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Biomedical subjects

Akira Yamaura

Publications and source records attributed to Akira Yamaura.

At least 19 recordsLinked to original sources

Final report of the Japan Neurotrauma Data Bank project 1998-2001: 1,002 cases of traumatic brain injury.

A 4-year study (Japan Neurotrauma Data Bank) of the medical treatment of 1002 cases of traumatic brain injuries in Japan was conducted from 1998 to 2001 at 10 emergency medical centers. Patients with severe head injury were eligible for entry with a Glasgow Coma Scale score of 8 or less at admission. Patients who underwent craniotomy were also included. Children under 5 years old were excluded. An original data sheet with 392 items from multi-focal viewpoints, such as etiology of injury, pre-hospital care, initial treatment including neuro-intensive care unit, and surgical treatment, was created. The results show that the patient's age and mechanism of injury are the most important factors in the outcome.

Adolescent↗

Cathepsin D is a potential serum marker for poor prognosis in glioma patients.

Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test). Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, chi2 test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (P = 0.0081, chi2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.

Astrocytoma↗

Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats.

PURPOSE: Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/DeltaMDeltaF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model. EXPERIMENTAL DESIGN: We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy. RESULTS: We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/DeltaMDeltaF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/DeltaMDeltaF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The (51)Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4(+) T cells and CD8(+) T cells were abundantly infiltrated in the target tumors. CONCLUSION: The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.

Animals↗

Ictal dipole source analysis based on a realistic scalp-skull-brain head model in localizing the epileptogenic zone.

The objective of this study is to examine whether dipole modeling based on a realistic scalp-skull-brain head model (SSB/DT) is useful to localize the epileptogenic zone. Eight patients with surgically treated temporal lobe epilepsy were studied. Dipole locations and vector moments of ictal epileptiform activities were calculated by inverse solution methods. Accuracy of dipole locations were assessed by comparing with intracranial EEG. The patterns of ictal epileptiform activities were correlated with the dipole location and vector moment. Dipole locations of the peaks of ictal epileptiform activities estimated by SSB/DT showed good agreement with the epileptogenic foci determined by intracranial EEG. SSB/DT was able to discriminate between medial and lateral temporal epileptogenic foci. Two distinctive types of dipole vector moments, vertical and horizontal were noted. Vertical dipole vector moments corresponded to the medial temporal dipole source and horizontal dipole vector moments were corresponded to the lateral temporal dipole source. Useful clues to differentiate between medial and lateral temporal lobe epilepsy by the visual inspection of scalp EEG were found. SSB/DT is useful tool in the presurgical evaluation of patients with intractable epilepsy.

Adult↗

Successful pregnancy and delivery after removal of gonadotrope adenoma secreting follicle-stimulating hormone in a 29-year-old amenorrheic woman.

We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.

Adenoma↗

Chronic subdural haematoma after riding a roller coaster.

We report a 20-year-old man who developed a chronic subdural haematoma (CSDH) after riding a "giant" roller coaster. The patient had a past history of a subdural hygroma, diagnosed six weeks after a motorcycle accident. Three months after this accident, he rode on a roller coaster, but suffered no direct head trauma during the ride. Three weeks later, he developed a CSDH requiring surgical evacuation. Roller coaster riding, associated with high velocities and extreme acceleration/deceleration forces is a modern cause of CSDH in the young, which may be increasing due to ever-faster rides.

Accidents↗

Diagnostic value of thallium-201 chloride single-photon emission computerized tomography in differentiating tumor recurrence from radiation injury after gamma knife surgery for metastatic brain tumors.

