Biomedical subjects

Eiji Kohmura

Publications and source records attributed to Eiji Kohmura.

At least 19 recordsLinked to original sources

PubMed2005

Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1.

Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.

Amino Acid Sequence↗

PubMed2005

Involvement of gamma protein kinase C in estrogen-induced neuroprotection against focal brain ischemia through G protein-coupled estrogen receptor.

The neuroprotective effects of estrogen were studied in the ischemic model mice by 90 min transient unilateral middle cerebral artery occlusion (MCAO) followed by 22.5 h reperfusion. The total infarct size in C57BL/6 female mice after MCAO and reperfusion was significantly smaller than that in male mice. Intraperitoneal injection of estrogen after the start of reperfusion significantly reduced the infarct volume in the male mice. However, no significant gender difference was found in total infarct size in gamma protein kinase C (PKC)-knockout mice, suggesting that the neuroprotective effects of estrogen are due to the activation of a specific subtype of PKC, gammaPKC, a neuron-specific PKC subtype, in the brain. We demonstrated that exogenous estrogen-induced neuroprotection was attenuated in gammaPKC-knockout mice. Immunocytochemical study showed that gammaPKC was translocated to nerve fiber-like structures when observed shortly after MCAO and reperfusion. We also visualized the rapid and reversible translocation of gammaPKC-GFP (green fluorescent protein) by estrogen stimulation in living CHO-K1 cells. These results suggest that the activation of gammaPKC through the G-protein-coupled estrogen receptors on the plasma membrane is involved in the estrogen-induced neuroprotection against focal brain ischemia.

Animals↗

PubMed2005

Treatment of cerebral vasospasm with intra-arterial fasudil hydrochloride.

OBJECTIVE: Symptomatic cerebral vasospasm is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage. The purpose of this study was to determine the efficacy of intra-arterial infusion (IAF) of fasudil hydrochloride for symptomatic vasospasm in terms of neurological improvement and the angiographic features of cerebral vessels. METHODS: A consecutive series of 23 patients underwent IAF therapy for the treatment of symptomatic vasospasm after subarachnoid hemorrhage. Angiographic vasospasm was assessed before and after the IAF treatment. Immediate clinical effect was assessed within 24 hours after the IAF treatment, and the Glasgow Outcome Scale was used to evaluate late clinical outcome at 3 months after the onset. RESULTS: IAF treatment was performed on 34 occasions for 23 patients (16 women, 7 men). Angiographic improvement was observed on all occasions (100%), and immediate clinical improvement was observed on 15 occasions (44.1%). At 3-month follow-up, 15 patients (65.2%) showed good recovery or moderate disability on the Glasgow Outcome Scale. CONCLUSION: IAF therapy was effective in dilating spastic arteries, and clinical improvement was observed in approximately half of the fasudil hydrochloride infusions. Our findings suggested that the IAF therapy was safe and effective for patients with symptomatic vasospasm after subarachnoid hemorrhage.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

Comparison of conventional region of interest and statistical mapping method in brain single-photon emission computed tomography for prediction of hyperperfusion after carotid endarterectomy.

OBJECTIVE: Hyperperfusion after carotid endarterectomy (CEA) has been proposed as the main mechanism of intracerebral hemorrhage, which is a disastrous complication. The aim of this study was to compare the predictive value of cerebral blood flow (CBF) abnormalities for hyperperfusion after CEA with the conventional region of interest (ROI) analysis and statistical brain mapping analysis. METHODS: For 46 patients with unilateral carotid stenosis of 70% or more, CBF and cerebral vasoreactivity were investigated with resting and acetazolamide-challenge single-photon emission computed tomography before CEA and 1 day after CEA. Three-dimensional stereotactic surface projection (3-D-SSP) analysis of CBF changes was performed by automatic quantification with a predefined template. RESULTS: Logistic regression analysis demonstrated CBF reduction (z-score) to be the only significant variable for postoperative hyperperfusion on 3-D-SSP with thalamic normalization but no significant variable with the ROI method. Receiver operating characteristic (ROC) analysis demonstrated significant improvement in the predictive value of CBF reduction (z-score) on 3-D-SSP (area under the ROC curve = 0.93) in comparison with the ROI method (area under the ROC curve = 0.78) (P = 0.049). According to the optimal cutoff values provided by ROC analysis, patients were categorized into two groups: Type I (CBF decrease < 20%, n = 23) and Type II (CBF decrease > or = 20%, n = 23) on ROI analysis and Type A (z-score < or = 2, n = 40) and Type B (z-score > 2, n = 6) on 3-D-SSP. There was a significant difference in incidence of hyperperfusion between Type A (1 of 40) and Type B (5 of 6) on 3-D-SSP (P = 0.00003) but not between Type I (1 of 23) and Type II (5 of 23) on ROI analysis. Cerebral vasoreactivity did not show significant value in the prediction of hyperperfusion with either the ROI or the 3-D-SSP method. CONCLUSION: Objective assessment of CBF status, especially baseline CBF reduction (z-score), with automatic quantification by 3-D-SSP with normalization had a higher diagnostic value than conventional ROI analysis to identify patients at risk for hyperperfusion after CEA.

