Publications
193 results found
Quinton ND, Smith RF, Clayton PE, et al., 1999, Leptin Binding Activity Changes with Age: The Link between Leptin and Puberty1, The Journal of Clinical Endocrinology & Metabolism, Vol: 84, Pages: 2336-2341, ISSN: 0021-972X
<jats:p>The timing of the physical transition from child to adult is determined by a biological clock that switches off the pituitary gonadal axis during infancy until puberty. Body composition (and in particular, fat mass), through leptin, are critical signals to this clock. However, no direct relationship between leptin and puberty has been demonstrated. Leptin is bound in the circulation by a high-affinity binding protein, which has been identified as a soluble leptin receptor. We found circulating levels of leptin binding activity (LBA) to be low at birth, to be high in the prepubertal years, to fall through puberty, and then to remain stable during adult life. LBA correlated with pubertal status in both boys and girls. We postulate that the fall in LBA, associated with increasing age and puberty, reflects a reduction in expression of truncated leptin receptors, and leptin is then available to the full-length receptor, which transmits the biological signal for leptin. The high levels of LBA occur during the years when the pituitary gonadal axis is quiescent. Thus, the change in LBA could explain how leptin regulates puberty.</jats:p>
Quinton ND, Li TC, Ross RJM, et al., 1999, Expression of leptin receptor isoforms in the human endometrium, HUMAN REPRODUCTION, Vol: 14, Pages: 370-370, ISSN: 0268-1161
Quinton ND, Smith RF, Clayton PE, et al., 1999, Leptin binding activity changes with age: the link between leptin and puberty, J Clin Endocrinol Metab, Vol: 84, Pages: 2336-2341, ISSN: 0021-972X
The timing of the physical transition from child to adult is determined by a biological clock that switches off the pituitary gonadal axis during infancy until puberty. Body composition (and in particular, fat mass), through leptin, are critical signals to this clock. However, no direct relationship between leptin and puberty has been demonstrated. Leptin is bound in the circulation by a high-affinity binding protein, which has been identified as a soluble leptin receptor. We found circulating levels of leptin binding activity (LBA) to be low at birth, to be high in the prepubertal years, to fall through puberty, and then to remain stable during adult life. LBA correlated with pubertal status in both boys and girls. We postulate that the fall in LBA, associated with increasing age and puberty, reflects a reduction in expression of truncated leptin receptors, and leptin is then available to the full-length receptor, which transmits the biological signal for leptin. The high levels of LBA occur during the years when the pituitary gonadal axis is quiescent. Thus, the change in LBA could explain how leptin regulates puberty.
Quinton ND, Laird SM, Okon MA, et al., 1999, Serum leptin levels during the menstrual cycle of healthy fertile women, Br J Biomed Sci, Vol: 56, Pages: 16-19, ISSN: 0967-4845
Leptin is a protein, produced by adipose tissue, which has cytokine and hormonal properties. Serum leptin levels can be considered as a measure of body fat mass, and are involved in regulation of body weight. Previous studies suggest that leptin may have an additional role in reproduction, and there is also evidence for involvement in the hypothalamic-pituitary-gonadal axis. In this study, we investigate the possible changes in serum leptin concentration throughout the menstrual cycle. Samples were collected from apparently healthy, fertile women at different stages in their menstrual cycle, timed precisely according to the luteinising hormone (LH) surge. Mean serum leptin levels were significantly higher in the luteal phase (median 11.4 ng/mL) than in the follicular phase (median 10.0 ng/mL) (P < 0.001). In addition, mean serum leptin levels correlated with body mass index (r = 0.54, P < 0.05), but showed no correlation with luteal-phase progesterone levels. Results showed that levels of serum leptin vary during the menstrual cycle, and add to the mounting evidence that leptin has a role in reproduction. These fluctuations should be taken into account whenever studies are performed using female subjects.
