✓ The 47-year-old man reported here showed large encapsulated masses in the left cerebellopontine angle and 6 years later in the enlarged left jugular foramen. Histologically, the tumors demonstrated a large deposit of amyloid composed of immunoglobulin light chain-derived proteins (AL). There was no evidence of chronic inflammatory or infectious processes or immunoglobulin abnormalities.
Tsuyoshi Matsumoto, Eiichi Tani, Yukio Maeda, and Shigeatsu Natsume
Keizo Kaba, Eiichi Tani, Tatsuo Morimura, and Tsuyoshi Matsumoto
✓ The effects of calcium channel blockers and calmodulin inhibitors on vincristine cytotoxicity were studied in vitro with five glioma cell lines: three human glioblastomas, one rat glioma, and one mouse ependymoblastoma. One human glioblastoma and the rat glioma were resistant to vincristine in contrast to other glioma cells. The resistance to vincristine was considerably decreased by nontoxic or marginally toxic concentrations of calcium channel blockers or calmodulin inhibitors, although the former was more effective than the latter. In the presence of verapamil, the vincristine cytotoxicity, as measured by cell doubling times, increased 90- and 84-fold in the vincristine-resistant human glioblastoma and rat glioma, respectively. The decrease in the resistance to vincristine was related to a marked increase in the intracellular level of that drug, probably mediated by inhibiting its outward transport. The in vivo studies showed that verapamil or nicardipine administered daily with vincristine for 10 days significantly enhanced the chemotherapeutic effect of vincristine in an intracranially transplanted rat glioma model. An approximately 32% to 118% increase in life span occurred with 15 mg/kg/day of verapamil, depending on the doses of vincristine.
Yukio Maeda, Eiichi Tani, Masaru Nakano, and Tsuyoshi Matsumoto
✓ The case is presented of a 36-year-old woman with a plasma-cell granuloma arising in the fourth ventricle. The mass appeared on computerized tomography as a well circumscribed area of slightly high density that was markedly enhanced with contrast medium. Microscopic examination showed a mixed-cell population with a predominance of plasma cells, and the tumor was characterized immunohistochemically by polyclonal plasma-cell proliferation.
Tsuyoshi Matsumoto, Eiichi Tani, Keizo Kaba, Hideki Shindo, and Katsuya Miyaji
✓ The expression of P-glycoprotein, a product of multidrug resistance gene 1, was studied by Western blotting and immunohistochemistry in five human glioma cell lines. One glioma cell line was resistant to vincristine, Adriamycin (doxorubicin), and etoposide, and the other four glioma cell lines were sensitive to each drug. The multidrug-resistant cell line showed a high expression of P-glycoprotein in Western blot analysis and a positive immunostaining for P-glycoprotein mainly along the cell membrane, whereas all multidrug-sensitive glioma cell lines demonstrated no expression of P-glycoprotein in Western blotting and no immunostaining for P-glycoprotein, thus showing a good correlation between the expression level of P-glycoprotein and the extent of multidrug resistance.
In 18 human surgical glioma specimens, there was no evidence of complete absence of immunostaining for P-glycoprotein. With a definition of more than 20% of P-glycoprotein-positive cells as positive, from 10% to 20% as intermediate, and less than 10% as negative, immunostaining for P-glycoprotein was positive in one specimen and intermediate in six of 15 specimens taken from virgin gliomas, and positive in two specimens and intermediate in one of three recurrent gliomas treated previously with irradiation, ACNU (1-(4-amino-2-methyl-pyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), cisplatin, vincristine, and/or procarbazine.
Tomiya Matsumoto, Shinya Okuda, Takafumi Maeno, Tomoya Yamashita, Ryoji Yamasaki, Tsuyoshi Sugiura, and Motoki Iwasaki
The importance of spinopelvic balance and its implications for clinical outcomes after spinal arthrodesis has been reported in recent studies. However, little is known about the relationship between adjacent-segment disease (ASD) after lumbar arthrodesis and spinopelvic alignment. The purpose of this study was to clarify the relationship between spinopelvic radiographic parameters and symptomatic ASD after L4–5 single-level posterior lumbar interbody fusion (PLIF).
This was a retrospective 1:5 matched case-control study. Twenty patients who had undergone revision surgery for symptomatic ASD after L4–5 PLIF and had standing radiographs of the whole spine before primary and revision surgeries were enrolled from 2005 to 2012. As a control group, 100 age-, sex-, and pathology-matched patients who had undergone L4–5 PLIF during the same period, had no signs of symptomatic ASD for more than 3 years, and had whole-spine radiographs at preoperation and last follow-up were selected. Mean age at the time of primary surgery was 68.9 years in the ASD group and 66.7 years in the control group. Several radiographic spinopelvic parameters were measured as follows: sagittal vertical axis (SVA), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), and segmental lordosis at L4–5 (SL) in the sagittal view, and C7–central sacral vertical line (C7-CSVL) in the coronal view. Radiological parameters were compared between the groups.
