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Mitsugu Nakamura, Norihiko Tamaki, Tetsuro Kawaguchi and Shigekiyo Fujita

A transvenous embolization technique that spares normal cerebral venous drainage is described. Of 26 dural carotid-cavernous fistulas treated by the authors, in three cases the affected cavernous sinus was supplied by not only the shunt flow but also the sylvian venous drainage. Two patients presented with an abducent nerve palsy and one with an oculomotor nerve palsy in whom selective transvenous embolization of the fistulous portions of the affected cavernous sinus was achieved while preserving of the sylvian venous outflow. Posttransvenous embolization angiograms showed complete occlusion of the fistula in one patient and only small residual shunts in the other two; one underwent subsequent transarterial embolization, whereas the other was followed without additional treatment. The patients' symptoms disappeared between 1 and 2 months posttreatment. Follow-up angiograms revealed that the remnant shunt had disappeared and that the sylvian venous pathway had been preserved. The authors conclude that although the condition is uncommon it is important to recognize that a dural carotid-cavernous sinus fistula, which receives significant sylvian venous outflow, can be treated successfully by selective transvenous embolization of the fistulous compartments in an affected sinus.

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Kazuyoshi Korosue, Norihiko Tamaki, Satoshi Matsumoto and Yoshiyuki Ohi

✓ The authors report a rare case of intracranial granuloma as a complication of subdural-peritoneal shunting for the treatment of subdural effusion. The necessity of the removal of the entire shunt system as soon as the subdural effusion has cleared is emphasized.

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Norihiko Tamaki, Takayuki Shirakuni, Kazumasa Ehara and Satoshi Matsumoto

✓ The magnetic resonance longitudinal relaxation time (T1) and transverse relaxation time (T2) of the water proton of the periventricular white and cortical gray matter were measured for 17 control patients and 21 patients with suspected normal-pressure hydrocephalus (NPH). Of the latter group, 14 showed good response to shunting (true-NPH group) and seven showed no response (false-NPH group). In the true-NPH group, both the T1 and the T2 of the periventricular white matter were significantly prolonged compared to the control values, and slowly shortened after cerebrospinal fluid (CSF) shunting. The true-NPH group showed significantly longer T1 and T2 of the white matter than did the false-NPH group. The T1 and T2 of the white matter were longer than those of the gray matter in this group, which was the reverse of the relationship observed in the control patients. In the white matter of the false-NPH group, there was a significant prolongation of T1 only; no difference was seen in the T2 compared to control values. There was no change in either T1 or T2 of this region after CSF shunting. The false-NPH group showed no significant difference in either T1 or T2 between the white and the gray matter. There was no difference in either T1 or T2 of the gray matter between the false-NPH and control groups or between preshunt and postshunt measurements in each patient group. It is suggested that a distinction between true- and false-NPH, which cannot be made from the radiographic appearance alone, may be possible from measurement of relaxation times. The mechanism of varied relaxation behavior between two entities may be explained by a difference in properties of the biological water and its environment.

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Takashi Kokunai, Norihiko Tamaki and Satoshi Matsumoto

✓ A human monoclonal antibody (CLN-IgG) was produced from a human-human hybridoma derived from lymphocytes of a patient with cervical carcinoma. The reactivities of this antibody with various human glioma tissues and cultured glioma cells and the characterization of the antigen recognized by CLN-IgG on malignant glioma cells were analyzed and reported. CLN-IgG reacted with various human glioma cells and glioma tissues, especially glioblastoma, but did not react with normal brain tissues or fetal brain tissues. A large amount of antigen recognized by CLN-IgG was expressed on cell membranes of undifferentiated glioma cells and of glioma cells at the G2/M tumor growth phase in cycling cells. Antigen recognized by CLN-IgG was detected in only one of seven samples of cyst fluid, and was not detected in 27 serum samples or 18 samples of cerebrospinal fluid from glioma patients. CLN-IgG exhibited antibody-dependent cell cytotoxicity against U-251MG glioma cells and primary cultured cells of glioblastomas and anaplastic astrocytomas. These data suggest that the antigen recognized by CLN-IgG might be related to cell proliferation in malignant gliomas. Thus, CLN-IgG might be useful for immunotherapy or immunoimaging of malignant gliomas.

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ACNU-resistant mutants of 9L rat glioma cell line

Isolation and preliminary characterization of these subclones

Takashi Kokunai, Norihiko Tamaki and Satoshi Matsumoto

✓ Three ACNU-resistant subclones were isolated and characterized from a wild-typed 9L rat glioma cell line in culture. At an early stage after cloning, these ACNU-resistant subclones showed a high frequency of chromosomal aberrations compared with nonresistant 9L cells. These ACNU-resistant subclones revealed a cross resistance to BCNU, CCNU, methyl CCNU, nitrogen mustard, cyclophosphamide, and cis-platinum, which are alkylating agents. Further studies are necessary to clarify the mechanisms of ACNU-resistance from the aspect of repair of DNA alkylation damage.

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Kohkichi Hosoda, Norihiko Tamaki, Michio Masumura and Satoshi Matsumoto

✓ The clinical and radiological findings in a case of brain-stem encephalitis are described with special emphasis on the serial magnetic resonance imaging. This pathological condition should be differentiated from brain-stem tumors, which may present with similar symptoms.

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Dali Yin, Norihiko Tamaki and Takashi Kokunai

Object. In an attempt to understand the roles of several apoptosis-related genes in human glioma cells, the authors investigated the relationship of wild-type p53, interleukin-1β—converting enzyme (ICE), caspase-3 (CPP32), bax, and bcl-2 to the apoptotic response of three glioma cell lines after treatment with etoposide.

