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Biomedical subjects

E J Ball

Publications and source records attributed to E J Ball.

At least 19 recordsLinked to original sources
PubMed2001

HLA-B27 polymorphism.

HLA-B27 is a serologic specificity that encompasses 25 different alleles that encode 23 different products (proteins): HLA-B*2701 to B*2723. These alleles are also called subtypes of HLA-B27, and they may have evolved from the most widespread subtype, B*2705. These subtypes are distinguished from changes mostly in exons 2 and 3, which encode the alpha 1 and alpha 2 domains of the B27 molecule, respectively. Occurrence of ankylosing spondylitis (AS) or related spondyloarthropathy (SpA) has thus far been documented in subjects possessing any one of the first ten (B*2701 to B*2710) subtypes studied. However, B*2706 in Southeast Asian and B*2709 in the Italian island population of Sardinia seem not to be associated with AS. The 13 most recent subtypes have not yet been studied for disease association. It is important to investigate which of them are and are not associated with AS and related SpA, and whether certain subtypes show any preferential association with some of the clinical features or forms of these diseases among the various ethnic/racial populations and geographic regions of the world. This is expected to provide clues as to the mechanism of disease association, and one of the strongest reasons to study the B27 subtypes is to learn the effects of the sequence variations on the peptide-binding specificity of the molecule. Among these peptides may be the putative arthritogenic peptide(s).

Alleles↗
PubMed2001

Resolution of cis-trans ambiguities between HLA-DRB1 alleles using single-strand conformation polymorphisms and sequencing.

DNA-based typing of HLA alleles occasionally results in the inability to assign a specific allele because of ambiguity in associating two or more polymorphisms to the same or to alternate homologs (cis/trans ambiguity). Since most individuals are heterozygous at a given HLA locus, the highest level of confidence in definition is obtained when the alleles are tested in isolation. By using single-strand conformation polymorphisms (SSCP) to separate heterozygous HLA-DRB1 alleles, followed by sequencing of separated conformers, we have achieved resolution of previously ambiguous assignments without the need for additional probes or primers.

Alleles↗
PubMed2001

Total energy expenditure, body fatness, and physical activity in children aged 6-9 y.

BACKGROUND: The recent worldwide increase in the prevalence of childhood obesity may be due in part to a decrease in children's physical activity levels. OBJECTIVE: The current study of children in the years just before puberty aimed to 1) measure total energy expenditure (TEE) by use of the doubly labeled water (DLW) method, 2) determine the proportion of TEE related to physical activity, 3) investigate the relations between measures of physical activity and body fatness, and 4) investigate possible sex differences in these relations. DESIGN: The DLW technique was used to measure TEE over 10 d in 106 healthy children (52 boys) aged 7.8 +/- 0.9 y (x +/- SD). Fat-free mass, and hence fat mass, was derived from the (18)O dilution space. Resting energy expenditure (REE) was calculated with use of the Schofield equations. Physical activity level was calculated as TEE/REE. RESULTS: Mean TEE in both boys (7871 +/- 1135 kJ/d) and girls (7512 +/- 1195 kJ/d) was significantly different (P < 0.0001) from FAO/WHO/UNU recommendations (13% and 9% lower, respectively). There was no significant difference in physical activity level between boys (1.69 +/- 0.22) and girls (1.71 +/- 0.23). In boys but not girls, physical activity level was inversely correlated with BMI (r = -0.37, P < 0.01), fat mass (r = -0.46, P < 0.005), and percentage of body fat (r = -0.50, P < 0.0001). CONCLUSIONS: In boys but not girls, percentage of body fat is inversely associated with physical activity level. Physical activity is one factor contributing to body fatness in boys, but additional factors may influence the size of the fat stores in girls.

Adipose Tissue↗
PubMed2001

Comparison of total energy expenditure and energy intake in children aged 6-9 y.