OBJECT: The authors assessed the diagnostic value of 201Tl Cl single-photon emission computerized tomography (SPECT), performed after gamma knife surgery (GKS) for metastatic brain tumors in differentiating tumor recurrence from radiation injury. METHODS: Of 6503 metastatic brain tumors treated with GKS, 201Tl SPECT was required in 72 to differentiate between tumor recurrence and radiation injury. When the Tl index was greater than 5, the lesion was diagnosed as a tumor recurrence. When the index was < 3.0 it was called radiation injury. In cases with a Tl index between 3 and 5, 201Tl SPECT was repeated once per month until the Tl index was greater than 5 or less than 3. If the Tl index fluctuated between 3 and 5 for 2 months, the lesion was diagnosed as radiation injury. The final diagnosis was based on histological examination or clinical course. The sensitivity of the method was 91%; thus 201Tl SPECT is effective for differentiating between tumor recurrence and radiation injury in metastatic brain tumors treated with GKS. Caution is necessary, however, for the following reasons: 1) simple interinstitutional comparisons of Tl indices are not possible because measurement methods are institute specific; 2) steroid administration decreases the Tl index to a variable degree; and 3) a severe radiation injury lesion, as is often seen after repeated GKS or very high dose GKS, may have a Tl index greater than 5. CONCLUSIONS: Used with critical insight 201Tl Cl SPECT can be useful in distinguishing between tumor regrowth and radiation necrosis in patients with cerebral metastases.

Aged↗

Proteome-based identification of molecular markers predicting chemosensitivity to each category of anticancer agents in human gliomas.

To identify the protein markers that are clinically useful for predicting efficacy of anticancer agents, we investigated the correlation between the proteome profiling patterns and the in vitro chemosensitivity in human gliomas. The proteome of 93 surgical samples were analyzed with two-dimensional gel electrophoresis (2DE) and mass spectrometry. The in vitro chemosensitivities to 10 different kinds of anticancer agents (cyclophosphamide, nimustine, cisplatin, cytosine arabinoside, mitomycin C, peplomycin, adriamycin, etoposide, vincristine, paclitaxel) were measured by flow cytometric detection of apoptosis. We identified a set of 41 proteins that significantly affected the in vitro chemosensitivity to each category of anticancer agents. Many of the proteins that correlated with chemoresistance were categorized into the signal transduction proteins including the G-proteins. The present study showed that the proteome analysis using 2DE could provide a list of proteins that may be the potential predictive markers for chemosensitivity in human gliomas. They can also be direct and rational targets for anti-glioma therapy and be used for sensitization to the conventional chemotherapeutic regimens.

Antineoplastic Agents↗

MR imaging of normal perivascular space expansion at midbrain.

BACKGROUND AND PURPOSE: A previous investigation of the MR imaging findings in the midbrain reported expanded perivascular (PV) spaces in only the ponto-mesencepalic junction (PMJ) in 20% of healthy subjects, whereas pathologically expanding PV spaces have been reported at the mesencephalo-diencephalic junction (MDJ) as multi-lobulated, cystic lesions with signal intensity compatible with that of CSF that cause aqueductal stenosis. To clarify the anatomical distinctions between normally expanded and pathologically expanding PV spaces, we defined their distribution in the normal midbrain by using high-spatial-resolution MR imaging. METHODS: Heavily T2-weighted MR imaging was performed in 115 adult subjects with neurologic complaints without cerebral disease. Histologic studies were performed from two normal midbrain blocks. RESULTS: Expanded PV spaces were visible at the PMJ in 87% of subjects and at the MDJ in 63% of subjects. On axial images, ovoid or linear lesions with signal intensity compatible to CSF were present behind the cerebral peduncle at both the PMJ and MDJ. These areas varied from less than 1 mm to 5 mm (maximum diameter on coronal sections). Histologic studies confirmed the distribution of expanded PV spaces, as noted on MR images. CONCLUSION: This study, by using high-spatial-resolution MR imaging, revealed that expanded PV spaces were visible at the PMJ and MDJ. Our finding of expanded PV spaces normally present at the MDJ may be related to pathologically expanding PV spaces, which should be kept in mind as a differential diagnosis for intraparenchymal cystic lesions in the midbrain with signal intensity compatible to CSF.

