Norihiko Tamaki

Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells

Background: Various mitotic events are controlled by Cdc2‐cyclin B and other mitotic kinases. Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a potential oncogene. However, the regulation of aurora‐A activation and the commitment of aurora‐A in the progression of G2‐M phase are largely unknown in mammalian cells.

Cerebral Vasoreactivity and Internal Carotid Artery Flow Help to Identify Patients at Risk for Hyperperfusion After Carotid Endarterectomy

Background and Purpose— Hyperperfusion syndrome is a rare but potentially devastating complication after carotid endarterectomy (CEA). The aim of this study was to investigate whether preoperative measurement of cerebral vasoreactivity (CVR) and intraoperative measurement of internal carotid artery (ICA) flow could identify patients at risk for hyperperfusion after CEA. Methods— For 26 patients with unilateral ICA stenosis ≥70%, cerebral blood flow (CBF) and CVR were investigated before and 1 month after CEA, with resting and acetazolamide-challenge single-photon emission CT. CBF on the first postoperative day was also measured. ICA flow was measured before and after reconstruction by electromagnetic flowmeter during surgery. Results— Ipsilateral CBF on the first postoperative day significantly increased relatively (56.6±53.2%) as well as absolutely (37.9±8.8 to 57.7±18.0 mL/100 g per minute) in the reduced CVR group (CVR <12%) but not in the normal CVR group (CVR ≥12%) (10.3±15.5% and 40.6±7.9 to 43.9±5.7 mL/100 g per minute, respectively). One month later, this difference almost disappeared. Two patients showed ipsilateral CBF increase of ≥100%. A significant association of intracerebral steal with hyperperfusion (CBF increase ≥100%) on the first postoperative day was also observed. ICA flow increase after reconstruction significantly correlated with CBF increase on the first postoperative day in the reduced CVR group but not in the normal CVR group. The threshold of ICA flow increase for hyperperfusion was estimated to be 330 mL/min in the reduced CVR group. Conclusions— Single-photon emission CT with acetazolamide challenge and ICA flow measurement during surgery could identify patients at risk for hyperperfusion after CEA, in whom careful monitoring and control of blood pressure should be initiated even intraoperatively.

Biomechanics of Hydrocephalus: A new theoretical model

The finite element method (FEM), an advanced method of computer simulation, is used to examine biomechanical studies of hydrocephalus. Biots theory of consolidation, which describes the mechanical behavior of a porous medium containing viscous fluid, is applied to represent the coupled behavior of tissue and fluid in the hydrocephalic brain. A computer simulation of the hydrocephalic process is carried out by FEM to evaluate the mathematical model. A two-dimensional finite element model is constructed using a horizontal computed tomographic (CT) slice of the brain. Specifying the material properties of the brain parenchyma, the loading characteristics, and the boundary conditions, the change of interstitial pressure, intracerebral stress distribution, and ventricular configuration are computed and graphically represented. The results of the computer simulation are compared with the findings of CT and magnetic resonance imaging of hydrocephalic patients. The progress of periventricular cerebrospinal fluid edema and ventricular enlargement is well represented by the mathematical model. The model demonstrated that stress concentration in the brain tissue and increased parenchymal hydraulic conductivity play an important role in the generation of periventricular cerebrospinal fluid edema.

Dolichoectatic basilar artery: a review of 23 cases.

The dolichoectatic basilar artery was found in 23 cases during a 10-year period. The 19 males and 4 females ranged in age from 30 to 69 years (mean: 55 years). Hypertension was noted in 17 patients. In seventeen (74%) of the present cases this anomaly could be visualized with CT scan. Seven patients (30%) presented with pontine infarction, which was identified on CT scan in all cases. Vertebro-basilar insufficiency was found in four patients. One patient had transient ischemic attacks. There were facial spasms in four patients and impairment of the lower cranial nerves in one. One patient exhibited cerebellar hemorrhage. In two patients this anomaly was found incidentally. Associated intracranial aneurysms were identified in seven patients, including fusiform aneurysms in 4 and saccular aneurysms in 3. Three patients had an accompanying hydrocephalus. The dolichoectatic basilar artery is associated with various consequences especially in relation to the pathogenesis of brainstem infarction. When this anomaly is diagnosed by CT findings, even if it is clinically asymptomatic, it may be better to treat these patients with medical therapy used to prevent ischemic stroke.

