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Noboru Sakai

Publications and source records attributed to Noboru Sakai.

36 records · Page 2Linked to original sources
PubMed2003

High 123I-IMP retention on SPECT image in primary central nervous system lymphoma.

The purpose of this study is to characterize the time course of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) uptake of primary central nervous system lymphomas (PCNSL) comparing with those of other common brain tumors such as malignant gliomas and meningioma. Ten patients with PCNSL, 14 with malignant gliomas and 7 with meningioma underwent 123I-IMP single photon emission computerized tomography (SPECT). Four (40%), 7 (70%) and 9 cases (90%) of PCNSL showed IMP index more than 1 on early (15 min), delayed (6 h) and extra-delayed (24 h) SPECT images, respectively. In contrast with those IMP index was less than 1 on any image of both malignant gliomas and meningioma. The PCNSL cases with IMP index more than 1 could be distinguished from malignant gliomas and meningioma visually. The mean value of IMP index of PCNSL was increased time-dependently and was higher than those of the other two brain tumor groups on SPECT images of any time phases, and statistically different from those of malignant gliomas, however, not from those of meningioma. Interestingly, the retention rates of 123I-IMP from early to extra-delayed image and delayed to extra-delayed image in PCNSL were significantly higher than those of both malignant gliomas and meningioma. The high 123I-IMP retention on SPECT image is regarded as characteristic in PCNSL and the evaluation of this character is suggested to be more useful for diagnosis of this tumor than that of 123I-IMP up-take on a single SPECT image.

Adolescent↗
PubMed2003

The use of frozen autogenous bone flaps in delayed cranioplasty revisited.

OBJECTIVE: To reevaluate the use of frozen autogenous bone flaps for patients undergoing delayed cranioplasty. METHODS: In the past 12 years, 49 patients have undergone delayed cranioplasty using frozen autogenous bone flaps. Bone flaps removed during the initial operation were sealed in three sterilized vinyl bags and stored at -35 degrees C (n = 37) or -84 degrees C (n = 12) for 4 to 168 days (mean, 50.6 d). The bone flaps were thawed at room temperature and replaced in their original positions. After cranioplasty, we monitored resorption of the bone flaps with computed tomography and evaluated the clinical and aesthetic results. Follow-up periods ranged from 14 to 147 months (mean, 59.2 mo). RESULTS: For 47 patients (95.9%), there were no complications during the follow-up period; there was slight thinning of the bone flap in some cases, but clinical and aesthetic results were highly satisfactory. Resorption was observed for a 12-year-old boy who had undergone cranioplasty, using two pieces of bone flap, 66 days after the initial operation. A 14-year-old boy with a cerebral contusion experienced a bone flap infection. Both patients underwent a second cranioplasty procedure, with ceramic plates. CONCLUSION: The clinical and aesthetic results of delayed cranioplasty using frozen autogenous bone flaps were satisfactory. The most important factor for success was excellent contiguity between the flap and the bone edge.

Adolescent↗
PubMed2003

Emergency image transfer system through a mobile telephone in Japan: technical note.

OBJECTIVE: We report the first application and usefulness of image transfer through a mobile telephone, which can be used between the hospital and another location. METHODS: With this system, brain computed tomographic scans, magnetic resonance images, and angiograms obtained from more than 100 patients in the emergency department were transferred and diagnostically analyzed via a mobile phone. The mobile phone had a 110,000-pixel digital camera and a built-in thin-film transistor liquid crystal display. We reviewed the distribution of pathological characteristics on the transferred images and compared them with the diagnoses made using full-scale original film. RESULTS: This system of transferring images was useful in all cases for correct early diagnosis and early treatment. The quality of magnetic resonance images received was better than that of computed tomographic scans. Hemorrhage provided better contrast than infarction for allowing easy identification. Cerebral angiography revealed small aneurysms if the target area was focused properly. Image quality was sufficient for interpretation despite the small dimensions of the monitor. Ease of operation and portability were both satisfactory. The mean time from commencement of image uptake to complete reception was 2 to 3 minutes. CONCLUSION: The mobile phone system is adequately useful for early diagnosis and initiation of treatment in emergent cases. This is attributable to its low cost and ease of handling for sending images to remote areas and between hospitals, despite the small dimensions of the monitor. Better-quality image transfer will be realized through an advanced mobile phone system based on the new International Mobile Telecommunication 2000 standards, which also will be useful in the development of telemedicine and telecare.

Brain Injuries↗
PubMed2003

Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note.

