The amino terminus of the glial glutamate transporter GLT-1 interacts with the LIM protein Ajuba

We have identified a cytoplasmic LIM protein, Ajuba, which interacts with the amino terminus of GLT-1, the most abundant plasma membrane glutamate transporter in the brain. Ajuba has a cytoplasmic location when expressed alone in COS cells, but translocates to colocalize with GLT-1 at the plasma membrane when GLT-1 is coexpressed. Ajuba is expressed in cerebellum, cortex, hippocampus, and retina and also in organs outside the CNS. Ajuba is found with GLT-1 in astrocytes, cerebellar Bergmann glia and retinal neurons, and antibodies to Ajuba coimmunoprecipitate GLT-1 from brain. For GLT-1 expressed in COS cells, coexpression of Ajuba did not affect the transporter's K(m) or V(max) for glutamate. Since Ajuba is known to activate MAP kinase enzymes, and its homologue Zyxin binds to cytoskeletal proteins, we propose that Ajuba is a scaffolding protein allowing GLT-1 to regulate intracellular signaling or interact with the cytoskeleton.     

Statistical classification strategy for proton magnetic resonance spectra of soft tissue sarcoma: an exploratory study with potential clinical utility

Purpose: Histological grading is currently one of the best predictors of tumor behavior and outcome in soft tissue sarcoma. However, occasionally there is significant disagreement even among expert pathologists. An alternative method that gives more reliable and non-subjective diagnostic information is needed. The potential use of proton magnetic resonance spectroscopy in combination with an appropriate statistical classification strategy was tested here in differentiating normal mesenchymal tissue from soft tissue sarcoma.Methods: Fifty-four normal and soft tissue sarcoma specimens of various histological types were obtained from 15 patients. One-dimensional proton magnetic resonance spectra were acquired at 360 MHz. Spectral data were analyzed by using both the conventional peak area ratios and a specific statistical classification strategy.Results: The statistical classification strategy gave much better results than the conventional analysis. The overall classification accuracy (based on the histopathology of the MRS specimens) in differentiating normal mesenchymal from soft tissue sarcoma was 93%, with a sensitivity of 100% and specificity of 88%.The results in the test set were 83, 92 and 76%, respectively. Our optimal region selection algorithm identified six spectral regions with discriminating potential, including those assigned to choline, creatine, glutamine, glutamic acid and lipid.Conclusion: Proton magnetic resonance spectroscopy combined with a statistical classification strategy gave good results in differentiating normal mesenchymal tissue from soft tissue sarcoma specimens ex vivo. Such an approach may also differentiate benign tumors from malignant ones and this will be explored in future studies.     

Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors

Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower retention in the spleen and blood. Although overall tumor uptake was not affected by charge in the biodistribution studies, intravital microscopy showed that increasing the charge content from 10 to 50 mol % doubled the accumulation of liposomes in tumor vessels, suggesting a change in intratumor distribution; no significant effect of charge on interstitial accumulation could be detected, possibly attributable to spatial heterogeneity. Increased vascular accumulation of cationic liposomes was similar in two different tumor types and sites. Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery.     

Cystic acoustic neuromas

Predominantly cystic acoustic neuromas are rare and they usually present with clinical and radiological features different from their more common solid counterparts. Two cases of cystic acoustic neuromas are reported here.     

An ex vivo study exploring the diagnostic potential of 1H magnetic resonance spectroscopy in squamous cell carcinoma of the head and neck region

BACKGROUND: Definitive diagnosis of head and neck cancer is generally made by histopathologic evaluation. Management and prognosis largely depend on accurate and timely diagnosis. We have explored the use of (1)H magnetic resonance spectroscopy in search of a better or complementary diagnostic technique. METHODS: Tumor and adjacent normal tissue specimens (n = 135) from untreated head and neck cancer patients (n = 40) were obtained and subjected to spectroscopic evaluation followed by histopathologic analysis. Data were partitioned into training and test sets and subjected to multivariate analysis. RESULTS: The resonances from taurine, choline, glutamic acid, lactic acid, and lipid were found to have diagnostic potential by our optimal region selection algorithm. Multivariate analysis of the spectral data differentiated between normal and malignant tissues, with an overall accuracy of 92.6% (training set, 97.3%; test set, 87.3%), an overall sensitivity of 93% (test set, 90%), and an overall specificity of 92% (test set, 82.6%). CONCLUSIONS: (1)H magnetic resonance spectroscopy combined with multivariate methods of analysis can distinguish between normal and malignant squamous cell tissue, and this may lead to the development of an objective and noninvasive diagnostic procedure.