Hirose Y

Induction of Manganese Superoxide Dismutase by Cytokines and Lipopolysaccharide in Cultured Mouse Astrocytes

Abstract: To determine whether cytokines or lipopolysaccharide (LPS) are involved in the induction of superoxide dismutase (SOD) in the nervous system, we examined the effects of these substances on the levels of SOD in cultured mouse astrocytes. Treatment of astrocytes with 102 to 104 U/ml tumor necrosis factor‐α for 3 days increased the levels of Mn SOD in a dose‐ and time‐dependent manner to as much as six times the level under nontreated conditions. Treatment with 1.0 µg/ml LPS for 3 days elicited a fourfold increase in levels of Mn SOD, and the effect of LPS was also dose dependent. Furthermore, Mn SOD in astrocytes was induced by a 3‐day exposure to interleukin‐1α at concentrations of 102 or 103 U/ml. However, these stimuli had no effect on levels of copper‐zinc SOD (Cu/Zn SOD) in astrocytes. By contrast, interferon‐γ did not change the levels of either Mn or Cu/Zn SOD in the cells. The results indicate that the selective induction of Mn SOD by cytokines and LPS, which has been observed in nonnervous tissues, may also occur in nervous tissues. The induction of Mn SOD may represent a mechanism for protection of cells from oxidative stress.

Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.

Elevated serum levels of manganese superoxide dismutase in polymyositis and dermatomyositis

we studied serum concentrations of manganese superoxide dismutase (Mn SOD) and copper-zinc superoxide dismutase (Cu/Zn SOD) in 22 patients with polymyositis and dermatomyositis (PM/DM), 87 patients with four types of muscular dystrophy, 20 patients with amyotrophic lateral sclerosis, and 15 patients with collagen vascular diseases (CVD). Serum levels of Mn SOD were increased only in the patients with PM/DM and CVD, and the elevation was more prominent in those with PW/DM. Levels of Cu/Zn SOD were slightly elevated in some patients with PM/DM and Duchenne muscular dystrophy. In patients with PM/DM, the change in Mn SOD levels corresponded to disease activity as closely as or more closely than those of creatine kinase. The results indicate that serum Mn SOD may be a useful clinical marker for PM/DM.

Two autopsy cases of multiple cerebral tuberculomas

Two cases of multiple cerebral tuberculomas are described. A 59‐year‐old female had liver cirrhosis and was suspected of having metastatic tumors in the brain. A 65‐year‐old female had chronic renal failure and was diagnosed with miliary tuberculosis and treated with antituberculous drugs. In both cases, consciousness became disturbed gradually. Both patients were diagnosed with multiple cerebral tuberculomas after death. Histologically, both cases showed cerebral granulomas comprising epithelioid cells mixed with reactive astrocytes, and fibrous gliosis surrounding a core of caseous necrosis. These lesions were readily detected by Holzer staining. Some blood vessels around the granulomas showed vasculitis with lymphocyte infiltration in the walls and obliteration of the lumina by epithelioid cell proliferation. In this report, the unique histological features of the multiple cerebral tuberculoma are described and it is suggested that the obliterative vasculitis around them may have caused the disturbed consciousness.

Thrombolytic therapy with transbrachial superselective catheterization for acute occlusive cerebrovascular disease. A case report.

失語, 右片麻痺を呈し, 脳血管造影で左中大脳動脈の起始部でのアテローム血栓性脳梗塞と診断された69歳の男性に対し, 新しく共同開発したカテーテルにより上腕動脈から, 超選択的カテーテル挿入による血栓溶解療法を行った.ウロキナーゼ48万単位により再開通が認められ, 神経徴候は著明に改善した。経上腕動脈アプローチでも, マイクロカテーテルによる頭蓋内血管の超選択的血栓溶解療法は十分に可能であることが示唆された.