The authors have recently performed a fluorescence-guided tumor resection procedure by using high-dose fluorescein sodium without any special surgical microscopes for the intraoperative visualization of glioblastoma multiforme (GBM), and they report on the actual procedure and clinicopathological findings. Thirty-two patients with GBMs underwent tumor resection during which this fluorescence-guided procedure was used. Fluorescein sodium (20 mg/kg) was intravenously injected after dural opening at the craniotomy site. The tumor was stained almost homogeneously yellow and the color was intense enough to be readily perceived for resection. The center of the solid lesion was stained a deep yellow and surrounded by a transition zone that was faintly stained. The colored lesion was clearly distinguishable from the unstained zone outside the GBM, particularly in the white matter. Both the deeply and faintly stained regions included endothelial proliferation and dense tumor cells. In the unstained region, less dense tumor cells were consistently revealed; however, no endothelial proliferation could be seen. Gross-total resection (GTR) was successful in 84.4% of the patients who received an injection of fluorescein sodium, which accounted for 100% of those in whom all the visible yellow color (both the deeply and faintly stained regions) was judged to have been resected during operation. Gross-total resection was performed in 100% of the patients who underwent the fluorescence-guided procedure and assigned to Stage I, a GBM stage in which, as a therapeutic policy, the tumor should be resected as radically as possible. The GTR rates in patients who received fluorescein sodium were significantly higher than those in patients who did not (73 patients with GBMs who underwent tumor resection without the fluorescence-guided procedure). Although the extent of surgery was revealed to be one of the significant and independent prognostic factors for GBM, the fluorescein sodium-guided resection procedure was not a significant or independent prognostic factor in this series. This surgical procedure does not require any special surgical microscopic equipment and is simple, safe, useful, readily accomplished, and universally available for resection of GBMs. Its efficacy simplifies the surgical procedure of navigating the stained lesion from the unstained area to achieve GTR of GBMs, which can be demonstrated on magnetic resonance images.

Adult↗
PubMed2003

In situ detection of O6-methylguanine-DNA methyltransferase messenger RNA in paraffin-embedded human astrocytic tumor tissues by nested in situ RT-PCR is useful in predicting chemotherapy-resistance of tumors.

O6-methylguanine-DNA methyltransferase (MGMT) is an enzyme that interferes with chemotherapeutic effect of alkylating agents. We performed in situ detection of MGMT mRNA utilizing the nested RT-PCR method in tissue sections (nested in situ RT-PCR). We analyzed 34 samples of paraffin-embedded astrocytic tumor tissue sections with this method [3 astrocytomas, 14 anaplastic astrocytomas (AA), and 17 glioblastoma multiformes (GBM)]. Twenty-five cases (73.5% of all cases) were positive for MGMT either with our method or immunohistochemistry (IHC). Moreover, with our method >25% of the cells in the tumor tissue expressed MGMT in contrast to >4% with IHC among the population of MGMT positive cases. Our method was significantly more sensitive than IHC (p=0.0004). The present results suggest that potentially there is a greater population of MGMT positive cells in astrocytic tumor tissues than the one evaluated with IHC. These findings suggest that the >25% of the MGMT positive cells are involved in the interference with the chemotherapeutic effect of alkylating agents. The MGMT expressing cell population was markedly decreased in GBM compared with AA (26.1% vs 62.1%). The main reason for this marked decrease was that MGMT was expressed in only 9 of 17 cases of GBM in contrast to all AA cases that expressed MGMT. This result suggests that there are potentially two populations of GBM on the basis of MGMT expression, in which the negative population might be mainly composed of de novo GBM. Therefore, it is suggested that our method is practically useful to detect any drug resistance gene product with high sensitivity and would provide a chance to evaluate the chemotherapeutic effect of any agents in an individual patient based manner.

Astrocytoma↗
PubMed2003

[Invasive cerebral aspergillosis in an immunocompetent patient: a case report].

A 32-year-old immunocompetent female presented with sensory aphasia and psychomotor seizure due to aspergillosis in the left temporal lobe spreaded from the left orbita. In spite of oral administration of itraconazole, the symptoms continued to deteriorate due to extension of the lesion to the left temporoparietal white matter. As a result of the stereotactic biopsy of the lesion, she was histologically diagnosed as intracerebral aspergillosis. Intravenous administration of fluconazole and amphotericin B was apparently effective for the lesion, and the symptoms subsided. Ga-67 scintigram could serve as useful adjuncts to magnetic resonance images for evaluation of the therapy. This case is unusual in that an immunocompetent patient suffered from the intracerebral aspergillosis, which invasively spreaded into the parenchyma. We discussed about her pathology, diagnosis, therapy and the route of invasive aspergillosis to the parenchyma.