BACKGROUND: The accurate measurement of food intake in children is important for assessing nutritional status. OBJECTIVE: We sought to both compare measurements of energy intake (EI) from diet records and of total energy expenditure (TEE) by the doubly labeled water (DLW) method and to investigate misreporting of EI. DESIGN: Forty-seven children (22 boys and 25 girls) aged 7.4 +/- 0.8 y ( +/- SD) were recruited from 25 schools in western Sydney. TEE was measured by DLW over 10 d and EI by use of 3-d food records. Misreporting was defined as [(EI - TEE)/TEE] x 100%. RESULTS: Girls had a higher (P = 0.02) percentage of body fat (28.2 +/- 7.0%) than did boys (22.9 +/- 8.0%); otherwise there were no differences among sex. Although mean (+/-SD) values for EI (7514 +/- 1260 kJ/d) and TEE (7396 +/- 1281 kJ/d) were not significantly different, there was no significant correlation between EI and TEE. EI and TEE were 9% and 11% lower, respectively, than current World Health Organization recommendations for EI. The relative bias (mean difference, EI - TEE) was low at 118 kJ/d, but the limits of agreement (bias +/- 2 SD of the difference) were wide at 118 +/- 3345 kJ/d. Although the mean percentage of misreporting was low (4 +/- 23%), the high SD indicates large intraindividual differences between EI and TEE. The most significant predictor of misreporting was dietary fat intake (r(2) = 0.45, P < 0.0001). Misreporting was not associated with sex or body composition. CONCLUSIONS: In this age group, reported EI is not representative of TEE at the individual level. However, at the population level, 3-d food records may be used for surveys of EI by 6-9-y-old children.

Anthropometry↗
PubMed2001

HLA-B27 and genetic predisposing factors in spondyloarthropathies.

With the mapping of the human genome having been completed, our ability to investigate and ideally better understand the genetic basis of rheumatic diseases is advancing at a rapid pace. Substantial evidence strongly favors a direct role for HLA-B27 in genetic susceptibility to ankylosing spondylitis and related spondyloarthropathies, although the underlying molecular basis has yet to be identified. HLA-B27 contributes only 16 to 50% of the total genetic risk for the disease, clearly indicating that other genes must be involved. However, no other putative disease genes have yet been absolutely proven. Potential genes include MHC (HLA class II, low molecular weight proteasome [LMP], transporter associated with antigen processing (TAP), tumor necrosis factor [TNF]-alpha, and major histocompatibility complex class I chain-related gene A (MICA), as well as non-MHC genes (IL-1RA, IL-6, IL-10, and CYP2D6). Genome-wide screens have identified other chromosomal areas of interest: 1p, 2q, 6p, 9q, 10q, 16q, and 19q. However, different studies have given conflicting results. HLA-B27 itself is a serologic specificity, which encompasses 25 different alleles that encode 23 different products (proteins): HLA-B*2701 to B*2723. These alleles may have evolved from the most widespread subtype, B*2705, and two of them, B*2706 in Southeast Asia and B*2709 in Sardinia, seem not to be associated with ankylosing spondylitis. The distinction between the disease associated and nonassociated subtypes may provide clues to the actual role of B27 in disease pathogenesis.

Genetic Predisposition to Disease↗
PubMed1993

Altered CYP21 genes in HLA-haplotypes associated with congenital adrenal hyperplasia (CAH): a family study.

Disorders of the CYP21 gene, which is located within the major histocompatibility complex on the short arm of chromosome 6, are the leading causes of congenital adrenal hyperplasia (CAH). The coding gene and a highly homologous pseudogene are tandemly arranged with the two genes for the fourth component of complement (C4A and C4B). To analyse the prevalence rates of mutations of the CYP21 genes and the segregation of the CYP21 genes with their corresponding human leucocyte antigen (HLA)-haplotypes, 21 families with one or two children with the severe form of 21-hydroxylase deficiency were studied. Mutations of the CYP21 gene on their corresponding HLA-haplotype were detected by hybridisation of polymerase chain reaction (PCR)-amplified genomic DNA with sequence-specific oligonucleotides and solid phase direct sequencing. Our study has shown the following. (1) A single basepair mutation (A-->G or C-->G) within the second intron is the most frequent mutation leading to impaired 21-hydroxylase activity. This mutation is only detected in HLA-haplotypes associated with the salt-wasting form of CAH. (2) A large deletion of part or all of the CYP21 gene is associated with the HLA-haplotype A3, BW47, C6, DR7, DR53, DQ2 but is also observed in other HLA-haplotypes and can be detected by a simple rapid PCR restriction fragment length polymorphism method. (3) Two alleles of the coding CYP21 gene differing in a leucine codon within the first exon, (formerly described as a mutation associated with 21-hydroxylase deficiency) have been found with an equal distribution in patients with 21-hydroxylase deficiency, non-disease HLA-haplotypes and the local healthy controls.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Monocyte accessory cell function in patients infected with the human immunodeficiency virus.