Methods. A human glioma cell line (U-87MG) that expresses wild-type p53, one that expresses mutant p53 (T-98G), and a T-98G derivative (T-98G/p53) that was transfected with a wild-type p53 expression vector (pCDM8-p53/neo) were used. Cell growth inhibition in response to etoposide was quantified using a modified methylthiazol tetrazolium colorimetric assay. Induction of apoptosis was evaluated using Hoechst 33258 staining and a DNA fragmentation assay. To study the expression of the apoptosis-related proteins and messenger RNAs in the three glioma cell lines, Western blotting and polymerase chain reaction were performed. A caspase assay and Western blot analysis were used to assess CPP32 and ICE protease activity. A CPP32 inhibition assay was used to determine whether a specific CPP32 inhibitor, DEVD-CHO, affects the apoptosis induced by etoposide in malignant glioma cells. Etoposide significantly inhibited the growth of U-87MG and T-98G/p53 cells in a dose-dependent manner compared with the growth of the T-98G cells. Treatment with low concentrations of etoposide resulted in the increased expression of wild-type p53; it also initiated CPP32 activity and induced apoptosis in the U-87MG cells. Apoptosis was not induced in T-98G cells at low concentrations of etoposide, although it was induced at high concentrations. Furthermore, low concentrations of etoposide also induced apoptosis in the T-98G/p53 cells by enhancing the expression of transfected wild-type p53, decreasing the expression of bcl-2, and activating CPP32 activity. However, etoposide did not alter the expression of bax and did not initiate ICE activity in these three glioma cell lines. Etoposide-induced apoptosis can be suppressed by the CPP32 inhibitor DEVD-CHO.

Conclusions. These findings indicate that wild-type p53, CPP32, and bcl-2 may mediate apoptosis induced by etoposide. Forced expression of wild-type p53 increases etoposide cytotoxicity in human glioma cells by inducing apoptosis and may have important therapeutic implications.

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Synergistic effect of perfluorochemicals on BCNU chemotherapy

Experimental study in a 9L rat brain-tumor model

Keiichi Kuwamura, Takashi Kokunai, Norihiko Tamaki and Satoshi Matsumoto

✓ In a study of the effect of adding perfluorochemicals to BCNU chemotherapy, 7 × 105 9L tumor cells were implanted in the right cerebral hemisphere of Fischer 344 rats weighing about 100 gm each. On the 7th day after implantation, rats were given BCNU or Fluosol-43 (perfluorochemical artificial blood substitute), or a combination of the two, and the therapeutic effects of these treatments were studied. Mean survival time of control animals was 15.23 days ± 2.84 days (standard deviation); in the group treated with Fluosol-43 and kept in an oxygen chamber (95% O2, 5% CO2), survivial time was 15.30 ± 2.11 days. The BCNU treatment alone and BCNU in rats kept in an oxygen chamber prolonged the mean survival time to 20.90 ± 3.80 days and 21.10 ± 2.14 days, respectively. Survival times in rats receiving BCNU plus Fluosol and breathing normal air, BCNU plus dextran-40 and breathing normal air, and BCNU plus dextran-40 in an oxygen chamber were 21.20 ± 2.63 days, 22.90 ± 1.52 days, and 22.20 ± 1.79 days, respectively. On the other hand, treatment with BCNU plus Fluosol-43 in rats kept in an oxygen chamber resulted in a significant increase of mean survival time of 32.27 ± 4.80 days (p < 0.005). From these results, it seems likely that Fluosol-43 with oxygen might have a synergistic effect for BCNU chemotherapy in malignant brain tumors.

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Veins draining the pineal body

An anatomical and neuroradiological study of “pineal veins”

Norihiko Tamaki, Kiyoshi Fujiwara, Satoshi Matsumoto and Hajime Takeda

✓ The authors present a detailed anatomical and neuroradiological study of the veins draining the pineal body proper, which they designate “pineal veins.” They describe three variations of the pineal veins. Since each has a characteristic angiographic relationship to the pineal body, the results of the study may permit early diagnosis of a pinealoma and distinguish the nature of the tumors of the posterior third ventricle.

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Cerebral hemodynamics in normal-pressure hydrocephalus

Evaluation by 133Xe inhalation method and dynamic CT study

Norihiko Tamaki, Tadaki Kusunoki, Toshimitsu Wakabayashi and Satoshi Matsumoto

✓ Cerebral hemodynamics in 31 patients with suspected normal-pressure hydrocephalus were studied by means of the xenon-133 (133Xe) inhalation method and on dynamic computerized tomography (CT) scanning. Cerebral blood flow (CBF) is reduced in all patients with dementia. Hypoperfusion was noted in a frontal distribution in these patients compared with normal individuals. There was no difference in CBF patterns between patients with good and those with poor outcome. The CBF was increased following cerebrospinal fluid (CSF) shunting in patients who responded to that procedure: increase in flow correlated with clinical improvement, frontal and temporal lobe CBF was most markedly increased, and the CBF pattern became normal. In contrast, CBF was decreased after shunt placement in patients who were considered to have suffered from degenerative dementia, as evidenced by non-response to shunting.

Dynamic computerized tomography studies demonstrated that patients with a good outcome showed a postoperative reduction in mean transit time of contrast material, most prominent in the frontal and temporal gray matter, and slight in the deep frontal structures, but not in the major cerebral vessels. Patients with poor outcome after shunting, however, had an increase in transit time in all regions. This corresponded well with the results as determined by the 133Xe inhalation method.