Blakemore AIF, Lee AJ, Quinton ND, et al., 1998, Association of GLN223ARG polymorphism in the leptin receptor gene with serum leptin levels and BMI in postmenopausal Caucasian women, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 6, Pages: 107-107, ISSN: 1018-4813
- Author Web Link
- Cite
- Citations: 1
Tarlow JK, Cork MJ, Clay FE, et al., 1997, Association between interleukin-1 receptor antagonist (IL-1ra) gene polymorphism and early and late-onset psoriasis, Br J Dermatol, Vol: 136, Pages: 147-148, ISSN: 0007-0963
Maskill JK, Laird SM, Okon M, et al., 1997, Stability of serum interleukin-10 levels during the menstrual cycle, Am J Reprod Immunol, Vol: 38, Pages: 339-342, ISSN: 1046-7408
PROBLEM: Menstrual cycle-associated variability in the circulating levels of several cytokines can be a confounding factor in measurements of in vivo cytokine levels in clinical studies. Since pregnancy-associated increases in interleukin-10 (IL-10) levels are well documented, we have investigated the variability in serum levels of IL-10 in healthy women at different stages of the menstrual cycle to ascertain whether this is a problem in comparative studies of circulating IL-10 levels. METHOD OF STUDY: We obtained fifty-four successive serum samples at points in the menstrual cycles of 12 healthy fertile women, precisely timed by measurement of the luteinizing hormone surge, and measured the interleukin-10 levels. RESULTS: Levels of IL-10 in successive serum samples from each woman taken on days LH - 7 (that is seven days prior to LH surge), LH - 4, LH + 1, LH + 7, and LH + 10 showed that IL-10 does not vary in a systematic way during the menstrual cycle. CONCLUSION: These results validate the sampling of women in studies of IL-10 levels in various clinical situations and establish that these levels are not dependent on menstrual cycle dates. They also suggest that menstrual cycle-related changes in IL-1 are not mediated by IL-10. The rise in progesterone in the luteal phase of the menstrual cycle is not mirrored by a rise in the circulating IL-10 level, which implies either that the pregnancy-associated rise is not related to progesterone or that it is only observed at the higher progesterone levels in pregnancy.
Maskill JK, Gordon C, Blakemore AIF, 1996, Elevated serum interleukin-10 is associated with increased activity of systemic lupus erythematosus., IMMUNOLOGY, Vol: 89, Pages: BB295-BB295, ISSN: 0019-2805
Blakemore AIF, Laird S, Okon M, et al., 1996, Serum interleukin-10 levels do not alter during the menstrual cycle, IMMUNOLOGY, Vol: 89, Pages: OZ261-OZ261, ISSN: 0019-2805
Blakemore AIF, Cox A, Gonzalez A-M, et al., 1996, Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus, Human Genetics, Vol: 97, Pages: 369-374, ISSN: 0340-6717
Blakemore AI, Cox A, Gonzalez AM, et al., 1996, Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus, Hum Genet, Vol: 97, Pages: 369-374, ISSN: 0340-6717
We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN*2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.
Blakemore AI, Watson PF, Weetman AP, et al., 1995, Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene., The Journal of Clinical Endocrinology & Metabolism, Vol: 80, Pages: 111-115, ISSN: 0021-972X
Cork MJ, Tarlow JK, Clay FE, et al., 1995, An allele of the interleukin-1 receptor antagonist as a genetic severity factor in alopecia areata, J Invest Dermatol, Vol: 104, Pages: 15S-16S, ISSN: 0022-202X
Blakemore AI, Watson PF, Weetman AP, et al., 1995, Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene, J Clin Endocrinol Metab, Vol: 80, Pages: 111-115, ISSN: 0021-972X
The proinflammatory cytokine, interleukin-1 (IL-1), has been implicated in the pathogenesis of several autoimmune and inflammatory diseases. One of its natural inhibitors, IL-1 receptor antagonist, is a potent antiinflammatory agent. We have previously described genetic associations between an allele of the IL-1 receptor antagonist gene (IL1RN*2) and several autoimmune and inflammatory diseases. In the present study, we tested the association of this polymorphism with thyroid diseases. We genotyped 2 separate cohorts (total of 100 patients) with Graves' disease and 58 patients with Hashimoto's thyroiditis and compared IL1RN*2 frequencies with those in 261 ethnically matched controls. There was a significant increase in IL1RN*2 frequency and carriage rate in Graves' disease, but this was not associated with thyroid antibody levels, T4 levels, thyroid-associated ophthalmopathy, or outcome after antithyroid drug treatment. In contrast, there was no difference in the frequency of IL1RN*2 between patients with Hashimoto's thyroiditis and the control group. Whether the IL1RN polymorphism makes a direct functional contribution to the pathogenesis of Graves' disease or is acting as a marker for a linked gene is being investigated.