Previous studies suggested that peripheral blood monocytes (Mo) from HIV-infected patients were poor accessory cells (AC), although most of these studies were limited by using autologous T cells as responders. Using allogeneic T cells from uninfected volunteers as responders, the current studies demonstrate that Mo from infected individuals were comparable to Mo from uninfected volunteers as AC in Con A and pokeweed mitogen-stimulated lymphocyte proliferation assays, but were inferior to normal Mo in stimulating a mixed leukocyte reaction. This deficiency was not explained by HIV Mo-induced suppression of lymphoproliferation or by death of responding CD4 lymphocytes induced by HIV transmission from infected Mo in 6-day MLR cultures. Mo from HIV-infected patients retained the ability to stimulate mumps-specific T cell lines in response to antigen, demonstrating that Mo from these individuals could process and display antigen on their cell surface in association with a functional DR molecule. Taken together these results suggest that Mo from HIV-infected patients (i) retain the ability to act as AC in T cell responses to mitogenic signals or to stimulate already activated antigen-specific T cells, but (ii) fail to stimulate resting and/or unprimed T cells in response to alloantigen and perhaps de novo antigen exposure. It is possible this Mo defect may have an adverse effect on the immune responsiveness of HIV-infected individuals.

Adult↗
PubMed1990

Enhanced capacity of females for early interferon-gamma production by natural killer-like cells following stimulation by staphylococcal enterotoxin A.

Staphylococcal enterotoxin A (SEA) induced the production of interferon-gamma (IFN-gamma) by spleen cells from ICR Swiss mice during the first 24 h of culture. Splenocytes from females produced higher levels of IFN-gamma than did those from males at 8, 12, and 16 h. By 20 h after SEA stimulation, IFN-gamma production by spleen cells from males was similar to that of females. The cell types involved in IFN-gamma production in this SEA/spleen cell system were analyzed by depletion studies. Removal of Thy-1+ cells by panning prevented production of IFN-gamma in the 24 h after SEA stimulation. In vivo depletion of asialo GM1+ (AGM1+) cells prevented production of IFN-gamma through 16 h of culture with SEA, but permitted a modest IFN-gamma response at 20 h that was similar in magnitude in both sexes. Following removal of L3T4+ and Lyt-2+ cells by panning, IFN-gamma production was detected at 12 h after SEA stimulation and maintained through 24 h of culture with cells from females producing higher levels of IFN-gamma. These data suggest that male ICR Swiss mice are deficient in the activity of Thy-1+, AGM1+, L3T4-, and Lyt-2- cells in the early (8-16 h) production of IFN-gamma following SEA stimulation of spleen cells.

Animals↗
PubMed1988

Class II human leukocyte antigen genes and T cell receptor polymorphisms in patients with rheumatoid arthritis.

Human leukocyte antigen (HLA) typing was performed in 174 patients with rheumatoid arthritis and 222 white control subjects. Increases in HLA-DR4 and HLA-DR1 were observed as in previous studies. Each of these appeared to be inherited as dominant risk factors. Southern blotting with a DR-beta probe after digestion of genomic DNA with the restriction enzyme Bam HI showed seven bands. Three of them correlated with DR4 and were increased in rheumatoid arthritis patients. Subsets of DR4 were determined by polymerase chain reaction amplification followed by hybridization with oligonucleotide probes. Dw4 was increased in rheumatoid arthritis patients, and the frequency of the other subsets appeared to be similar in rheumatoid arthritis patients and control subjects. A polymorphism associated with the T cell receptor V-beta-8 gene family was significantly increased in rheumatoid arthritis patients.