Adult↗
PubMed2003

[A case of a bacterial brain abscess presenting as symptoms of 'sudden stroke-like' onset].

We report a case of a bacterial brain abscess presenting symptoms of 'sudden stroke-like' onset, associated with infective endocarditis. A 59-year-old woman experienced a sudden stroke-like onset of left hemiplegia. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed on the day of ictus. No lesion responsible for the symptom was seen on either CT or a T2 weighted image (T2WI), but a diffusion-weighted image (DWI) revealed focal increased signal intensity in the right frontal lobe. An initial diagnosis of acute embolic infarction associated with infective endocarditis was made. Although the patient's neurological state had been stable, motor paresis of her left extremities became worse starting one month after her admission. MRI with gadolinium-diethylenetriaminepenta-acid (Gd-DTPA) at 37 days after admission showed an irregular-shaped ring-enhancement lesion located at the same place as the initial infarction, and in the left frontal lobe. Surgical drainage of the lesion in the right frontal lobe was performed, and diagnosed as a bacterial abscess. The exact mechanism of a bacterial brain abscess presenting with 'sudden stroke-like' onset is unknown, but various hypotheses have been proposed. One is that paroxysmal septic emboli lead to abscess formation within or near the area of embolic infarction. Our case showed that the creation of a brain abscess followed embolic strokes, and that this hypothesis was demonstrated by MRI carried out on the day of ictus.

Brain Abscess↗
PubMed2002

Increased expression and secretion of r-Gsp protein, rat counterpart of complement C1s precursor, during cyclic AMP-induced differentiation in rat C6 glioma cells.

The gene, termed r-gsp, was originally isolated during identification of differentiation-associated molecules in rat C6 glial cells. Its mRNA expression was markedly increased during cAMP-induced glial cell differentiation. The deduced amino acid sequence of r-gsp was homologous to those of complement C1s precursors of hamsters and humans. In the present study, we raised anti-peptide antibody against r-Gsp protein and analyzed its change during cAMP-induced differentiation. The 90-kDa r-Gsp protein increased time-dependently and reached the maximal level ( approximately 7.6-fold increase) at 24 h in response to dibutyryl cyclic AMP (dbcAMP) and theophylline. Moreover, it was secreted into the medium and then was cleaved to form disulfide-linked fragments, one of which was 30 kDa, similar to C1s, suggesting its processing in the extracellular space. In fact, the partially purified r-Gsp from culture medium was cleaved by active human C1r to form a 30-kDa polypeptide. Moreover, secreted r-Gsp protein cleaved human C4alpha to yield C4alpha' and associated with human serum C1-esterase inhibitor, strongly suggesting that r-Gsp protein is rat C1s. However, in C6 cells overexpressing r-Gsp, their morphology and proliferation rate were similar to those in parent C6 cells. These results suggest that r-Gsp protein could not induce glial differentiation alone, and suggest that r-Gsp protein was secreted as a proenzyme and processed in culture medium. Its possible role in glial cell differentiation will be discussed.

Animals↗
PubMed2002

Acid sphingomyelinase activation requires caspase-8 but not p53 nor reactive oxygen species during Fas-induced apoptosis in human glioma cells.

During apoptosis of human glioma cells induced by anti-Fas antibody, ceramide formation with activation of acid, but not neutral sphingomyelinase (SMase), was observed. A potent inhibitor of acid SMase, SR33557, effectively inhibited ceramide formation and apoptosis. Fas-induced apoptosis and ceramide formation proceeded regardless of p53 status. The agents, which modify intracellular levels of reactive oxygen species (ROS) and reduced glutathione (GSH), failed to modulate Fas-induced acid SMase activation and apoptosis. Moreover, expression of functional p53 protein using a temperature-sensitive human p53val(138) induced ceramide generation by activation of neutral SMase but not acid SMase through ROS formation. Peptide inhibitors for caspases-8 (z-IETD-fmk) and -3 (z-DEVD-fmk) suppressed Fas-induced apoptosis. However, activation of acid SMase was inhibited only by z-IETD-fmk. Thus, ceramide generated by acid SMase may take a part in Fas-induced apoptosis of human glioma cells and acid SMase activation may be dependent on caspase-8 activation, but not on p53 nor ROS.