Adolescent↗

Treatment of low-grade oligodendroglial tumors without radiotherapy.

The authors prospectively treated 18 consecutive patients with low-grade oligodendroglial tumors without postoperative radiotherapy. The treatment strategy was as follows: follow-up after total resection and chemotherapy after subtotal resection or biopsy. All patients were alive and 17 patients (94%) were progression-free after a median follow-up of 4.7 years. The results suggested that radiotherapy could be postponed until clinical progression in the treatment of low-grade oligodendroglial tumors.

Adult↗

Molecular classification and survival prediction in human gliomas based on proteome analysis.

The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.

Amino Acid Sequence↗

A rare case of metastatic renal cell carcinoma resembling a nerve sheath tumor of the cauda equina.

We present a rare case of solitary metastasis to the cauda equina from the kidney. The patient was a 68-year-old man with a two-year history of low back pain. His past medical history revealed a renal cell carcinoma diagnosed seven years earlier. His lumbosacral MR imaging showed a well-demarcated, intradural extramedullary mass at the L3 level. He underwent an L2-4 laminectomy. The operative findings of the tumor quite resembled that of a nerve sheath tumor. It did not infiltrate into the subarachnoid space and involved only one spinal nerve. Pathology of the tumor was a metastasis of the renal cell carcinoma. Only 10 cases with such a metastasis to the cauda equina have been reported in the English literature. We added the 11th and reviewed the literature with reference to tumor pathologies, clinical findings and route of metastasis to the cauda equina.

Aged↗

Involvement of highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive granule cells in the amygdaloid-kindling-induced sprouting of a hippocampal mossy fiber trajectory.

The mossy fiber system in the hippocampus of amygdaloid-kindled rats was examined by using highly polysialylated neural cell adhesion molecule (PSA-NCAM) as a marker for immunohistochemical detection of immature dentate granule cells and mossy fibers in combination with bromodeoxyuridine (BrdU) labeling of newly generated granule cells. Statistically significant increases in BrdU-labeled cells and PSA-NCAM-positive cells occurred in the dentate gyrus following kindling. The increase in PSA-NCAM-immunoreactive neurites was confined to the entire stratum lucidum of CA3. Immunoelectron-microscopic examination also revealed that PSA-NCAM-positive immature synaptic terminals of the sprouting mossy fibers increased in the stratum lucidum of CA3 in the kindled rats. The increase in the numbers of PSA-NCAM-positive granule cells correlated well with the increase in the immunopositive neurites and synaptic terminals on the mossy fiber trajectory. The increase in these PSA-NCAM-immunopositive structures is thought to reflect the enhancement of sprouting and synaptogenesis of mossy fibers by a subset of granule cells newly generated during amygdaloid-kindling and suggests that the reorganization of the mossy fiber system on the normal trajectory at least in part contributes to the acquisition and maintenance of an epileptogenic state.

Amygdala↗

[Nocardial brain abscess: surgery and postoperative antibiotic therapy].

Nocardial infections in an immunocompromised host have been increasingly reported. Nocardial brain abscess, the most common presentation of nocardiosis in the central nervous system, is associated with a high mortality rate because of its delayed diagnosis and its unresponsiveness to the usual antibiotic therapy. We report four patients who experienced a long-term cure of nocardial brain abscess due to treatment by a combination of surgery and postoperative antibiotic therapy; 1 man and 3 women, ages ranging from 43 to 67 years old. Two patients were associated with systemic lupus erythematosus and two with autoimmune hemolytic anemia. Patients underwent surgical aspiration and drainage of brain abscess. Nocardia was identified from the aspirated specimen and postoperative antibiotic therapy for 5-6 weeks was performed using effective antibiotic agents; sulfamethoxazole/trimethoprim (ST), imipenem/cilastatin and minocycline (MINO) in Case 1, ST and MINO in Case 2, erythromycin in Case 3, and panipenem/betamipron and cefotaxime in Case 4. Case 3 and Case 4 with multilobulated brain abscess underwent total excision of the brain abscess. All patients showed successful cure of nocardial brain abscess with no recurrence for the period of 1-8 years. The combination of surgery and postoperative antibiotic therapy provides a good prognosis for nocardial brain abscess.

