Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sacroiliac uptake ratios based on 99Tcm methylene diphosphonate images were calculated in 14 patients with ankylosing spondylitis, 23 patients with non-specific backache, 33 patients with inflammatory bowel disease (ulcerative colitis 19, Crohn's disease 14) and 33 control subjects. Twenty-eight of the control subjects were patients referred from a breast cancer clinic. In the control subjects, and in 20 patients with inflammatory bowel disease who did not have back pain, sacroiliac ratios decreased significantly with increasing age (p less than 0.001 and p less than 0.01 respectively). Sacroiliac uptake ratios were significantly higher in ankylosing spondylitis than in patients with non-specific backache. Seven of the 14 patients with ankylosing spondylitis had higher sacroiliac ratios than any recorded in the control subjects. Eleven patients with inflammatory bowel disease had abnormally high sacroiliac uptake ratios; ten of these patients had back pain. Increased sacroiliac joint uptake in such patients may reflect early sacroiliitis. No relationship was detected between sacroiliac uptake and the activity of the bowel disease. Sacroiliac uptake ratios were significantly higher in the inflammatory bowel disease patients suffering from back pain than in age and sex matched patients with (a) inflammatory bowel disease but no back pain or (b) non-specific backache.
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PMID:Sacroiliac joint uptake ratios in inflammatory bowel disease: relationship to back pain and to activity of bowel disease. 621 68

Predominantly from 1945 to 1955, a group of patients in Germany was treated with multiple injections of the short-lived alpha-particle emitter (224)Ra. The patients suffered from ankylosing spondylitis, tuberculosis and in a few cases from other diseases. The "Spiess study" (study I) follows up the health of 899 of these patients; it includes most of the patients who were treated with high doses (mean bone surface dose: 30 Gy, mean specific activity: 0.66 MBq/kg), and nearly all of those treated under the age of 21 years. The most striking consequence of the (224)Ra injections was the occurrence of 56 malignant bone tumors. They appeared in a temporal wave that peaked around 8 years after exposure. A new analysis was recently performed, because a reassessment of the dosimetry resulted in changed bone surface doses, especially for the patients treated at younger ages. Averaged over all ages at exposure, the estimated risk coefficient is in general agreement with earlier analyses. However, there is now an increase in bone tumor risk that is significantly greater for younger ages at exposure. The earlier finding of an inverse protraction factor is confirmed. During the most recent years of follow-up, a significant excess of nonskeletal solid malignancies has become manifest. In 1998, a significant increase of breast cancer incidence, of soft tissue malignancies, of thyroid carcinomas, and of liver, kidney and bladder cancer was found. An eightfold increased risk of mammary cancers in those treated at a young age is particularly striking. Equally notable are two cases of breast cancer in male patients. To identify potential confounders, a control group of tuberculosis patients not treated with (224)Ra was established. The comparison confirms that the (224)Ra treatment is responsible for most of the excess of mammary cancer.
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PMID:Malignancies in patients treated with high doses of radium-224. 1056 25

This study is comprised of 1577 ankylosing spondylitis patients from 9 German hospitals who have been treated with multiple injections of (224)Ra. The majority of the patients, most of them treated in the years 1948-1975, received one series of 10 weekly intravenous injections of about 1 MBq of (224)Ra each. This dose leads to a mean absorbed dose due to alpha-particle radiation of 0.56 Gy to the marrow-free skeleton of a 70- kg man (mean bone surface dose of about 5 Gy). To provide comparative information on causes of death and on health effects possibly related to the basic disease itself, a control group of 1462 ankylosing spondylitis patients with roughly the same age distribution has been established. By the end of 1998, 649 patients in the exposed group and 762 control patients had died. Among other observations, it is of particular interest that 13 cases of leukemia in the exposed group have been observed. This is a highly significant excess (P < 0.001) compared to a standard population, but only a marginally significant excess in comparison to the seven cases observed in the control group. Subclassification of the leukemias shows a clear preponderance of the myeloid leukemias in the exposed group (8 cases observed compared to 1.7 cases expected, P < 0.001), whereas in the control group the observed cases are within the expected range for myeloid leukemia (3 cases observed compared to 2.2 cases expected, P = 0.3). The (224)Ra cohort of the earlier study (higher-dose group) has provided a risk coefficient that predicts about 8 excess malignant bone tumors for the irradiated cohort in this study. In actuality, 4 cases of malignant tumors in the skeleton have been observed so far. However, excess of breast cancer has not been observed in either the irradiated or the control group, which is in contrast to the findings in the earlier (224)Ra cohort of Study I.
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PMID:Late effects in ankylosing spondylitis patients treated with 224Ra. 1056 26

