Pheochromocytomas are neural crest–derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1α. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1α activity in tumors.

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Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear. Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population. The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function.

Osteoporosis represents a major health problem, resulting in substantial increases in health care costs. There is an unmet need for a cost-effective technique that can measure bone properties without the use of ionizing radiation. The present study reports design, construction, and testing of a safe, and easy to use radiofrequency device to detect osteoporotic bone conditions. The device uses novel on-body antennas contacting the human wrist under an applied, operator-controlled pressure. For the dichotomous diagnostic test, we selected 60 study participants (23–94 years old, 48 female, 12 male) who could be positively differentiated between healthy and osteopenic/osteoporotic states. The band-limited integral of the transmission coefficient averaged for both wrists, multiplied by age, and divided by BMI has been used as an index. For a 100 MHz frequency band centered about 890–920 MHz, the maximum Youden’s J index is 81.5%. Both the sensitivity and specificity simultaneously reach 87% given the calibration device threshold tolerance of ±3%. Our approach correlates well with the available DXA measurements and has the potential for screening patients at risk for fragility fractures, given the ease of implementation and low costs associated with both the technique and the equipment. The inclusion of radiofrequency transmission data does add supplementary useful information to the available clinical risk factors.