Adult↗

Histologic characteristics of normal perivascular spaces along the optic tract: new pathogenetic mechanism for edema in tumors in the pituitary region.

BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.

Aged↗

Increase in metalloproteinase activity in the plasma of smoke-extract-injected rats.

Cigarette smoking is known to be one of the risk factors of subarachnoid hemorrhage (SAH), yet the precise mechanism remains to be proved. Based on the hypothesis that smoke components might enhance protease activity in the arterial wall, we examined the proteinase activities of plasma from smoke-extract-injected rats. Rats were injected intraperitoneally with smoke extract and the protease activity in the plasma was examined by zymography in the presence or the absence of proteinase inhibitors. Metalloproteinase activity was measured using a synthetic substrate. Proteolytic activities of 80- and 100-kDa against gelatin and collagen type I-V were induced 6 h after the injection. Inhibition of the activity by a metalloproteinase inhibitor but not by serine, cysteine or aspartic protease inhibitors suggested that the proteinases can be attributed to metalloproteinases. Cleavage activity in plasma toward a synthetic metalloproteinase substrate also increased within 24 h after the injection of the smoke extract. The results indicate that the induction of plasma metalloproteinase activity by smoke extract might account for the causal role of smoking in the development of SAH.

Animals↗

MR demonstration of partial lesions of the lateral geniculate body and its functional intra-nuclear topography.

Two rare cases with a partial lesion of the lateral geniculate body (LGB) presumably due to ischemia are demonstrated on high resolution MR imaging. A 62-year-old woman (case 1) presented with left homonymous superior quadrantanopia on Goldmann perimetry. Heavily T2 weighted MR images showed a localized lesion at the lateral portion of the LGB. The visual field defect was macular and horizontal meridian sparing and persisted for 9 years. A 49-year-old woman (case 2) presented with a sudden onset of left homonymous horizontal sectoranopia on Humphrey automated perimetry and heavily T2 weighted images demonstrated a lesion localized at the more medial part of the right LGB. Axons originating from inferior, central and superior retina are essentially located laterally, centrally and medially, respectively, in the LGB, based on the electrophysiological studies of animal experiments and this observation has been applied to humans. This study radiologically shows that a discrete lateral lesion of the LGB produced homonymous upper quadrantanopia in case 1, whereas a more medially located lesion produced homonymous sectoranopia in case 2, and reveals that the axons originating from inferior retina are located more laterally than those from central retina in the human LGB.

Axons↗

Intraoperative monitoring of cochlear nerve compound action potential in cerebellopontine angle tumour removal.

Cochlear nerve compound action potential (CNAP) provides a real-time auditory evoked potential. Because of technical difficulty, CNAP monitoring has not been popular during the removal of cerebellopontine angle (CPA) tumour. To clarify the efficiency of intraoperative CNAP monitoring, we designed an intracranial electrode for CNAP monitoring and performed the simultaneous monitoring of CNAP and auditory brainstem response (ABR) in 10 patients undergoing CPA tumour removal in an attempt to preserve hearing. ABR recordings during microsurgical tumour removal were unsatisfactory in 6 patients because of severe artifacts. Reliable CNAP recordings were obtained without artifacts in all 10 patients throughout surgery. Eight patients preserved useful hearing after tumour removal, and the CNAP amplitude reflected the postoperative hearing. The newly designed intracranial electrode enables CNAP monitoring predicting the postoperative hearing more reliably than ABR. CNAP monitoring is efficient to improve the hearing preservation rate following CPA tumour removal.

Action Potentials↗