Acetazolamide↗

PubMed2005

Knife blade penetrating stab wound to the brain--case report--.

A 28-year-old man attempted to kill himself with a knife stab into the parietal area. Neuroimaging showed no vascular impairment except slow venous flow around the knife due to tamponading. After obtaining informed consent, the knife was removed through a craniotomy without new brain injury. Postoperative neurological findings showed no deficit. Follow-up angiography revealed no vascular impairment. No infection occurred. Brain stab wounds cause numerous complications, such as intracranial hemorrhage, injury of important vessels, and infections. Minimal blade movement during removal and precautions to prevent massive hemorrhage are essential.

Adult↗

PubMed2005

Acquired lumbar epidermoid cyst in an adult.

A 61-year-old female complained of low back pain, and had been treated by spinal anesthetic injection more than 70 times over 14 years. Magnetic resonance (MR) imaging, performed at the age of 47 years, revealed no abnormal lesion. However, she developed irritable hypesthetic pain in the left leg at 61 years of age. MR imaging revealed a round mass appearing isointense on the T1-weighted and slightly hyperintense on the T2-weighted images. Laminectomy revealed an epidermoid cyst, which was removed. This case clearly demonstrates that adults can acquire epidermoid tumor which very probably has an iatrogenic origin. The incidence of epidermoid tumor is low, but we should be aware of the potential adverse complications such as formation of epidermoid tumors after lumbar puncture.

Epidermal Cyst↗

PubMed2005

[A case of subacute combined degeneration of the spinal cord diagnosed by characteristic findings of magnetic resonance imaging: case report and review of 22 cases].

Subacute combined degeneration (SCD) is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord, and is a neurogenic complication due to vitamin B12 deficiency. This report concerns a patient with progressive sensory disturbance, but no abnormal neurological findings. A 73-year-old man with gastrectomy presented with a 6-month history of gradually worsening tingling in both hands. Magnetic resonance imaging (MRI) of the cervical spine clearly showed symmetrical high-signal areas on T2WI involving the posterior columns of the cervical cord from C2 through C6. A diagnosis of SCD of the spinal cord was considered and confirmed by laboratory findings. The patient was treated with vitamin B12 supplements and showed gradual improvement in his clinical symptoms. Repeat MRI of the cervical spine after 3 months indicated a slight decrease in the area of the abnormal signal. Among all the possible causes of myelopathy, SCD of the spinal cord, involving neurological complications due to vitamin B12 deficiency, is one of the less often encountered diseases. Nevertheless, SCD should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.

Aged↗

PubMed2004

Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice.

Adult green mice marrow stromal cells were co-cultured with hippocampal slices. Differentiation to neuron-like or non-neuron-like cells occurred exclusively inside slice boundaries starting at day 3, and then decreased gradually over 35 days. Neuron-like cells tended to form network-like connections around day 14. The use of retinoic acid greatly increased the number of differentiated cells, and the most effective concentration was 10(-6) M. NeuN immunohistochemistry was positive in 9.6+/-1.7% of morphologically differentiated neuron-like cells. Both GFAP and Iba1 immunostaining were negative. We concluded that bone marrow stromal cells can be differentiated into neurons, and direct contact with the host brain tissue is essential for this to occur. Retinoic acid significantly increases the number of differentiated cells, as has been reported with other stem cells.