Apoptosis↗
PubMed2002

Radiological response and histological changes in malignant astrocytic tumors after stereotactic radiosurgery.

Stereotactic radiosurgery is an encouraging approach to deliver higher doses of radiation boost for malignant gliomas safely and precisely. The purpose of this study was to investigate the radiation response and histological changes of malignant astrocytic tumors after stereotactic linac radiosurgery (SLRS). We studied an autopsy case of recurrent glioblastoma multiforme (GBM) and two surgical cases with gross total removal of recurrent GBM and anaplastic astrocytoma transformed from fibrillary astrocytoma treated with SLRS. Destructive changes, such as the disappearance of viable cells, coagulation necrosis, and fibrinoid degeneration of vascular walls, were observed in the center of the target of SLRS, which showed histologically similar radiobiological reactions to well-known delayed central nervous system radiation necrosis caused by conventional radiotherapy. The region showing such radiation necrosis was within the area irradiated with approximately 15-20Gy or more by SLRS; however, dense viable tumor cells remained in the periphery that was irradiated with less than 15Gy. In a comparative immunohistochemical study of the tumors before and after SLRS, neither MIB-1 and p53 labeling indices nor immunoreactivity for GFAP represented any persistent tendencies. There were very few TUNEL-positive cells in either tumor before and after SLRS. These results showed that radiosurgery for malignant gliomas leads to earlier radiation necrosis than conventional radiation and that it is useful in eradicating tumor cells in the center of the target. However, some viable tumor cells may remain in the periphery irradiated with an insufficient dose for cell death and may be partly transformed in character by DNA damage due to radiation. Proton magnetic resonance spectroscopy (MRS) was suggested to characterize the radiation response in radiosurgery tumor targets for correlation with histological findings.

Adult↗
PubMed2002

Nestin immunoreactivity in local neurons of the adult rat striatum after remote cortical injury.

Nestin is a marker for the neuronal and glial precursor cells and is expressed in reactive astrocytes after brain injury. Following restricted neocortical injury, we found that cells with neuronal morphology in the adult rat striatum became immunoreactive for both nestin and the neuronal marker, microtubule-associated protein 2 (MAP-2), but not for the astroglial marker, glial fibrillary acidic protein (GFAP). The number of nestin-positive cells transiently increased in the striatum. Continuous administration of 5-bromo-2'-deoxyuridine (BrdU) after cortical injury did not reveal any newly generated neurons in the striatum. Double-labeling fluorescent immunocytochemistry revealed that the nestin-positive striatal cells were also substance-P-positive. These findings suggest that some factors released from the injured cortex may induce nestin immunoreactivity in striatal neurons.

Animals↗
PubMed2002

Gene transfer of hepatocyte growth factor to subarachnoid space in cerebral hypoperfusion model.

Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that beta-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using beta-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P<0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P<0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P<0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P<0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.

Animals↗
PubMed2002

Failure of B7.1-modified tumor to evoke full activation of CD8+ tumor-infiltrating lymphocytes in the central nervous system: prevention of parental tumor growth in the subcutaneous environment.

OBJECT: It is well known that the central nervous system (CNS) is an immunologically privileged site. To characterize CD8+ tumor-infiltrating lymphocytes (TILs) recovered from the CNS, the authors compared these cells with TILs recovered from subcutaneous tissue by using a B7.1 gene-modified tumor implantation model. METHODS: The authors established a B7.1 gene-modified EL4 murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to observe the duration of tumor-free survival. Although EL4-B7.1 cells were completely rejected in a subcutaneous implantation model, 40% of animals died after the CNS implantation (all animals in which the parent tumor was implanted died within 16 days). Therefore, the authors isolated TILs from each implantation site and analyzed the expressions of activation antigens CD25 and CD69 by performing the anti-CD8 magnetic beads separation method and flow cytometric analysis. After implantation of the parent tumor, there was no difference in the number of TILs from each site (CD25 1.7-3.2%, CD69 21.9-34.3%). After implantation of the B7.1-modified tumor, the CD25-expressing TIL population from the subcutaneous site was 4.68 times higher than that from the CNS site (17.8% compared with 3.8%). Based on these findings, the authors used a mitomycin C-treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination before tumor challenge was sufficient to prevent the development of the tumor. For animals with established tumor, the vaccination protocol was able to prolong host survival (p = 0.0053). CONCLUSIONS: The data clearly demonstrate that the CNS environment fails to activate CD8+ TILs fully. These are the first data indicating in detail a difference between CD8+ TILs from the CNS and those from other sites based on a B7.1-modified tumor model.