Arthritis, Rheumatoid↗
PubMed1988

HLA-DR4 and other genetic markers in rheumatoid arthritis.

In a new series of RA patients the association with HLA-DR4 was again found to be highly significant. Also increased were the DR4 associated antigens DRw53 and DQw3. Hybridization of a DQ-beta probe to Bg1 II-digested DNA showed that a variant of DQw3, characterized by a 4.3 kb fragment and related to the serological specificity TA10, was markedly increased among DR4 positive RA patients. HLA-DR1 was also increased in RA and appeared to be independent of the increase of DR4. Although the DR1 association was weaker, it was observed in both patients with and without RF. In contrast, DR4 was found to be increased significantly only in the RF positive group of patients, as previously observed. Development of RA in multiple-case families was found to be linked to the inheritance of DR4 positive haplotypes. The possible role of risk factors associated with polymorphic markers of the T-cell receptor genes was investigated. An allelic marker associated with one of the variable gene subfamilies of the beta-chain was found to be associated with RA. The results suggest that susceptibility for development of RA is influenced by alleles of the T-cell receptor in conjunction with the class II HLA factors with which the T-cell receptor interacts in the course of the immune response.

Alleles↗
PubMed1988

Allogeneic lymphocyte stimulation by human spleen. Identification of cells that are very effective for presenting class II HLA antigens.

Human spleen cells were fractionated by percoll density gradient centrifugation and by sorting in the FACS with mixtures of fluorescent antibodies against T cells, B cells, monocytes, and Sig-bearing cells. Cells responsible for powerful MLR stimulation were class II HLA antigen-positive and were concentrated in preparations depleted of all the markers listed above. These cells represented 1-2% of the initial spleen cells. They were remarkably more active than other HLA class II antigen-positive cells. The procedure described allows rapid enrichment for the responsible cells. It should be useful for further characterization of these cells and for performing studies on their function.

Antigen-Presenting Cells↗
PubMed1987

HLA-D region epitopes associated with juvenile arthritis. Recognition by alloreactive T cell clones and alloantisera.

The HLA-D region antigens DR5 (w11,w12), DRw6 (w13,w14), DRw8, DRw52, and DQw1 have previously been shown to be increased in frequency in subsets of patients with juvenile arthritis. Since the HLA-D region is complex (composed of at least 3 subregions encoding multiple molecules, each in turn presenting multiple alloantigenic epitopes), we sought to clarify whether one strongly associated factor might explain the previous findings. To search for the pertinent HLA-D region stimulatory epitopes, alloreactive T cells were primed against DR5 and DRw6 haplotypes and cloned by limiting dilution. Three T cell clones and 1 alloantiserum met the criteria for significant association with juvenile arthritis on patient testing, including DR5, DRw6, and DRw8 haplotypes. Monoclonal antibody blocking revealed that all 4 recognized epitopes on DR subregion products. For 2 of the clones, the relative risks for JA (10.5 and 9.4) were higher than the risks with any other previously described typing reagents.

Antibodies, Monoclonal↗
PubMed1987

Restriction fragment length polymorphism of the human T cell receptor alpha gene. I. Two polymorphic restriction sites localized to different regions of the gene.

Previous studies have demonstrated restriction fragment length polymorphisms (RFLP) in the vicinity of the alpha and beta genes of the human T-cell receptor. In the course of experiments designed to discover additional polymorphic restriction sites, we found a new RFLP of the T-cell alpha gene recognized by the restriction enzyme Taq I. The site was localized to the interval between the most 3' joining (J) exon and the most 5' constant (C) region exon, about 7 kb distant from the previously described Bgl II polymorphic site which mapped to the vicinity of the 3' untranslated exon. With the use of these two polymorphic markers, four Ti-alpha alleles could be identified, allowing unambiguous assignment of all Ti-alpha genes in some families. These markers may be useful in identifying possible immune response genes or disease predisposition genes associated with the genes of the T-cell receptor for antigen.

Alleles↗
PubMed1987

Antigen presentation by adherent cells from human peripheral blood. Correlation between T-cell activation and expression of HLA-DQ and -DR antigens.