Animals↗

PubMed2004

In vivo transgene expression using an adenoviral tetracycline-regulated system with neuron-specific enolase promoter.

A recombinant adenoviral tetracycline-regulated system with neuron-specific enolase (NSE) promoter was injected stereotaxically into the striatum of rat brains. The efficiency of in vivo transfection was quantified by counting the number of green fluorescent protein (GFP)-positive cells at 3 days, 1 week, and 4 weeks after injection. NeuN immunohistochemistry demonstrated that expression of gammaPKC-GFP was dominant (20-99%) in neuron and expression of gammaPKC-GFP in neuron was significantly higher in pups than adult rats. These results indicate that tetracycline-inhibitable transcription factor (tTA) can drive tetracycline-responsive promoter (TetOp) under the control of NSE promoter, thereby efficiently and selectively expressing gammaPKC-GFP in neurons in vivo.

Adenoviridae↗

PubMed2004

Cytological and bacteriological studies of intraoperative autologous blood in neurosurgery.

BACKGROUND: To ensure the safety of salvaged blood in neurologic surgery, reinfused blood through the Cell Saver System (CSS) (Hemonetics) was investigated cytologically and bacteriologically. METHODS: Specimens of reinfused blood were cytologically examined with Papanicolaou or Giemsa stains. Reinfused blood and air in the operating theater were investigated by microbiologic techniques. The concentration of dust particles in the theater was determined. RESULTS: Tumor cells were positive in reinfused blood in 5 of 9 specimens with glioblastoma, in 2 of 8 with pituitary adenoma, and 1 of 13 with meningioma. The probability of migration of meningioma cells into reinfused blood was significantly low in comparison with that of glioma cells. Of the 30 specimens studied microbiologically, the bacterial growth was detected in salvaged blood of 14 specimens (46.7%) and in the air of the operating theater for 8 specimens (26.7%). In craniotomy, the contamination rate was 10 of 26 specimens of reinfused blood (38.5%). Most microorganisms were found to be staphylococci. No statistically significant correlation could be found between salvaged blood and air as to contamination or between reinfused blood and the concentration of dust particles in the theater as to bacteriologic results. No infectious complications were found after the operation, though salvaged blood through the CSS was reinfused in 37 patients without glioblastoma or transsphenoidal approach. CONCLUSIONS: The CSS cannot always entrap tumor cells. Salvaged blood should not be reinfused in the patients with glioblastoma or transsphenoidal surgery. None of the patients with reinfusion had any infectious complications. Reinfusion of salvaged blood seems to be safe in neurosurgery.

Blood↗

PubMed2004

Src family kinase inhibitor PP1 reduces secondary damage after spinal cord compression in rats.

The synthetic pyrazolopyrimidine, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) is a novel, potent, and selective inhibitor of Src family tyrosine kinases. Vascular permeability appears to be mediated by vascular endothelial growth factor (VEGF), which requires the activation of downstream Src family kinases to exert its function. This study investigates the effects of PP1 on vascular permeability and inflammatory response in a rat spinal cord compression model. Ten minutes after compression, PP1 (PP1 group) or the vehicle only (control group) was administered. On days 1, 3, and 7 after compression, the spinal cords were removed and examined histopathologically to determine the expression of VEGF and the extent of edema and inflammation. The dryweight method was used to measure the water content of the spinal cords. The mRNA levels of tumor necrosis factor a (TNFalpha) and interleukin 1beta (IL-1beta), which is related to inflammatory responses, were measured with a real-time polymerase chain reaction (RT-PCR) system 6 h after compression. Although VEGF expression was similar in both groups, the extent of contusional lesion in the PP1 group was reduced by approximately 35% on day 3. Moreover, the water content on days 1, 3, and 7 was significantly reduced and macrophage infiltration on days 3 and 7 was dramatically reduced in the PP1 group. TNF and IL-1beta mRNA expression in the PP1 group were also significantly reduced. These results indicate that PP1 reduces secondary damage after spinal cord injury.

Animals↗

PubMed2004

Improvement of visual acuity caused by opticochiasmal astrocytoma after treatment for associated hydrocephalus--case report.

