Liquid Structure and Dynamics of Aqueous Isopropanol over gamma-Alumina

The liquid structures of thin films of aqueous solutions of 0, 7, 19, 50, and 100 mol % isopropanol above O/Al-terminated gamma-alumina surfaces have been investigated by means of classical molecular dynamics simulations. The structuring effect of the oxide oil the liquid mixtures is strong and heavily dependent on the local structure of the oxide. Two distinct re-ions are found oil the oxide Surface characterized by the degree of coordination of Al atoms. Above octahedral Al atoms, water and isopropanol molecules adsorb via the oxygen atoms to maximize the electrostatic interaction, whereas above tetrahedral Al sites the solvent molecules adsorb via hydrogen atoms with the oxygen atoms away front the surface. More mobility is found in the second layer compared with the first; however, its structure is still influenced significantly by the orientation of molecules in the first adsorbed layer. Qualitatively, the displacement of water from the surface by the adsorption of isopropanol occurs with 2.6 Water molecules lost for every alcohol molecule present based on the effective surface areas of the two species calculated from the pure simulations.

Electron shell contributions to gamma-ray spectra of positron annihilation in noble gases

Gamma-ray positron annihilation spectra of the noble gases are simulated using computational chemistry tools for the bound electron wavefunctions and plane-wave approximation for the low-energy positron. The present annihilation line shapes, i.e. the full width at half maximum, Delta epsilon, of the gamma-ray annihilation spectra for He and Ar (valence) agree well with available independent atomic calculations using a different algorithm. For other noble gases they achieve moderate agreement with the experimental measurements. It is found that the contributions of various atomic electron shells to the spectra depend significantly on their principal quantum number n and orbital angular momentum quantum number l. The present study further reveals that the outermost ns electrons of the noble gases exhibit spectral line shapes in close agreement with those measured, indicating (as expected) that the measurements are not due to a simple sum over the momentum densities for all atomic electrons. The robust nature of the present approach makes it possible for us to proceed to more complex molecular systems using the tools of modern computational chemistry.

Many-body theory of gamma spectra from positron-atom annihilation

A many-body theory approach to the calculation of gamma spectra of positron annihilation on many-electron atoms is developed. We evaluate the first-order correlation correction to the annihilation vertex and perform numerical calculations for the noble gas atoms. Extrapolation with respect to the maximal orbital momentum of the intermediate electron and positron states is used to achieve convergence. The inclusion of correlation corrections improves agreement with experimental gamma spectra.

Stereotactic radiosurgery for intractable cluster headache: an initial report from the North American Gamma Knife Consortium.

Abstract Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26-83 years). The median duration of pain before GKS was 10 years (range 1.3-40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I-IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

Role of Delta Np63 gamma in Epithelial to Mesenchymal Transition

Although members of the p63 family of transcription factors are known for their role in the development and differentiation of epithelial surfaces, their function in cancer is less clear. Here, we show that depletion of the Delta Np63 alpha and beta isoforms, leaving only Delta Np63 gamma, results in epithelial to mesenchymal transition (EMT) in the normal breast cell line MCF10A. EMT can be rescued by the expression of the Delta Np63 alpha isoform. We also show that Delta Np63 gamma expressed in a background where all the other Delta Np63 are knocked down causes EMT with an increase in TGF beta-1, -2, and -3 and downstream effectors Smads2/3/4. In addition, a p63 binding site in intron 1 of TGF beta was identified. Inhibition of the TGF beta response with a specific inhibitor results in reversion of EMT in Delta Np63 alpha- and beta-depleted cells. In summary, we show that p63 is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers.

Repression of NHE1 Expression by PPAR gamma Activation Is a Potential New Approach for Specific Inhibition of the Growth of Tumor Cells In vitro and In vivo