No significant change was found between pre- and postoperative radiographic parameters in each group. In terms of preoperative radiographic parameters, the ASD group had significantly lower LL (40.7° vs 47.2°, p < 0.01) and significantly higher PT (27° vs 22.9°, p < 0.05) than the control group. SVA ≥ 50 mm was observed in 10 of 20 patients (50%) in the ASD group and in 21 of 100 patients (21%, p < 0.01) in the control group. PI-LL ≥ 10° was noted in 15 of 20 patients (75%) in the ASD group and in 40 of 100 patients (40%, p < 0.01) in the control group on preoperative radiographs. Postoperatively, the ASD group had significantly lower TK (22.5° vs 30.9°, p < 0.01) and lower LL (39.3° vs 48.1°, p < 0.05) than the control group had. PI-LL ≥ 10° was seen in 15 of 20 patients (75%) in the ASD group and in 43 of 100 patients (43%, p < 0.01) in the control group.
Preoperative global sagittal imbalance (SVA > 50 mm and higher PT), pre- and postoperative lower LL, and PI-LL mismatch were significantly associated with ASD. Therefore, even with a single-level PLIF, appropriate SL and LL should be obtained at surgery to improve spinopelvic sagittal imbalance. The results also suggest that the achievement of the appropriate LL and PI-LL prevents ASD after L4–5 PLIF.
Yukitaka Nagamoto, Motoki Iwasaki, Shinya Okuda, Tomiya Matsumoto, Tsuyoshi Sugiura, Yoshifumi Takahashi, and Masayuki Furuya
Surgical management of massive ossification of the posterior longitudinal ligament (OPLL) is challenging. To reduce surgical complications, the authors have performed anterior selective stabilization combined with laminoplasty (antSS+LP) for massive OPLL since 2012. This study aimed to elucidate the short-term outcome of the antSS+LP procedure.
The authors’ analysis was based on data from 14 patients who underwent antSS+LP for cervical myelopathy caused by massive OPLL and were followed up for at least 2 years after surgery (mean follow-up duration 3.3 years). Clinical outcome was evaluated preoperatively, at 6 months and 1 year postoperatively, and at the final follow-up using the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy and the recovery rate of the JOA score. The following radiographic parameters were measured preoperatively, immediately after surgery, at 1 year after surgery, and at the final follow-up: the C2–7 angle, measured on lateral plain radiographs, and the segmental lordosis angle (SLA), measured on sagittal CT scans. The correlation between radiographic parameters and clinical outcomes was evaluated.
The mean JOA score increased from 10.4 before surgery to 13.6 and 13.8 at 6 months and 1 year after surgery, respectively; at the final follow-up the mean score was 13.4. This postoperative recovery was significant (p = 0.004) and was maintained until the final follow-up. No patient required revision surgery due to postoperative neurological deterioration. However, the C2–7 angle gradually deteriorated postoperatively. Similarly, the SLA was significantly increased immediately after surgery, but the improvement was not maintained. The recovery rate at the final follow-up correlated positively with the change in C2–7 angle (r = 0.60, p = 0.03) and the change in SLA (r = 0.72, p < 0.01).
AntSS+LP is safe and effective and may be an alternative to anterior decompression and fusion for the treatment of patients with massive OPLL. No postoperative neurological complications or significant postoperative exacerbation of neck pain were observed in our case series. Not only reducing intervertebral motion and decompressing the canal at the maximal compression level but also acquiring segmental lordosis at the maximal compression level are crucial factors for achieving successful outcomes of antSS+LP.
Motohiko Sato, Eiichi Tani, Tsuyoshi Matsumoto, Hirokazu Fujikawa, and Shinobu Imajoh-Ohmi
In previous studies of topical application of calphostin C, a specific inhibitor of the regulatory domain of protein kinase C (PKC), and calpeptin, a selective inhibitor of calpain, to spastic canine basilar artery (BA) researchers have suggested that the catalytic fragment of PKC (known as PKM) is probably formed by a limited proteolysis of continuously activated μ-calpain, but there has been no direct evidence for PKM formation in vasospasm. The present immunoblot study with anti-PKC-alpha antibody shows a significant decrease in cytosolic 80-kD PKC-alpha and a concomitantly significant increase in membrane PKC-alpha in the spastic canine BA. In addition, an immunoblot study in which cleavage site-directed antibodies were used demonstrated a significant increase in immunoreactive 45-kD PKM. The changes in membrane PKC-alpha and PKM were enhanced with the lapse of time after subarachnoid hemorrhage. The cleavage site-directed antibodies distinguish the proteolyzed from the unproteolyzed forms of PKC for in situ analyses of enzyme regulation mediated by proteolysis. The data indicate that PKC-alpha in spastic canine BA is translocated to the cell membrane, where PKC-alpha is rapidly cleaved into PKM as a result of proteolysis of the isozyme by μ-calpain but not by m-calpain. The authors hypothesize that μ-calpain is continuously activated in spastic canine BA and produces PKM by limited proteolysis of PKC-alpha.