The ability of cells with different amounts of HLA-DQ or -DR to support T-cell proliferation in response to foreign antigens was investigated. Adherent cells were stained with monoclonal antibodies and sorted in the fluorescence-activated cell sorter (FACS) into (a) DQ-positive and DQ-negative subsets, with monoclonal anti-DQ; or (b) subsets expressing different density of DR determinants. Expression of HLA-DQ correlated with increased density of DR. The subset of cells expressing detectable DQ and increased density of DR was found to be more efficient in presenting mumps or tetanus toxoid antigen to T cells than were the DQ-negative, low-DR density adherent cells. Similar results were obtained with primary cultures of T cells from blood and with cloned antigen-specific T-cell lines, restricted by a single DR-subregion specificity. Our results suggest that quantitative variation in DR/DQ molecules expressed on monocytes correlates with their ability to support T-cell responses to nominal antigens. It is not clear whether this is due to only class II antigen density on the surface of the accessory cells or whether other factors are involved.

Antigen-Presenting Cells↗
PubMed1986

Inability of human alveolar macrophages to stimulate resting T cells correlates with decreased antigen-specific T cell-macrophage binding.

Alveolar macrophages (AM) from the majority of human volunteers are defective antigen presenting cells (APC) in T cell proliferation assays despite the display by the cells of HLA-D region antigens. We have confirmed that AM secrete relatively little interleukin 1 (IL 1), but addition of exogenous IL 1 did not improve the capacity of AM to initiate antigen-induced T cell proliferation. Thus, the presence of HLA-D region antigens and IL 1 is not sufficient to enable an accessory cell to act as an APC. We developed a T cell-accessory cell binding assay to investigate early events in T cell activation. AM demonstrated a diminished capacity as compared with monocytes to bind antigen-specific T cell clones. Nevertheless, AM often induced proliferation of T cell clones as effectively as monocytes, indicating that antigen display was intact. The inefficiency of AM in bind T cell clones correlated with their reduced capacity to induce resting T cells to express IL 2 receptors, secrete IL 2, and proliferate in response to antigen. Indirect immunofluorescence established that similar percentages of AM and monocytes expressed LFA molecules, but the density of the molecules was greater on monocytes than AM. A role for LFA antigens in the physical binding of T cells to monocytes was demonstrated by blocking antigen-specific binding with a monoclonal antibody to LFA-1 antigen. LFA-1 antibody also blocked the low levels of specific binding between AM and T cell clones, indicating that LFA-1-ligand interactions were operative between these two cell types. These studies indicate that there are critical cell membrane characteristics that promote binding of T cells to APC in addition to T cell receptor-antigen interactions. This combination of nonspecific and specific interactions leads to avid T cell-APC binding that may be essential for activation of resting T cells. Furthermore, we postulate that the failure to AM to act as effective APC results from an inability to bind T cells efficiently.

Adult↗
PubMed1986

Recognition of class II molecules by human T cells. I. Analysis of epitopes of DR and DQ molecules in a DRw11, DRw52, DQw3 haplotype.

The HLA-D region of individuals with the DRw11, w52, DQw3 haplotype encodes multiple molecular products of three distinct subregions, DR, DP, and DQ. Since each molecule can carry multiple stimulatory epitopes, the repertoire of allogeneic T-cell responses to determinants of this haplotype can be quite large. In the present experiments, alloreactive cloned T-cell lines recognized six distinct epitopes associated with DRw11, DRw52, DQw3 haplotypes. Panel studies established that three epitopes were DRw11-like and three were DRw52-like. Blocking with monoclonal antibodies showed that two DRw11-like epitopes were carried by DR-subregion products and one DRw11-like epitope was carried by DQ-subregion molecules. DRw52-like epitopes were detected on separate DR subregion-encoded molecules. One of them carried both DRw11- and DRw52-like epitopes, the other carried two of the DRw52-like epitopes. These epitopes, which represent functional units that trigger T-cell responses, can be detected at the present time only with the methods used in this report. Conventional allogeneic T-cell responses represent the summation of responses to multiple epitopes encoded by different D-subregion genes.

Antibodies, Monoclonal↗