Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar.

We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus.     

Ipsilesional line bisection bias in patients with chronic parietal lesions

The current study investigated whether an ipsilesional bias in line bisection, a conventional measure for diagnosing hemispatial neglect, persists even in the absence of this syndrome in patients with chronic lesions restricted to posterior association cortex or dorsolateral prefrontal cortex. Both left and right hemisphere parietal lesions produced ipsilesional bisection errors, and to a comparable degree. Patients with lesions in frontal cortex, on the other hand, did not show a consistent bias. We conclude that chronic parietal lesions produce an ipsilesional bias in line bisection, even in the absence of other clinical signs of neglect, and that left hemisphere lesions can affect line bisection to the same degree as right hemisphere lesions.     

Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice.

PURPOSE: Recent findings indicating that many genes related to cancer development are silenced by an aberrant DNA methylation suggest that inhibitors of this process may be effective cancer therapeutics. In this study we investigated the efficacy of low-dose 5-aza-2'-deoxycitydine (DAC), a methylation inhibitor, with interleukin (IL) 12, one of the most potent cytokines with antitumor activity. Experimental Design: Mice inoculated with L1210 leukemia cells or with B16F10 melanoma cells were treated with 7 daily injections of low-dose DAC (0.2 mg/kg) and/or 7 daily doses of IL-12 (100 ng/dose). Scid/scid mice as well as monoclonal antibodies against CD4, CD8, and NK1.1 were used to investigate the mechanisms of the antitumor effects of the combination treatment. The activity of murine lymphocytes was measured with enzyme-linked immunospot and (51)Cr release assays. RESULTS: Treatment with DAC or IL-12 given alone produced moderate antitumor effects. In both tumor models combined treatment resulted in potentiated antitumor effects and produced 70% long-term survivors among mice inoculated with L1210 cells. The antitumor efficacy of combined treatment was abrogated in scid/scid mice, and after depletion of CD4(+) and CD8(+) T cells. Mice inoculated with B16F10 melanoma cells had significantly delayed tumor growth after combined treatment with DAC and IL-12. Strong antitumor effect correlated with a significant activation of lymph node-derived CD8(+) and CD4(+) cells. Transient neutropenia was observed in mice under treatment of DAC alone, but remarkably this effect was not potentiated by IL-12. CONCLUSIONS: This study provides the first evidence that antitumor effects of DAC can be strongly potentiated by IL-12 and could be beneficial in an effective low-dose-based antitumor therapy.     

Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. EXPERIMENTAL DESIGN: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[(11)C]methyl-L-cysteine ([(11)C]DCMC K(i), 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-L-tyrosine ([(125)C]DCIT K(i), 1.5 nmol/L) were synthesized using [(11)C]CH(3)I and with [(125)I]NaI/Iodogen, respectively.RESULTS: At 30 minutes postinjection, [(11)C]DCMC and [(125)I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [(11)C]DCMC or [(125)I]DCIT. CONCLUSION: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.     

The Potential of Antiseizure Drugs and Agents that Act on Novel Molecular Targets as Antiepileptogenic Treatments

A major goal of contemporary epilepsy research is the identification of therapies to prevent the development of recurrent seizures in individuals at risk, including those with brain injuries, infections, or neoplasms; status epilepticus; cortical dysplasias; or genetic epilepsy susceptibility. In this review we consider the evidence largely from preclinical models for the antiepileptogenic activity of a diverse range of potential therapies, including some marketed antiseizure drugs, as well as agents that act by immune and inflammatory mechanisms; reduction of oxidative stress; activation of the mammalian target of rapamycin or peroxisome proliferator-activated receptors γ pathways; effects on factors related to thrombolysis, hematopoesis, and angiogenesis; inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reducatase; brain-derived neurotrophic factor signaling; and blockade of α2 adrenergic and cannabinoid receptors. Antiepileptogenesis refers to a therapy of which the beneficial action is to reduce seizure frequency or severity outlasting the treatment period. To date, clinical trials have failed to demonstrate that antiseizure drugs have such disease-modifying activity. However, studies in animal models with levetiracetam and ethosuximide are encouraging, and clinical trials with these agents are warranted. Other promising strategies are inhibition of interleukin 1β signaling by drugs such as VX-765; modulation of sphingosine 1-phosphate signaling by drugs such as fingolimod; activation of the mammalian target of rapamycin by drugs such as rapamycin; the hormone erythropoietin; and, paradoxically, drugs such as the α2 adrenergic receptor antagonist atipamezole and the CB1 cannabinoid antagonist SR141716A (rimonabant) with proexcitatory activity. These approaches could lead to a new paradigm in epilepsy drug therapy where treatment for a limited period prevents the occurrence of spontaneous seizures, thus avoiding lifelong commitment to symptomatic treatment.     

Multifocal osteoma of external auditory canal in a child. A case report

Osteomas of external auditory canal are most often unilateral, solitary, pedunculated hard tumors located on the anterior and superior wall of the structure in its distal part. They have to be distinguished from exostoses of external auditory meatus. Osteomas of external auditory canal are very rare and apart from isolated cases are not described in children population. The case presented in the paper shows the possibility of a presence of unilateral multifocal osteoma of an external auditory canal in a child, which is not described in the literature concerning the topic.     

Melatonin-induced modulation of glucose metabolism in primary cultures of rabbit kidney-cortex tubules

The effect of melatonin on glucose metabolism in the presence and absence of insulin has been investigated in the primary cultures of renal tubules grown in a defined medium. In the absence of glucose in the medium containing 5 microg/mL of insulin and 2 mm alanine + 5 mm glycerol + 0.5 mm octanoate, 100 nm melatonin stimulated both glucose and lactate synthesis, while in the medium devoid of insulin melatonin action was negligible. Melatonin-induced increase in glucose and lactate synthesis was accompanied by an enhancement of alanine and glycerol consumption. In view of measurements of [U-14C]L-alanine and [U-14C]L-glycerol incorporation into glucose, it is likely that melatonin increased alanine utilization for glucose production, while accelerated lactate synthesis was because of an enhanced glycerol consumption. As (i) 10 nm luzindole attenuated the stimulatory action of melatonin on glucose formation and (ii) the indole induced a decrease in intracellular cAMP level, it seems likely that in renal tubules melatonin binds to ML1 membrane receptor subtype. In view of a decline of intracellular fructose-1,6-bisphosphate content accompanied by a significant rise in hexose-6-phosphate and glucose levels, melatonin might result in an acceleration of flux through fructose-1,6-bisphosphatase probably because of an increase in the active, dephosphorylated form of this enzyme. Thus, the administration of melatonin in combination with insulin might be beneficial for diabetic therapy because of protection against hypoglycemia.