CLAY FE, CORK MJ, TARLOW JK, et al., 1994, ASSOCIATION OF THE INTERLEUKIN ONE RECEPTOR ANTAGONIST GENE POLYMORPHISM WITH LICHEN-SCLEROSUS, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 103, Pages: 408-408, ISSN: 0022-202X
Clay FE, Cork MJ, Tarlow JK, et al., 1994, Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus, Hum Genet, Vol: 94, Pages: 407-410, ISSN: 0340-6717
Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1 alpha and IL-1 beta, and therefore is a powerful endogenous anti-inflammatory molecule. The gene encoding IL-1ra (designated IL-1RN) has a variable number tandem repeat polymorphism in intron 2. There are five alleles of the gene corresponding to 2, 3, 4, 5 and 6 repeats of an 86-bp sequence. We have determined allele frequencies in a control population and a group of 78 patients with lichen sclerosus. The frequency of one of the alleles is related to increasing disease severity. Thus, IL-1RN may be a candidate gene or severity factor for lichen sclerosus or may possibly be a linked marker to another, as yet undefined, gene.
Blakemore AI, Tarlow JK, Cork MJ, et al., 1994, Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus, Arthritis Rheum, Vol: 37, Pages: 1380-1385, ISSN: 0004-3591
OBJECTIVE: We have previously described associations between an allele of the interleukin-1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE). METHODS: Eighty-one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction. RESULTS: We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions. CONCLUSION: We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.
Tarlow JK, Clay FE, Cork MJ, et al., 1994, Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene, J Invest Dermatol, Vol: 103, Pages: 387-390, ISSN: 0022-202X
One of the most potent pro-inflammatory mediators is the early-acting cytokine interleukin-1. Its actions are regulated by a structurally related anti-inflammatory cytokine known as the interleukin-1 receptor antagonist. We have previously characterized a DNA polymorphism in this gene (IL-1rn) and have found associations between allele 2 and several chronic inflammatory diseases. In the present study, we tested the frequency of allele 2 of the IL-1rn gene in 90 patients with alopecia areata compared with 261 healthy controls. There was a significant association between allele 2 of the polymorphism and the severity of alopecia areata. The frequency of allele 2 increased from 24.1% in the control population to 25.9% in patchy alopecia areata, 36.1% in alopecia totalis, and 47.2% in alopecia universalis (p = 0.005). This severity association is similar to that found in other epithelial-related diseases, including inflammatory bowel disease, lichen sclerosus, and systemic lupus erythematosus.
