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Proton-decoupled (31)P and (1)H MRS was used to quantify markers of membrane synthesis and breakdown in eight pediatric patients with untreated brain tumors and in six controls. Quantitation of these compounds in vivo in humans may provide important indicators for tumor growth and malignancy, tumor classification, and provide prognostic information. The ratios of phosphoethanolamine to glycerophosphoethanolamine (PE/GPE) and phosphocholine to glycerophosphocholine (PC/GPC) were significantly higher in primitive neuroectodermal tumors (PNET) (16.30 +/- 5.73 and 2.97 +/- 0.93) when compared with controls (3.42 +/- 1.62, P < 0.0001 and 0.45 +/- 0.13, P < 0.0001) and with other tumors (3.93 +/- 3.42, P < 0.001 and 0.65 +/- 0.30, P < 0.0001). Mean PC/PE was elevated in tumors relative to controls (0.48 +/- 0.11 versus 0.24 +/- 0.05, P < 0.001), but there was no difference between PNET and other tumors. Total choline concentration determined with quantitative (1)H MRS was significantly elevated (4.78 +/- 3.33 versus 1.73 +/- 0.56 mmol/kg, P < 0.05), whereas creatine was reduced in tumors (4.89 +/- 1.83 versus 8.28 +/- 1.50 mmol/kg, P < 0.05). A quantitative comparison of total phosphorylated cholines (PC+GPC)/ATP measured with (31)P MRS and total choline measured with (1)H MRS showed that in tumors a large fraction of the choline signal (>54 +/- 36%) was not accounted for by PC and GPC. The fraction of unaccounted choline was particularly large in PNET (>78 +/- 7%). The pH of tumor tissue was higher than the pH of normal brain tissue (7.06 +/- 0.03 versus. 6.98 +/- 0.03, P < 0.001)., (Copyright 2004 Wiley-Liss, Inc.)

The inner ear develops from a simple epithelium (otic placode) into the complex structures specialized for balance (vestibule) and sound (cochlea) detection. Abnormal vestibular and cochlear development is associated with many birth defects. During recent years, considerable progress has been made in understanding the molecular bases of these conditions. To determine the biological function of two closely related GTPase activating proteins for the Cdc42/Rac GTPases, Abr and Bcr, we generated a mouse strain deficient in both of these proteins. Double null mutant mice exhibit hyperactivity, persistent circling, and are unable to swim. These phenotypes are typically found in mice with vestibular defects. Indeed, adult double null mutants display abnormal dysmorphic structures of both the saccule and utricle. Moreover, a total loss of otoconia can be seen in the utricle, whereas in the saccule, otoconia are either missing or their number is drastically decreased and they are abnormally large. Interestingly, both the cochlea and semicircular canals are normal and the double null mutant mice are not deaf. These data demonstrate that Abr and Bcr play important complementary roles during vestibular morphogenesis and that a function of Cdc42/RacGAPs and, therefore, that of the small Rho-related GTPases is critically important for balance and motor coordination., (Copyright 2002 Wiley-Liss, Inc.)