Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes

BACKGROUND: Taurine, a potent antioxidant, has been reported to improve streptozotocin-induced diabetes mellitus, in which the development of diabetes results from an attack by oxygen free radicals on pancreatic beta cells. However, taurine also increases the excretion of cholesterol via conversion to bile acid and would be expected to improve insulin resistance. OBJECTIVE: The effects of taurine on insulin sensitivity were examined in a model rat of insulin resistance and type 2 diabetes-the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. DESIGN: Male OLETF rats were divided into 2 groups at the age of 16 wk: a taurine-supplemented group and an unsupplemented group. As a nondiabetic control, Long-Evans-Tokushima-Otsuka rats were used. An oral-glucose-tolerance test and hyperinsulinemic euglycemic clamp were performed at the ages of 23 and 25 wk. RESULTS: The OLETF rats had hyperglycemia and insulin resistance and they had a greater accumulation of abdominal fat than did control rats. Abdominal fat accumulation, hyperglycemia, and insulin resistance were significantly lower in the taurine-supplemented group than in the unsupplemented group. Serum and liver concentrations of triacylglycerol and cholesterol were significantly higher in the OLETF rats than in the control rats and were significantly lower in the taurine-supplemented group than in the unsupplemented group, presumably because of the increased secretion of cholesterol into bile acid. Taurine-supplemented rats also showed higher nitric oxide secretion, evidenced by increased urinary excretion of nitrite. CONCLUSION: Taurine effectively improves metabolism in OLETF rats by decreasing serum cholesterol and triacylglycerol, presumably via increased secretion of cholesterol into bile acid and decreased production of cholesterol because of increased nitric oxide production.     

Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA

To elucidate the sites of and mechanisms of analgesic effect of centrally injected calcitonin, we examined expression of calcitonin receptor mRNA in the mouse brain by in situ hybridization techniques. Calcitonin receptor mRNA was expressed in various brain regions, including the preoptic area, dorsomedial hypothalamic nucleus, lateral hypothalamic area, periaqueductal gray, dorsal raphe nucleus, locus coeruleus, lateral parabrachial nucleus, gigantocellular reticular nucleus alpha part, lateral paragigantocellular nucleus, raphe magnus nucleus and solitary tract nucleus, which are known to play important roles in pain modulation. In addition, a double in situ hybridization technique demonstrated the intense expression of calcitonin receptor mRNA on serotonergic neurons in some raphe nuclei and the lateral paragigantocellular nucleus, suggesting the involvement of central serotonergic pathways in analgesic effect of calcitonin.     

Serial changes in N-isopropyl-p[125I]-iodoamphetamine in mouse lung observed with a confocal laser scanning microscope

Serial changes in N-isopropyl-p[125I]-iodoamphetamine (125I-IMP) in mouse lungs were observed with a confocal laser scanning microscope. Male mice were intravenously injected with 125I-IMP and subjected to autoradiographic procedures 20 minutes, and 3 and 24 hours after injection. Differential interference contrast (DIC) images and confocal images were obtained with a confocal laser scanning microscope, and superimposed images were evaluated. Large numbers of silver grains were observed in the interstitium, bronchioles, and alveolar sacs 20 minutes after the injection, and lamellar distribution of the grains was observed on the ciliary surface. The numbers of silver grains in the interstitium and bronchioles had decreased 3 hours after the injection of 125I-IMP, but the numbers of silver grains in the alveolar spaces had not. Although small numbers of silver grains remained in both the bronchioles and alveolar sacs 24 hours after the injection, most of them had washed out. Confocal laser scanning microscopy is considered to be a useful procedure for studying the distribution of radioisotopes by microautoradiography, because it allows clear autoradiographs to be obtained in which tissues and silver grains are perfectly matched and all silver grains are in focus.     

Effects of Inhalation or Incubation of Oxitropium Bromide on Diaphragm Muscle Contractility in Mice

BackgroundAlthough oxitropium bromide is used clinically as an anticholinergic drug (i.e., parasympathetic antagonist) to relax airway smooth muscle, we examined whether it has or does not have any effects on diaphragm muscle.MethodsThree treatment sets, an oxitropium bromide inhalation only group, an oxitropium bromide inhalation plus endotoxin injection group (in vivo) and an oxitropium bromide incubation group (in vitro) were studied as to diaphragm muscle contractile properties.ResultsOxitropium bromide inhalation shifted force-frequency curves upward at 2 h after inhalation (p < 0.05) and inhibited the decrease of force-frequency curves due to endotoxin injection in vivo. Incubation with oxitropium bromide of untreated diaphragm muscle and diaphragm muscle injected with endotoxin did not increase the force-frequency curves dose-dependently in vitro; however, it caused both types of muscle to be fatigue resistant.ConclusionsWe speculate that the increment of muscle contractility with the inhalation of oxitropium bromide was induced by the antagonization of musucarinic acetylcholine receptors (mAChR). In addition, the changes of fatigue resistance provoked by oxitropium bromide, which also is speculated to antagonize mAChR, may be beneficial in the treatment of patients with COPD.     

Cutaneous lesions of Kikuchi's disease: Evolution of histopathological findings

We report a 38‐year‐old male patient who presented with cutaneous lesions mimicking widespread discoid lupus erythematosus with high‐grade fever, arthralgia and lymphadenopathy. Additional lymph node and skin biopsies, however, revealed karyorrhectic debris without neutrophils and numerous CD68‐positive cells, a characteristic finding of Kikuchi's disease (KD). Comparing skin biopsies on different occasions, we could see different forms of histopathology. The histopathology of skin lesions of KD may vary during the clinical course, which may reflect the stage of the disease.     

Multiple cerebral infarcts with a few vasculitic lesions in the chronic stage of cerebral amyloid angiopathy‐related inflammation

We report a 75‐year‐old man with a 3.5‐year history of cerebral amyloid angiopathy (CAA)‐related inflammation. His initial symptom was headache and sensory aphasia appeared 1 month later. Brain MRI revealed features compatible with meningoencephalitis involving the right frontal, parietal and temporooccipital lobes. A brain biopsy sample from the right parietal lobe showed thickening of the leptomeninges, and granulomatous vasculitis with multinucleated giant cells and vascular Aβ deposits. No vascular lesions were evident by cerebral angiography. Serological examination revealed an elevated level of proteinase 3 anti‐neutrophil cytoplasmic autoantibodies (PR3‐ANCA). The patient was treated with corticosteroids, but this was only partially and temporarily effective. Autopsy revealed marked leptomeningeal thickening with inflammatory cell infiltrates and hemosiderin deposits, many superficial predominantly small infarcts at various stages in the cerebral cortex and only a few cerebral active vasculitic lesions. Immunohistochemically, CAA showing widespread Aβ‐positive blood vessels with double‐barrel formations was demonstrated. In conclusion, we consider that, although the association of PR3‐ANCA with the pathogenesis of Aβ‐associated vasculitis remained unclear, the present case represents a rare example of CAA‐related inflammation at the chronic stage.