Cork MJ, Tarlow JK, Blakemore AI, et al., 1993, Psoriasis and interleukin-1. A translation., J R Coll Physicians Lond, Vol: 27, ISSN: 0035-8819
CORK MJ, TARLOW JK, BLAKEMORE AIF, et al., 1993, GENETICS OF INTERLEUKIN ONE RECEPTOR ANTAGONIST IN INFLAMMATORY SKIN DISEASES, CLINICAL RESEARCH, Vol: 41, Pages: A179-A179, ISSN: 0009-9279
MANSFIELD JC, TARLOW JK, HOLDEN H, et al., 1993, ULCERATIVE-COLITIS IS ASSOCIATED WITH THE RARER ALLELE OF INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE, GASTROENTEROLOGY, Vol: 104, Pages: A736-A736, ISSN: 0016-5085
- Author Web Link
- Cite
- Citations: 1
CORK MJ, MEE JB, TARLOW JK, et al., 1993, INTERLEUKIN ONE RECEPTOR ANTAGONIST POLYMORPHISM - ALLELIC ASSOCIATION WITH INFLAMMATORY DERMATOSES, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 100, Pages: 448-448, ISSN: 0022-202X
- Author Web Link
- Cite
- Citations: 2
CORK MJ, TARLOW JK, BLAKEMORE AIF, et al., 1993, GENETICS OF INTERLEUKIN ONE RECEPTOR ANTAGONIST IN INFLAMMATORY SKIN DISEASES, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 100, Pages: 522-522, ISSN: 0022-202X
- Author Web Link
- Cite
- Citations: 7
Cork MJ, Tarlow JK, Blakemore AI, et al., 1993, Psoriasis and interleukin-1. A translation, J R Coll Physicians Lond, Vol: 27, ISSN: 0035-8819
Bailly S, di Giovine FS, Blakemore AI, et al., 1993, Genetic polymorphism of human interleukin-1 alpha, Eur J Immunol, Vol: 23, Pages: 1240-1245, ISSN: 0014-2980
Interleukin-1 alpha (IL-1 alpha) has been implicated in the pathogenesis of infectious, autoimmune and inflammatory diseases. There is, however, very little information on the cis-acting sequences involved in IL-1 alpha regulation or whether there is any variation in the structure of the gene. It is known that intron 6 of IL-1 alpha shows a 5 x 46 bp tandem repeat in the genomic sequence. We have studied this region of the gene. Amplification by polymerase chain reaction showed different sized products from different individuals, most being of higher molecular weight than the expected size of 620 bp. Sequencing demonstrated that the polymorphism was due to a variable number of repeats of the 46 bp sequence. This was confirmed by restriction fragment length analysis of genomic DNA. Altogether, 72 unrelated individuals were tested and 6 alleles ranging from 5 to 18 repeats were found, the most frequent allele (62%) containing 9 repeats. This polymorphism may be of interest in gene function, since each repeat contains three potential binding sites for transcriptional factors: an SP1 site, a viral enhancer element and a glucocorticoid-responsive element. The latter, at least, demonstrates site-specific protein binding by electromobility shift assay. The functional significance of the polymorphism and its allelic frequency in inflammatory and autoimmune diseases are currently under investigation.
Tarlow JK, Blakemore AI, Lennard A, et al., 1993, Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat, Hum Genet, Vol: 91, Pages: 403-404, ISSN: 0340-6717
We have investigated the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene and identified two new alleles of the system. We have shown that the polymorphism is caused by the variable copy number of an 86-bp sequence, by using the polymerase chain reaction and primers immediately flanking the repeat region, and by direct sequencing. The repeat region contains three potential protein-binding sites and therefore the variable copy number may have functional significance.
WILSON AG, DEVRIES N, DIGIOVINE FS, et al., 1992, STRONG LINKAGE OF A NOVEL POLYMORPHISM IN TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) WITH HLA CLASS-II (DR3, DR4 AND THE 3RD HYPERVARIABLE REGION OF DR-BETA-1), ARTHRITIS AND RHEUMATISM, Vol: 35, Pages: S287-S287, ISSN: 0004-3591
di Giovine FS, Takhsh E, Blakemore AI, et al., 1992, Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta), Hum Mol Genet, Vol: 1, ISSN: 0964-6906
Curtis D, Blakemore AI, Engel PC, et al., 1992, Medium chain acyl-CoA dehydrogenase deficiency in the United Kingdom, Prog Clin Biol Res, Vol: 375, Pages: 489-494, ISSN: 0361-7742
Wilson AG, di Giovine FS, Blakemore AI, et al., 1992, Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product, Hum Mol Genet, Vol: 1, ISSN: 0964-6906
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.