The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator.

Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have established a cell culture model consisting of four stably transfected cell lines and analysed the functional properties of the SHOX protein on a molecular level. Results show that the SHOX-encoded protein is located exclusively within the nucleus of a variety of cell lines, including U2Os, HEK293, COS7 and NIH 3T3 cells. In contrast to this cell-type independent nuclear translocation, the transactivating potential of the SHOX protein on different luciferase reporter constructs was observed only in the osteogenic cell line U2Os. Since C-terminally truncated forms of SHOX lead to LWS and idiopathic short stature, we have compared the activity of wild-type and truncated SHOX proteins. Interestingly, C-terminally truncated SHOX proteins are inactive with regards to target gene activation. These results for the first time provide an explanation of SHOX-related phenotypes on a molecular level and suggest the existence of qualitative trait loci modulating SHOX activity in a cell-type specific manner.     

Bone cancer incidence rates in New York State: time trends and fluoridated drinking water.

BACKGROUND: Recent animal studies of the potential carcinogenicity of fluoride prompted an examination of bone cancer incidence rates. METHODS: Trends in the incidence of primary bone cancers, including the incidence of osteosarcomas were examined among residents of New York State, exclusive of New York City. Average annual osteosarcoma incidence rates in fluoridated and non-fluoridated areas were also compared. RESULTS: Among persons less than 30 years of age at diagnosis, bone cancer incidence among males demonstrated a significant increase since 1955, while incidence among females has remained unchanged. A significant decrease in bone cancer incidence rates since 1955 was observed among both males and females age 30 years and over at time of diagnosis. Osteosarcoma incidence rates have remained essentially unchanged since 1970, among both younger and older males and females. The average annual age adjusted incidence of osteosarcomas (1976-1987) in areas served by fluoridated water supplies was not found to differ from osteosarcoma incidence rates in non-fluoridated areas. CONCLUSIONS: These data do not support an association between fluoride in drinking water and the occurrence of cancer of the bone.     

Determinants of late stage diagnosis of breast and cervical cancer: the impact of age, race, social class, and hospital type

Previous studies of the relationship between cancer stage, age, and race have not controlled for social class and health care setting. Logistic regression analyses, using information from the New York State Tumor Registry and area-level social class indicators, demonstrated that, in New York City, older Black, lower class women in public hospitals were 3.75 and 2.54 times more likely to have late stage breast or cervical cancer, respectively, than were younger White, high social class women in non-public hospitals.     

Internal carotid artery occlusion: effect of contralateral flow reduction in inducing symptoms

Cerebral ischemic attacks ipsilateral to an occluded internal carotid artery (ICA) continue in more than 16% of patients. With common carotid artery compression on the side of ICA occlusion in 53 patients, the mean (+/- SEM) ophthalmic systolic pressure/brachial systolic pressure (OSP/BSP) ratio fell from 0.58 +/- 0.013 to 0.42 +/- 0.020 (p less than 0.001), without any cerebral ischemic symptoms. Compression of the contralateral patent common carotid artery resulted in the ophthalmic systolic pressure/brachial systolic pressure ratio dropping from 0.67 +/- 0.012 to 0.29 +/- 0.017 (p less than 0.001) on the patient side and from 0.58 +/- 0.013 to 0.48 +/- 0.018 (p less than 0.001). Twenty-six of 53 patients (49%) developed ischemic symptoms in response to compression of the remaining patent ICA system. In contrast, only 8 of 122 patients (6.5%) without ICA occlusion developed any symptoms of cerebral dysfunction (p less than 0.001). This study suggests embolic events rather than flow reduction may be of greater importance in the production of new symptoms and that contralateral flow is critical to normal cerebral function in half the population with ICA occlusion.