Ligand-induced activation of peroxisome proliferator-activated receptor gamma (PPAIR gamma) inhibits proliferation in cancer cells in vitro and in vivo; however, the downstream targets remain undefined. We report the identification of a peroxisome proliferator response element in the promoter region of the Na+/ H transporter gene NHE1, the overexpression of which has been associated with carcinogenesis. Exposure of breast cancer cells expressing high levels of PPAR gamma to its natural and synthetic agonists resulted in downregulation of NHE1 transcription as well as protein expression. Furthermore, the inhibitory effect of activated PPAR gamma on tumor colony-forming ability was abrogated on overexpression of NHE1, whereas small interfering RNA-mediated gene silencing of NHE1 significantly increased the sensitivity of cancer cells to growth-inhibitory stimuli. Finally, histopathologic analysis of breast cancer biopsies obtained from patients with type II diabetes treated with the synthetic agonist rosiglitazone showed significant repression of NHE1 in the tumor tissue. These data provide evidence for tumor-selective downregulation of NHE1 by activated PPAR gamma in vitro and in pathologic specimens from breast cancer patients and could have potential implications for the judicious use of low doses of PPAR gamma ligands in combination chemotherapy regimens for an effective therapeutic response. [Cancer Res 2009;69(22):8636-44]

Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. Clinical article

Object
Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes.

Methods
The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26–95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy.

Results
Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I–IIIb). Significant pain relief (BNI Scores I–IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I–IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of = 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3–144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and = 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years).

Conclusions
Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.

Gamma Knife Radiosurgery as a Therapeutic Strategy for Intracranial Sarcomatous Metastases

Purpose: To determine the indication and outcomes for Gamma Knife stereotactic radiosurgery (GKSRS) in the care of patients with intracranial sarcomatous metastases. Methods and Materials: Data from 21 patients who underwent radiosurgery for 60 sarcomatous intracranial metastases (54 parenchymal and 6 dural-based) were studied. Nine patients had radiosurgery for solitary tumors and 12 for multiple tumors. The primary pathology was metastatic leiomyosarcoma (4 patients), osteosarcoma (3 patients), soft-tissue sarcoma (5 patients), chondrosarcoma (2 patients), alveolar soft part sarcoma (2 patients), and rhabdomyosarcoma, Ewing's sarcoma, liposarcoma, neurofibrosarcoma, and synovial sarcoma (1 patient each). Twenty patients received multimodality management for their primary tumor, and 1 patient had no evidence of systemic disease. The mean tumor volume was 6.2 cm 3 (range, 0.07-40.9 cm 3), and a median margin dose of 16 Gy was administered. Three patients had progressive intracranial disease despite fractionated whole-brain radiotherapy before SRS. Results: A local tumor control rate of 88% was achieved (including patients receiving boost, up-front, and salvage SRS). New remote brain metastases developed in 7 patients (33%). The median survival after diagnosis of intracranial metastasis was 16 months, and the 1-year survival rate was 61%. Conclusions: Gamma Knife radiosurgery was a well-tolerated and initially effective therapy in the management of patients with sarcomatous intracranial metastases. However, many patients, including those who also received fractionated whole-brain radiotherapy, developed progressive new brain disease. © 2010 Elsevier Inc. All rights reserved.

Glycoprotein VI/Fc receptor gamma chain-independent tyrosine phosphorylation and activation of murine platelets by collagen

We have investigated the ability of collagen to induce signalling and functional responses in suspensions of murine platelets deficient in the FcRgamma (Fc receptor gamma) chain, which lack the collagen receptor GPVI (glycoprotein VI). In the absence of the FcRgamma chain, collagen induced a unique pattern of tyrosine phosphorylation which was potentiated by the thromboxane analogue U46619. Immunoprecipitation studies indicated that neither collagen alone nor the combination of collagen plus U46619 induced phosphorylation of the GPVI-regulated proteins Syk and SLP76 (Src homology 2-containing leucocyte protein of 76 kDa). A low level of tyrosine phosphorylation of phospholipase Cgamma2 was observed, which was increased in the presence of U46619, although the degree of phosphorylation remained well below that observed in wild-type platelets (similar to 10%). By contrast, collagen-induced phosphorylation of the adapter ADAP (adhesion- and degranulation-promoting adapter protein) was substantially potentiated by U46619 to levels equivalent to those observed in wild-type platelets. Collagen plus U46619 also induced significant phosphorylation of FAK (focal adhesion kinase). The functional significance of collagen-induced non-GPVI signals was highlighted by the ability of U46619 and collagen to induce the secretion of ATP in FcRgamma chain-deficient platelets, even though neither agonist was effective alone. Protein tyrosine phosphorylation and the release of ATP were abolished by the anti(alpha2 integrin) antibodies Ha1/29 and HMalpha2, but not by blockade of alphaIIbbeta3. These results illustrate a novel mechanism of platelet activation by collagen which is independent of the GPVI-FcRgamma chain complex, and is facilitated by binding of collagen to integrin alpha2beta1.