atopics and none of the nonatopics demonstrated positive immediate skin reactions to the cockroach mix (chi 2 = 4.05, p = 0.04). Hypersensitivity was correlated with the quality of the homes; 22% (8/36) of the atopics who lived in a concrete home were skin test positive to the cockroach mix, while none (0/15) of the atopics who lived in a wood home were skin test positive (chi 2 = 4.86, p = 0.03). Although the incidence of cockroach allergy in this study is lower than that found elsewhere, these data support the notion that, in this tropical environment, sensitization to cockroaches is associated with housing quality.

Adolescent↗
PubMed1983

Differential distribution of distinct forms of myeloperoxidase in different azurophilic granule subpopulations from human neutrophils.

Myeloperoxidase (MPO), a characteristic enzyme of human polymorphonuclear neutrophils (PMN), is localized in specialized lysosomal or azurophilic granules, and can be resolved into three distinct forms (I, II, III) by ion-exchange chromatography. Granules were isolated from single donor PMN and fractionated with centrifugation into two different azurophilic subpopulations (high and low density) by banding in a continuous sucrose density gradient. Ion-exchange chromatography of granule extracts indicated that the lower density granules contained mainly MPO forms II and III while the higher density granules appeared to contain all three forms, but in much reduced amounts. Sodium dodecylsulfate polyacrylamide gel electrophoresis showed that, the mobilities of the heavy subunits of MPO appeared to be inversely related to the density of the granule population from which they were extracted. These observations suggest that the different forms of MPO may have distinct functional roles and/or are a possible reflection of maturational differences among the granule subpopulations.

Adult↗
PubMed1983

Density heterogeneity of neutrophilic polymorphonuclear leukocytes: gradient fractionation and relationship to chemotactic stimulation.

When elicited murine peritoneal exudate cells were subjected to Percoll density gradient centrifugation, polymorphonuclear neutrophils (PMN) were found to distribute over a broad spectrum of buoyant densities (1.10-1.06 g/ml). PMN isolated between approximately 1.10 and 1.085 g/ml were referred to as high density PMN (HD-PMN), and those isolated at approximately 1.085-1.06 g/ml were designated intermediate density PMN (ID-PMN). Cells were characterized on the basis of morphology and specific markers: PMN by lactoferrin immunocytofluorescence and macrophages by nicotinamide adenine dinucleotide glycohydrase activity. Macrophages banded near the top of the gradient with a peak at 1.04 g/ml. At increasing times following elicitation, the ratio of HD to ID-PMN decreased. Decreased density of either murine HD-PMN or human peripheral blood PMN could be induced in vitro by exposure of the cells to endotoxin-activated serum. A decrease in buoyant density of human PMN was also demonstrated in vitro using the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). The response was time dependent, related to dose, and appeared to be mediated by the cell membrane receptor for FMLP. A competitive antagonist of FMLP binding, carbobenzoxy-phenylalanyl-methionine, inhibited the density change with a calculated Kd similar to that reported for inhibition of FMLP-induced aggregation, degranulation, locomotion, and superoxide production. The FMLP-induced decrease in PMN density was shown to be directly correlated with increases in relative mean cell volume. The density response is a new measurement of PMN interaction with specific chemotactic factors, which may be important in the generation of PMN heterogeneity observed in elicited peritoneal exudate cells. In addition, this approach offers a means of physically separating "activated" from "resting" PMN and of studying resultant biochemical differences between these cell populations using both in vivo and in vitro systems.

Animals↗
PubMed1983

Phospholipid-sensitive Ca2+-dependent protein phosphorylation system in various types of leukemic cells from human patients and in human leukemic cell lines HL60 and K562, and its inhibition by alkyl-lysophospholipid.

Phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK), its endogenous substrate proteins, and regulation of the enzyme system by an antitumor agent alkyl-lysophospholipid were investigated in various types of leukemic cells (chronic myelocytic, acute myelocytic, and acute monocytic) from patients and in two cultured human leukemic cell lines (HL60 and K562). Exceedingly high levels of PL-Ca-PK, largely localized in the particulate fraction, were found in all types and lines of leukemic cells; much lower levels of cyclic adenosine 3':5'-monophosphate-dependent protein kinase and cyclic guanosine 3':5'-monophosphate-dependent protein kinase were also found. Although numerous and similar endogenous substrates for PL-Ca-PK were found in all cell types and lines examined, substrates specific for certain leukemic cells appeared to be present. Substrate proteins for calmodulin-sensitive Ca2+-dependent protein kinase, cyclic adenosine 3':5'-monophosphate-dependent protein kinase, and cyclic guanosine 3':5'-monophosphate-dependent protein kinase, in comparison, were much fewer or undetected. The PL-Ca-PK activity and the phosphatidylserine-Ca2+-stimulated phosphorylation of endogenous proteins from leukemic cells were inhibited by alkyl-lysophospholipid, which acted as a competitive inhibitor of the phospholipid cofactor of the enzyme. The findings suggested that the PL-Ca-PK system is a predominant protein phosphorylation system in leukemic cells and that this enzyme system may represent a site of cytotoxic action of alkyl-lysophospholipid.

Calcium↗
PubMed1981

Glucocorticoid-stimulated increase in chemotactic peptide receptors on differentiating human myeloid leukemia (HL-60) cells.

The effect of dexamethasone on the HL-60 human promyelocytic leukemia cell line was studied using a radioligand-binding assay for a chemotactic peptide receptor that is found on the surface of mature polymorphonuclear leukocytes. When dimethyl sulfoxide (DMSO) is added to cultures, HL-60 cells undergo morphological and functional differentiation over a period of 6 to 7 days. Differentiation is accompanied by increased binding of the synthetic N-formylated chemotactic peptide N-formylmethionylleucyl[3H]phenylalanine. Binding of N-formylmethionylleucyl[3H]phenylalanine to cells induced to differentiate with DMSO was temperature dependent, specific, saturable, of high affinity, reversible, and proportional to cell number. Dexamethasone increased the number of N-formylated chemotactic peptide receptors in cultures of differentiating HL-60 cells without affecting the affinity of the receptors for the tritiated peptide. This steroid response was dose dependent, proportional in magnitude to glucocorticoid activity, and abolished by cycloheximide. Dexamethasone had little effect on N-formylmethionylleucyl[3H]phenylalanine binding unless DMSO was also present in culture or the cells were first induced by DMSO to differentiate. These results suggest that the glucocorticoid stimulated increase in number of N-formylated chemotactic peptide receptors was mediated by the high-affinity glucocorticoid receptor, involved protein synthesis, and was apparently dependent on differentiation.

Cell Differentiation↗