A clinico-pathological study of so-called "acute multiple sclerosis" mimicking a brain tumor on the MRI findings]

We are reporting an autopsy case of so-called "acute multiple sclerosis" that was difficult to differentiate from a brain tumor on MRI findings. This case was a 69-year-old man, whose initial symptoms consisted of headache and unsteadiness in walking. Neurological findings included mild ataxia of the left upper extremity and positive Romberg sign. T 2-weighted MRI showed high intensity areas in the posterior limb of the right internal capsule and white matter near the posterior horn of the right lateral ventricle. Although the headache improved, the unsteadiness was exacerbated and the patient became unable to keep standing. Psychiatric symptoms and left hemiparesis were added to the clinical picture. The following MRI proved expansion of the previous lesions and the diffusely enhanced lesion spreading into the contralateral side through the corpus callosum. Stereotaxic biopsy showed the perivascular accumulation of small lymphocytes and a large number of bizarre astrocytes. Primary brain malignant lymphoma was diagnosed and radiation therapy was carried out. However, he developed perforation of the intestinal tract and died. Autopsy findings revealed scattered and disseminated small lesions in the cerebral white matter and the corpus callosum. There were a large number of lipid-laden macrophages, no stainable myelin and preserved axis cylinders in those lesions. Thus, those were interpreted as demyelinting lesions. They were scattered and multiple. This case was radiologically characterised by the diffusely enhanced, expanding butterfly-shaped lesion in bilateral cerebral hemisphere through the corpus callosum, and pathologically proven to be acute demyelination associated with severe perivascular infiltration of inflammatory cells. Multiple sclerosis may mimic neoplastic processes as trans-callosal hyperplastic neuroimage on neuroimaging like the present case.     

Plasminogen activator inhibitor 1 in central serous chorioretinopathy

PURPOSE: To describe the plasma level of plasminogen activator inhibitor 1, the major antifibrinolytic agent, in eyes with central serous chorioretinopathy, in which choroidal thrombosis is suspected as the underlying condition based on the findings of choroidal hyperpermeability in indocyanine green angiograms. METHODS: Plasminogen activator inhibitor 1 concentrations in the plasma of 17 patients with central serous chorioretinopathy were measured by enzyme-linked immunosorbent assay and compared with those in 12 age-matched normal volunteers. RESULTS: The plasma levels of plasminogen activator inhibitor 1 in patients with central serous chorioretinopathy (range, 25 to 439 ng/ml; median, 87 ng/ml) were significantly increased compared with those in normal volunteers (range, 7 to 84 ng/ml; median, 36 ng/ml) (P = .0013, Mann-Whitney U test). CONCLUSION: Increased plasminogen activator inhibitor 1 concentrations in patients with central serous chorioretinopathy support the hypothesis that the choroidal hyperpermeability disclosed by indocyanine green angiography is caused from impaired fibrinolysis and the resulting thrombotic occlusion in the choroidal veins.     

Altered expression of amyloid precursors proteins after traumatic brain injury in rats: in situ hybridization and immunohistochemical study

The expression of alternatively spliced mRNAs for amyloid precursor protein (APP) isoforms and their translation products were examined in the rat cerebral cortex 1, 3, 6, and 12 h and 1, 3, and 7 days (n = 4-5 in each group) after fluid-percussion brain injury. In situ hybridization studies demonstrated that the expression of APP695 mRNA decreased in and around the damaged area of the cerebral cortex exposed to fluid-percussion injury 1 h after the insult. On the other hand, APP751/770 mRNAs were increased in the regions surrounding the damaged cortical areas 1 day after the injury. An increase of immunoreactive APP was detected in the regions around the damaged cortical areas 3 h after traumatic injury and maintained for the following 3 days. The APP immunoreactivity in the damaged cortices declined to the level of sham-operated animals by post-experimental day 7. Using an anti-amyloid beta (Abeta) protein (17-24) antibody, no deposits of immunoreactive Abeta (17-24) were observed in any of the samples examined in these experiments. These results suggest that the induction of Kunitz-type protease inhibitor (KPI) domain-containing APP mRNAs and the increased accumulation of APP are involved in the physiological and neuropathological responses of brains under various neurodegenerative conditions, including head trauma.     

In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active metabolite of irinotecan) in human carcinoma cell lines

Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects of drug combinations at the IC₈₀ level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic (subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist in determining the optimal schedule for this combination in clinical use. Received: 25 February 1997 / Accepted: 6 November 1997     

刺人参甙Q和R的分离与结构鉴定

从刺人参叶中分离并鉴定了2种新甙,丝石竹皂甙元-3-O-β-D呲喃葡萄糖基-28-O-α-L-呲喃鼠李糖基(1→4)-β-D-呲喃葡萄糖基(1→6)-β-D-呲喃葡萄糖甙和3β-羟基羽扇豆-20(29)-烯-23-醛-28-酸-3-O-β-D-呲喃葡萄糖基-28-O-α-L-呲喃鼠李糖基(1→4)-β-D-呲喃葡萄糖基(1→6)-β-D-呲喃葡萄糖甙。     

Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling

To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.     

Quercetin-induced PC12 cell death accompanied by caspase-mediated DNA fragmentation

Flavonoids have been reported to be potent antioxidants and beneficial in oxidative stress related diseases. Quercetin, a major flavonoid in food, deserves much attention because of its antioxidative activity. However, the actions of flavonoids including quercetin are complex and paradoxical. Quercetin caused apoptosis and/or cell death in various cells including cancer cells and normal cells. In this study, we investigated the effects of quercetin with or without hydrogen peroxide (H2O2) on cell death of PC12 cells, a neuronal cell line. We showed that quercetin at 10-30 microM alone caused cell death accompanied by caspase-mediated DNA fragmentation in undifferentiated PC12 cells. Quercetin did not inhibit and rather enhanced 0.1 mM H2O2-induced cell death. The toxic effect of quercetin was not inhibited by antioxidants such as N-acetylcysteine and GSH, although H2O2-induced cell death was inhibited by the antioxidants. Quercetin-induced cell death was reduced by 2 h treatment with nerve growth factor and serum. In addition, quercetin caused cell death in differentiated PC12 cells that were cultured with nerve growth factor for 6 d. Genistein, a soy isoflavone that has the pro-apoptotic activity, also caused cell death with DNA fragmentation. Further evaluation of the potential of dietary flavonoids as neuroprotective reagents is needed.