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)

More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis. In an earlier analysis [H. Spiess and C. W. Mays, in Radiation Carcinogenesis. (C. L. Sanders et al., Eds.) pp. 437-450. USAEC Symposium Series 29, CONF-720505, 1973] it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas. The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients. In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods. A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test. In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose. A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment. The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months. This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma.
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PMID:The reverse protraction factor in the induction of bone sarcomas in radium-224 patients. 223 14

The risk of developing a tumor of the nervous system in humans is analysed in several studies of populations, exposed to ionising radiation for medical reasons, or exposed to military or occupational radiation. The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia). The type of radiation-induced tumors is variable, but meningioma is more frequent after low doses and glioma and sarcoma after higher doses used in the treatment of neoplastic diseases. A dose-effect relationship appeared between the risk of tumor of the nervous system and the radiation dose. The risk was higher when radiation was delivered at a younger age. Much less data are available after radiotherapy in the adulthood, but an increased risk of cerebral tumor appears in the series of ankylosing spondylitis patients. As for the exposures to radiodiagnosis exams, the main problem is the risk of cerebral tumor in children whose mother has undergone abdominal or pelvic X-rays during pregnancy. No risk of neurologic tumor was found in the A-bomb survivors irradiated at Hiroshima and Nagasaki. Occupational exposure to ionising radiation has been incriminated in the first radiologists exposed to high doses. In nuclear industry workers, the results of epidemiological studies are contradictory and at the present time it is not possible to link their radiologic exposure with a risk of tumor of the nervous system. In populations living near nuclear plants, mortality due to tumors of the nervous system was not increased.
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PMID:[Radiation-induced tumors of the nervous system in man]. 808 Oct 35

A revision of bone tumor pathology in patients treated with multiple injections of the short-lived alpha-particle emitter radium-224, predominantly for tuberculosis and ankylosing spondylitis, revealed an unexpectedly high proportion of bone sarcomas of the fibrous connective tissue type. This included the first case of malignant fibrous histiocytoma of bone described after internal irradiation. A comparison of bone tumor types in the radium-224 patients and bone sarcoma after incorporation of radium-226 and radium-228 and external irradiation and in tumors arising at sites of pre-existing bone lesions showed the same spectrum of tumors. The high incidence of bone tumors of the fibroblastic and fibrohistiocytic type was observed in all these "secondary" bone sarcomas. These results suggest that a close histogenetic relationship exists between disorder of the local milieu caused by deterministic radiation damage accompanied by disturbances of the remodeling process. The reactive proliferation of the predominantly fibroblastic tissue could be the presumptive origin of these special types of radiation-induced bone sarcomas.
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PMID:Pathology of radium-induced bone tumors: new aspects of histopathology and histogenesis. 1056 27

Between 1945 and 1955, several thousand patients were injected with Peteosthor, a preparation containing Radium-224 (Ra), as treatment for bone tuberculosis or ankylosing spondylitis. Ra, like Pu, is a bone seeking nuclide. During the course of early experimental work it became clear in 1948 that the short lived alpha-emitter Ra concentrates predominantly in the growing zones of the bones. Consequently, I released strong official warnings, at the 1950 German Congress of Orthopedics, against Peteosthor, and especially against its administration to juvenile patients-still in their period of growth. Epidemiological investigations were then initiated on a study population that comprises 899 persons (including 217 children or juveniles) who received injections of Ra. The study has now been conducted for a follow-up period of over 60 y. The most striking detrimental health effect following Ra injections are a large number of malignant bone tumors that occurred predominantly in childhood. This finding was the reason for my invitation to the first conference on "Delayed Effects of Bone seeking Radionuclides" in Sun Valley, ID, in September 1967, a meeting that was organized by Charles Mays. I reported on 50 Ra-induced bone tumors in children and adults, growth disturbances, osteochondroma, and cataracts, concluding that the younger the age at Ra injection, the more severe the late effects. Up to now 57 malignant bone tumors have been observed while less than one case would have been expected. The peak occurred 8 y after the first Ra injection and the last bone sarcoma arose 46 y after injection. A total of 270 non-skeletal malignant diseases were observed against a statistical expectation of 192 cases, the excess risk of mammary cancers in those treated in childhood being particularly striking. In the past two years increases of non-cancer diseases have become apparent in the exposed group compared to a control group of 166 living members with no exposure to Ra. Although 124 study group members are still alive, only the 81 members with ages at or below the maximum age in the control group were included in this comparison in order to attain approximate age matching. The breakdown of these diseases is kidney insufficiency, 12 (15%) study group members vs. 3 (2%) controls, where 5 (6%) study group members required dialysis vs. 2 (1%) controls; thyroid disease (struma nodosa), 28 (35%) study group members vs. 29 (17%) controls; heart attack, 8 (10%) study group members vs. 4 (2%) controls; coronary heart disease, 9 (11%) study group members vs. 8 (5%) controls.
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PMID:Life-span study on late effects of 224Ra in children and adults. 2069 88

A variety of osteoarticular conditions possess an underlying genetic aetiology. Large-scale genome-wide association studies have identified several genetic loci associated with osteoarticular conditions, but were unable to fully account for their estimated heritability. Epigenetic modifications including DNA methylation, histone modification, nucleosome positioning, and microRNA expression may help account for this incomplete heritability. This articles reviews insights from epigenetic studies in osteoarticular diseases, focusing on osteoarthritis, but also examines recent advances in rheumatoid arthritis, osteoporosis, systemic lupus erythematosus (SLE), ankylosing spondylitis, and sarcoma. Genome-wide methylation studies are permitting identification of novel candidate genes and molecular pathways, and the pathogenic mechanisms with altered methylation status are beginning to be elucidated. These findings are gradually translating into improved understanding of disease pathogenesis and clinical applications. Functional studies in osteoarthritis, rheumatoid arthritis, and SLE are now identifying downstream molecular alterations that may confer disease susceptibility. Epigenetic markers are being validated as prognostic and therapeutic disease biomarkers in sarcoma, and clinical trials of hypomethylating agents as treatments for sarcoma are being conducted. In concert with advances in throughput and cost-efficiency of available technologies, future epigenetic research will enable greater characterisation and treatment for both common and rare osteoarticular diseases.
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PMID:Epigenetics of osteoarticular diseases: recent developments. 2581 37