Ikuya Yamaura, Eiichi Tani, Masayuki Yokota, Atsuhisa Nakano, Masahiro Fukami, Keizo Kaba, and Tsuyoshi Matsumoto
Object. Surgical or endovascular occlusion of the parent artery proximal to an aneurysm has been recommended for treatment of dissecting aneurysms of the intracranial posterior circulation. However, dissecting aneurysms may rupture even after proximal occlusion because distal progression of thrombus is necessary to occlude the dissecting aneurysm completely, and this may be delayed by the presence of retrograde flow. In this article the authors present their experience in treating six patients with ruptured dissecting aneurysms.
Methods. The authors report on six patients with a ruptured dissecting aneurysm in the posterior fossa who were successfully treated by endovascular occlusion of the aneurysm by using Guglielmi detachable coils. The procedure was particularly aimed at occluding the dissected site.
Conclusions. At the present time, endovascular occlusion of the dissected site is a safe, minimally invasive, and reliable treatment for dissecting aneurysms when a test occlusion is tolerated and adequate collateral circulation is present.
Motohiko Sato, Eiichi Tani, Tsuyoshi Matsumoto, Hirokazu Fujikawa, and Shinobu Imajoh-Ohmi
✓ In previous studies of topical application of calphostin C, a specific inhibitor of the regulatory domain of protein kinase C (PKC), and calpeptin, a selective inhibitor of calpain, to spastic canine basilar artery (BA) researchers have suggested that the catalytic fragment of PKC (known as PKM) is probably formed by a limited proteolysis of continuously activated µ-calpain, but there has been no direct evidence for PKM formation in vasospasm. The present immunoblot study with anti-PKCα antibody shows a significant decrease in cytosolic 80-kD PKCα and a concomitantly significant increase in membrane PKCα in the spastic canine BA. In addition, an immunoblot study in which cleavage site—directed antibodies were used demonstrated a significant increase in immunoreactive 45-kD PKM. The changes in membrane PKCα and PKM were enhanced with the lapse of time after subarachnoid hemorrhage. The cleavage site—directed antibodies distinguish the proteolyzed from the unproteolyzed forms of PKC for in situ analyses of enzyme regulation mediated by proteolysis. The data indicate that PKCα in spastic canine BA is translocated to the cell membrane, where PKCα is rapidly cleaved into PKM as a result of proteolysis of the isozyme by µ-calpain but not by µ-calpain. The authors hypothesize that µ-calpain is continuously activated in spastic canine BA and produces PKM by limited proteolysis of PKCα.
Hideyasu Ikemoto, Eiichi Tani, Tsuyoshi Matsumoto, Atsuhisa Nakano, and Jun-Ichi Furuyama
✓ Calphostin C acts at the regulatory domain as a highly selective inhibitor of protein kinase C (PKC), and staurosporine acts at the catalytic domain as a nonspecific PKC inhibitor. The authors investigated the capacity of calphostin C and staurosporine to promote apoptotic fragmentation of DNA in four human glioma cell lines. The exposure of glioma cell lines to 100 nM calphostin C for 2 to 8 hours induced a decrease in particulate PKC activities and exposure for 16 to 24 hours produced a concentration-dependent increase in internucleosomal DNA cleavage on agarose gel electrophoresis. In addition, the human glioma cells showed the classic morphological features of apoptosis: cell shrinkage, nuclear condensation, and the formation of apoptotic bodies. A 24-hour exposure to staurosporine failed to induce internucleosomal DNA fragmentation at concentrations generally used to achieve maximum inhibition of enzyme activity (50 nM) but promoted fragmentation at considerably higher concentration (more than 200 nM). Deoxyribonucleic acid fragments obtained from cells exposed to 100 nM calphostin C for 16 to 24 hours possessed predominantly 59-phosphate termini, consistent with the action of a Ca++/Mg++-dependent endonuclease. Northern and Western blot analyses revealed that the exposure to 100 nM calphostin C for 4 hours failed to alter bcl-2 transcript and protein, but exposure for more than 8 hours decreased the amount of bcl-2 transcript and protein. Together, these observations suggest that calphostin C is capable of inducing apoptotic DNA fragmentation and cell death in a highly concentration dependent manner in human glioma cells and that the apoptosis is closely associated with the decrease in transcription and translation of bcl-2.