A 33-year-old male presented with syncopal attacks. He had a history of slowly progressive deterioration of visual acuity in both eyes. His visual deterioration began in the left eye at age 12 years and in the right eye at age 20 years. His left eye was completely blind by age 33 years. He had received no prior treatment for these visual disturbances. Magnetic resonance (MR) imaging on admission showed a large tumor with inhomogeneous intensity occupying the bilateral optic canals and orbital cavities, with extension to parasellar region. Arachnoid cysts were found in the left middle fossa and supracerebellar space, which had caused herniation of the cerebellar tonsils to the foramen magnum. Open biopsy and histology verified that the tumor was pilocytic astrocytoma. Arachnoid cysts associated with the hydrocephalus were treated with a ventriculoperitoneal shunt. Seven years after surgery, visual acuity of the right eye had improved although the left eye remained blind. Follow-up MR imaging demonstrated marked reduction in size of the ventricles and arachnoid cysts, but the tumor size did not change. This case illustrates the benign nature of low-grade glioma in this region in spite of the large size and long history. Deterioration of visual acuity may be reversible in some cases of opticochiasmal astrocytoma. In our case, the improvement in visual acuity probably resulted from growth arrest of the tumor and improvement in the dynamics of cerebrospinal fluid flow.

Adult↗

PubMed2004

Frameless stereotactic surgery using intraoperative high-field magnetic resonance imaging.

This study evaluated the clinical validity of frameless stereotaxy using high-field intraoperative magnetic resonance (iMR) imaging combined with an in-room neuronavigation system. A 1.5 Tesla MR scanner in conjunction with a ceiling-mounted neuronavigation system was used during 32 frameless stereotaxy procedures consisting of 19 brain biopsies and 13 catheter placements between April 2002 and mid-October 2003. Evaluation of the procedure was based on either the rate of histological diagnostic yield or the ability to accurately position the catheter in the target region. This technique allowed successful registration with a mean error of 1.2 +/- 0.8 mm and resulted in successful placement of the instrument within the target tissue. Intraoperatively, frozen section analysis showed all biopsy samples contained pathological tissue and locations of sampling points were confirmed by iMR imaging. Specific final diagnosis was made in all 19 brain biopsies. The tip of the catheter was successfully placed into the target in all 13 patients confirmed by iMR imaging. The catheter was repositioned based on iMR imaging in four of 13 patients, increasing the rate of successful placement. There were no procedure-related neurological deficits or mortality, but we encountered two cases of wound infection, one needing surgical revision. Total additional procedure time related to the induction of iMR imaging was 76.7 +/- 23.3 minutes. This initial experience of the combination of conventional frameless stereotaxy and high-field iMR imaging improved the quality of frameless stereotaxy with low morbidity and mortality, but did not translate into a significant reduction of procedure-related time.

Adolescent↗

PubMed2004

[Three dimensional MRI].

Three-dimensional(3D) MRI is discussed in the present and future clinical application. The newly reconstructed 3D MRI have been widely utilized as a routine examination, and 3D MRA have been substituted for cerebral angiograms in some diseases. The parallel image with multiple phased-array coils can improve time resolution and reduce MRI artifacts. Fusion of 3D anatomical MRI with CT, various functional MRI, SPECT, and PET results in precise diagnosis and improves the accuracy in navigational neurosurgery and stereotactic radiosurgery. High-field 3-tesla MRI can be clinically used, but its role on 3D MRI is not clear. As the data of 3D MRI and multi detector-row CT increases, it becomes the major problem how to restore and protect these data.

Brain Neoplasms↗

PubMed2004

[Intracranial hypovolemic syndrome with subdural hygroma developed massive hematoma: timing of treatment and histology of dural hypertrophy].