The androgen receptor gene (AR) contains a domain which includes a variable number of CAG sequences and alleles with low numbers of CAG repeats show high transactivation activity when complexed with testosterone. The ratio of 2nd and 4th digit length (2D:4D) is negatively correlated with phenotypic effects of testosterone. Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer. This suggests that CAG number and 2D:4D are correlated i.e. low CAG number and low 2D:4D indicate high activation of androgen-responsive genes. Findings from AR studies predict that low 2D:4D will be associated with prostate and hepatocellular cancer, urolithiasis, ADHD, ankylosing spondylitis, spontaneous abortion, and polycystic ovaries, while high 2D:4D will be associated with motor neuron diseases and endometrial cancer. Findings from 2D:4D studies predict that short CAG length will be common in autism and Asperger's syndrome, while high numbers of CAG repeats will be found in men who are prone to early myocardial infarction.
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PMID:The ratio of 2nd to 4th digit length: a proxy for transactivation activity of the androgen receptor gene? 1220 64

In the course of 2002, several new studies were published confirming the efficacy of bisphosphonate drugs in fracture prevention in patients with osteoporosis. Further evidence was provided of their long duration of action, making intermittent administration possible. The potent bisphosphonate zoledronate can be given at intervals of as long as 1 year and produces changes in bone density and in markers of bone turnover comparable with those seen with conventional daily oral dosing with alendronate or risedronate. If such regimens are proven to prevent fractures, their convenience is likely to result in their widespread adoption and potentially an increase in compliance with these medications. Further evidence has been presented documenting the value of bisphosphonates in preventing the skeletal complications of malignancy, and possibly in reducing mortality in patients with breast cancer. The role of bisphosphonates in osteogenesis imperfecta was further confirmed, and novel roles in ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy were suggested.
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PMID:Bisphosphonates: new indications and methods of administration. 1281 75

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.
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PMID:The management of secondary osteoporosis. 1630 Nov 95

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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PMID:Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. 1795 73

Recent large-scale genome-wide association (GWA) studies of SNP variations captured many thousands individual genetic profiles of H. sapiens and facilitated identification of significant genetic traits which are highly likely to influence the pathogenesis of several major human diseases. Here we apply the integrative genomics principles to interrogate relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 15 major human disorders, namely bipolar disease (BD); rheumatoid arthritis (RA); coronary artery disease (CAD); Crohn's disease (CD); type 1 diabetes (T1D); type 2 diabetes (T2D); hypertension (HT); ankylosing spondylitis (AS); Graves' disease (autoimmune thyroid disease; AITD); multiple sclerosis (MS); breast cancer (BC); prostate cancer (PC); systemic lupus erythematosus (SLE); vitiligo-associated multiple autoimmune disease (VIT); and ulcerative colitis (UC). We selected for sequence homology profiling a set of approximately 250 SNPs which were unequivocally associated with common human disorders based on multiple independent studies of 220,124 individual samples comprising 85,077 disease cases and 129,506 controls. Our analysis reveals a systematic primary sequence homology/complementarity-driven pattern of associations between disease-linked SNPs, microRNAs and protein-coding mRNAs defined here as a human disease phenocode. We utilize this approach to draw SNP-guided microRNA maps of major human diseases and define a consensus disease phenocode for fifteen major human disorders. A consensus disease phenocode comprises 72 SNPs and 18 microRNAs with an apparent propensity to target mRNA sequences derived from a single protein-coding gene, KPNA1. Each of microRNAs in this elite set appears linked to at least three common human diseases and has potential protein-coding mRNA targets among the principal components of the nuclear import pathway. We confirmed the validity of our findings by analyzing independent sets of most significant disease-linked SNPs and demonstrating statistically significant KPNA1-gene expression phenotypes associated with human genotypes of CD, BD, T2D and RA populations. Our analysis supports the idea that variations in DNA sequences associated with multiple human diseases may affect phenotypes in trans via non-protein-coding RNA intermediaries interfering with functions of microRNAs and defines the nuclear import pathway as a potential major target in 15 common human disorders.
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PMID:An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway. 1871 69

A 72-year-old male with a 4-year history of TNFalpha antagonist therapy (infliximab and etanercept) for ankylosing spondylitis was diagnosed with breast cancer. He had a family history of breast cancer. The low incidence and considerable severity of breast cancer in males, genetic risk factors, and potential role for TNFalpha antagonist therapy are discussed.
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PMID:Breast cancer in a male with ankylosing spondylitis treated with TNFalpha antagonists. 1945 92

Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.
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PMID:Immunology Update: Biologics. 2786 38


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