Animals↗
PubMed2002

[An automated detection of lacunar infarct regions in brain MR images: preliminary study].

The purpose of this study is to develop a technique to detect lacunar infarct regions automatically in brain MR images. Our detection method is based on the definition of lacunar infarcts. After inputted images were binarized, we used feature values such as area, circularities and the center of gravity of candidate regions to extract isolated lacunar infarct regions. We also developed and used a new filter to enhance the signals of lacunar infarcts adjacent to some high intensity regions. 10 cases involving 81 sectional images were applied to our experiment. As a result, the sensitivity was 100% with approximately 1.77 false-positives per image. Our results are promising on the first stage, although it remains to improve on problems that to eliminate false-positives and automatically establish threshold value.

Cerebral Infarction↗
PubMed2002

B7.1 immunogene therapy effectively activates CD(4+) tumor-infiltrating lymphocytes in the central nervous system in comparison with B7.2 gene therapy.

The B7 gene utilizing immunogene therapy is one of the most common methods against tumor growth. However, there is no known study that investigated the difference between B7.1 and B7.2 with regard to B7 gene therapy in the central nervous system (CNS). Therefore, to clarify the difference, we established B7.1 or B7.2 gene transduced tumor cells originating from the murine T cell lymphoma cell line EL4 (EL4-B7.1 or EL4-B7.2). First, we observed the survival time after intracranial inoculation of parent (IC-wt) or genetically modified tumor cells. All mice in control groups (IC-wt or IC-mock) were dead within 16 days. While there was significant survival elongation in the B7.2 modified group (IC-B7.2, p=0.0002), all mice in this group were dead of tumor growth within 22 days. On the other hand, 60% of mice inoculated with EL4-B7.1 (IC-B7.1) survived more than 120 days (p<0.0001). Second, to shed light on the anti-tumor immune response in situ, we tried to analyze CD(4+) tumor-infiltrating T lymphocytes (CD(4+) TIL). To purify and analyze CD(4+) TIL, we had to deplete F4/80(+) microglia because of the CD4 expression. In terms of activation marker expression in CD(4+) TIL, a small population was activated (CD25, 9.8%; CD69, 15.8%) in the control group (IC-wt). In contrast, the activation marker positive CD4+ TIL percentage both in IC-B7.1 (CD25, 25.1%; CD69, 40.1%) and IC-B7.2 (CD25, 16.2%; CD69, 28.3%) appeared to reflect the survival curve in both groups. These findings strongly suggest that, in the CNS, B7.1 gene therapy could effectively introduce CD(4+) TIL activation compared with B7.2 gene therapy. This is the first study clearly describing the difference between B7.1 gene therapy and B7.2 gene therapy in the CNS in terms of the activation status of CD(4+) TIL in situ.

Animals↗
PubMed2002

[Evaluation of cerebral hemodynamics with perfusion CT].

We report on the evaluation of cerebral ischemic lesions with perfusion CT. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of 52 patients mostly with ischemic cerebrovascular disease were analysed using the box-modulation transfer function method with 30 ml of contrast medium intravenously injected at 5 ml/sec. CBF, CBV and MTT of the middle cerebral artery (MCA) territory were 43.5 +/- 4.6 ml/100 g/min, 1.9 +/- 0.2 ml/100 g and 2.9 +/- 0.6 seconds at the unaffected side, and 37.7 +/- 7.3 ml/100 g/min, 2.1 +/- 0.3 ml/100 g, 3.7 +/- 0.9 seconds at the lesion side with stenosis or occlusion in the main MCA trunks or internal carotid artery, respectively. A statistically significant difference was shown in CBF and MTT values. Furthermore, there was a close correlation in CBF values of MCA territories between Xe-CT and perfusion CT (r = 0.645, n = 76, p < 0.0001). MTT showed a positive correlation with CBV in those subjects when MTT was below 4.1 seconds (r = 0.526, p < 0.0001, n = 83). MTT also showed a negative correlation with CBF in those patients when MTT indicated more than 4.1 seconds (r = 0.818, p < 0.001, n = 21). These results suggest that the progression of cerebral ischemia may be classified in 4 stages using perfusion CT. The stages are as follows: stage 0; normal CBF without prolonged MTT and increased CBV, stage 1; relatively increased CBV, stage 2; significantly prolonged MTT, and stage 3; significantly decreased CBF with prolonged MTT.

Adult↗