We report a case of a 43-year-old man treated by craniotomy for chronical subdural hematoma (CSH) due to spontaneous intracranial hypovolemia. The patient complained of sudden onset severe headache. Initial CT scan showed normal brain structure, and his headache improved with bed rest in a few days. However, MR images obtained for vertigo one month later demonstrated bilateral subdural hygroma extending to the supracerebellar space and diffuse dural enhancement after gadolinium infusion. We diagnosed bilateral subdural hygroma due to spontaneous intracranial hypovolemia, and observed him conservatively. Four months after onset, he complained of severe headache again and MR images revealed enlargement of bilateral CSH with mass effect, which had heterogenous intensity on the right convexity. We evacuated hematoma on the right by craniotomy and aspirated the left side hematoma using a burr hole. His headache improved 2 weeks after the operation with strict bed rest. The follow-up MR images showed disappearance of abnormal meningeal enhancement and improvement of brain sagging.

Adult↗

PubMed2003

Congenital cavernous angioma exhibits a progressive decrease in size after birth.

CASE REPORT: We report a case of congenital intracranial cavernous angioma, which was initially found at a gestational age of 34 weeks in utero as a mass lesion associated with hydrocephalus. After birth, the patient was treated for hydrocephalus first by external drainage and then by ventricular peritoneal shunt. The natural course of the mass lesion was observed until the age of 8 months when the histopathological diagnosis confirmed the cavernous angioma after tissue was obtained by surgery. CT scans repeated monthly during this period demonstrated that the angioma continuously decreased in size. There was no evidence of hemorrhage in the angioma on serial CT scans. The histopathology revealed thrombosis of cavernous vessels with hyaloid changes in the angioma. DISCUSSION: The mechanisms of the decreasing size of the cavernous angioma have often been discussed in relation to spontaneous hemorrhages and resolution. The present case suggests a mechanism in which the spontaneous formation of a thrombus might be the dominant factor for the decrease in size. Thrombus formation may result from low perfusion due to the large size of the angioma.

Brain Neoplasms↗

PubMed2003

Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells.

Aurora-A, a member of the Aurora/Ipl1-related kinase family, is overexpressed in various types of cancer and considered to play critical roles in tumorigenesis. To better understand the pathological effect of Aurora-A activation, it is first necessary to elucidate the physiological functions of Aurora-A. Here, we have investigated the roles of Aurora-A in mitotic progression with the small interfering RNA, antibody microinjection, and time lapse microscopy using human cells. We demonstrated that suppression of Aurora-A by small interfering RNA caused multiple events to fail in mitosis, such as incorrect separation of centriole pairs, misalignment of chromosomes on the metaphase plate, and incomplete cytokinesis. Antibody microinjection of Aurora-A into late G2 cells induced dose-dependent failure in separation of centriole pairs at prophase, indicating that Aurora-A is essential for proper separation of centriole pairs. When we injected anti-Aurora-A antibodies into prometaphase cells that had separated their centriole pairs, chromosomes were severely misaligned on the metaphase plate, indicating that Aurora-A is required for proper movement of chromosomes on the metaphase plate. Furthermore, inhibition of Aurora-A at metaphase by microinjected antibodies prevented cells from completing cytokinesis, suggesting that Aurora-A also has important functions in late mitosis. These results strongly suggest that Aurora-A is essential for many crucial events during mitosis and that the phosphorylation of a series of substrates by Aurora-A at different stages of mitosis may promote diverse critical events in mitosis to maintain chromosome integrity in human cells.

Antibodies↗

PubMed2003

Primary granulocytic sarcoma in the sphenoidal bone and orbit.

CASE REPORT: We report a case of a primary cranial chloroma in boy aged 2 years and 8 months. The symptoms were progressive bilateral exophthalmos, right abducens palsy, and bilateral papilledema. The tumor was partially calcified and was a round mass located in the bilateral sphenoidal bone extending into the orbit. Laboratory study did not show hematological abnormality. The tumor was partially removed by bilateral frontotemporal craniotomy and a diagnosis of primary granulocytic sarcoma was made from the surgical specimen. Progressive deterioration of visual acuity was seen and chemotherapy started on the 11th postoperative day followed by local cranium irradiation (24 Gy). The patient has been in complete remission for 37 months. The visual acuity recovered partially and follow-up magnetic resonance imaging showed a significant decrease in the size of the tumor. DISCUSSION: Radiological diagnosis of primary intracranial granulocytic sarcoma is difficult. Surgical removal may be an option for progressive neurological deterioration but chemotherapy is more important for both neurological stabilization and induction of remission.

Brain Neoplasms↗