Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients.

Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration.     

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.     

Reversible Verbal and Visual Memory Deficits after Left Retrosplenial Infarction

The retrosplenial cortex is a cytoarchitecturally distinct brain structure located in the posterior cingulate gyrus and bordering the splenium, precuneus, and calcarine fissure. Functional imaging suggests that the retrosplenium is involved in memory, visuospatial processing, proprioception, and emotion.We report on a patient who developed reversible verbal and visual memory deficits following a stroke. Neuropsychological testing revealed both anterograde and retrograde memory deficits in verbal and visual modalities. Brain diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) demonstrated an acute infarction of the left retrosplenium.     

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Purpose  

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.     

Experimental transplantation gliomas in the adult cat brain

Summary In adult cats experimental brain tumours were produced by stereotactical xenotransplantation of the rat glioma clone F 98 into the internal capsule of the left hemisphere. Two to four weeks after transplantation tumours and peritumoural oedema were investigated by magnetic resonance imaging (MRI), electrophysiological recording and analysis of tissue content of water, electrolytes and extravasated serum proteins.Spherical tumours with a diameter of about 10 mm developed at the injection site and were surrounded by massive white matter oedema. Water content in peritumoural white matter increased from 2.63 ± 0.17 to 3.65 ± 0.19 ml/g d.w. (means ± SD), sodium from 187±11 to 351±55 eq/g d.w. and calcium from 7.4±1.1 to 13.3 ± 1.3 ± 1.3 eq/g d.w. Potassium and magnesium did not change. Oedema development was associated with the extravasation of 18.0 ± 16.8mg/g d.w. albumin and 15.8 ± 12.2 mg/g d.w. immunoglobulin. The calculated electrolyte content of oedema fluid approximated that of plasma but the serum protein content was about 40% lower. The ratio of low (albumin) to high (immunoglobulin) molecular weight proteins was the same in blood and oedema fluid. It is, therefore, concluded that peritumoural oedema consist of two components,a whole plasma extravasate and a protein-free ultra-filtrate.Peritumoural oedema could be clearly detected by MRI but differentiation between tumour and oedema was only possible after contrast enhancement with gadolinium-DTPA. The ratios of the intensities of the MR signal correlated linearly with the water content within white matter. MRI, in consequence, allows quantification of oedema provided a reference area with normal water content is present.     

Association of MICA polymorphism with HLA-B51 and disease severity in Korean patients with Behcet's disease

The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many ethnic group. However, it has not yet been clarified whether the HLA-B51 gene itself is the pathogenic gene related to BD or whether it is some other gene in linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC) polymorphism in transmembrane region of the MHC class I chain-related A (MICA) gene was identified. To investigate the association of MICA with BD, we studied the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in relation to the presence of HLA-B51 and clinical manifestations. The triplet repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6 allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were significantly increased in the Korean patients with BD. A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with BD and control subjects. Stratification analysis showed that MICA*A6 homozygosity was strongly associated with BD in the HLA-B51-negative population, and HLA-B51 was also associated with MICA*A6-negative population. In conclusion, MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD, and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the HLA-B5-negative     

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.