Germ cell tumors of the thalamus and the basal ganglia

Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7–19 years. The clinical course was usually slow. The major symptoms were hemiparesis, mental deterioration such as dementia or character change, precocious puberty, diabetes insipidus, oculomotor palsy, speech disturbance, and hemianopsia. Signs of intracranial hypertension did not occur until the late stages of the disease. The plain CT finding was characterized by an irregularly defined, slightly high-density area frequently accompanied by central low-density areas without significant mass effect. The tumors showed mild to moderate and nonhomogeneous contrast enhancement. An ipsilateral cerebral hemiatrophy was often found. MR images demonstrated the corresponding findings. GCTs of the basal ganglia had a high possibility of containing components other than germinoma such as choriocarcinoma, endodermal sinus tumor, and embryonal carcinoma. Thus, tumor markers in the serum, CSF, or cyst fluid were frequently positive. With recent refinement of microsurgical techniques as well as immunohistochemical study and measurements of tumor markers of serum, CSF, and cyst fluid, major resections of tumor, accurate pretreatment histologic diagnosis, and early determination of the specific types of this tumor appear to be readily possible. This is essential for effective treatment of patients not only with radiosensitive germinoma, but also those with radioinsensitive nongerminoma variants and a combination of them located in this region.

Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase

The critical function of the neurofibromatosis type 1 NF1) gene product (neurofabromin) is not well defined except that neurofibromin has homology with a family of the GTPase‐activating proteins (GAPs). In this study, we confirmed that neuofibromin is constitutively phosphorylated and detected kinase activities which specifically phosphorylated the cysteine/serine‐rich domain and the C‐terminal domain of the neurofibromin in cell lysate. In vitro and in‐gel kinase assays strongly indicated that cAMP‐dependent protein kinase (PKA) is a candidate for the neurofibromin kinase. The biological significance for the phosphorylation of neuofibromin is unclear at present, but we speculate that neurofibromin plays a crucial role in cellular function since it links the two major cellular pathways which are the GAP‐rins and PKA‐associated signals.

The effects of cooling and rewarming on the neuronal activity of pyramidal neurons in guinea pig hippocampal slices

To investigate the reversibility of neuronal functions during deep and mild hypothermia, we have examined changes in membrane properties of pyramidal neurons of the CA3 region of hippocampal slices during cooling and rewarming (8 approximately 37 degrees C) of the perfusion medium. Hypothermia reduced the excitatory postsynaptic potential (EPSP) slope in a temperature dependent manner, but the EPSP amplitude was enhanced transiently between 30 and 25 degrees C. In observing spikes generated by either orthodromic stimulation or by direct intracellular current injection, the critical threshold for spike generation was decreased transiently at a temperature of 30 degrees C. In addition, the numbers of spikes were increased transiently regardless of the progressive prolongation of spike duration and latency with cooling. The resting membrane potential was stable from 37 to 20 degrees C. However, this potential showed a depolarizing shift at 15 degrees C. The neuronal activities, including membrane properties, recovered fully when the temperature was raised to 35 degrees C even from a low of 15 degrees C. In addition, field population spikes (PS) recorded in the pyramidal cell layer showed a complete reversibility after long-term severe hypothermia (8 degrees C). These results suggest that synaptic function, neuronal excitability and membrane properties maintain reversibility during deep hypothermia, as well as in mild hypothermia.

Effective shunt-independent treatment for primary middle fossa arachnoid cyst

The results of a prospective study on excision of the outer and inner membrane for symptomatic primary middle fossa arachnoid cysts in children are presented. During the period 1982–1989, among 48 cases of cyst in various locations, 18 symptomatic patients were treated by excision of both the outer and inner membranes with an opening to the basal cistern. The mean patient age was 3.2 years. All patients were evaluated by examinations, including magnetic resonance imaging (MRI), X-ray computed tomography (CT), quantitative CT cisternography (CTC), digital substraction angiography (DSA), N-isopropyl-p[123]iodoamphetamine single-photon emission CT (IMP-SPECT) and IQ. All showed abnormal cerebrospinal fluid flow dynamics. Significant complications included massive subdural effusion in two patients and transient pulmonary edema in one. There were no recurrences during the follow-up period (mean 4.7 years). Two morphological types were noted: type I, the classical anteromedial type where the cysts are attached directly to the adjacent parasellar cisterns, and type II, the anterolateral type, where the diagonally concave anterior temporal lobe covers the adjacent cisterns, making wide opening difficult. Type I accounted for 78% of all cases, and the reduction of the cyst volume with clinical improvement was remarkable within 6 months after surgery. Angiographically, 22% of cases showed tapering and retrograde filling of the superficial middle cerebral vein. This pattern is not included in Hackers normal variations [18] and suggest mild but chronic compression of the developing brain. Even in patients with hemispheric cyst, the reconstituted brain showed sufficient cerebral perfusion on SPECT, suggesting that the nature of this disease entity is reversible developmental arrest. These results confirm that excision is a safe, effective shunt-independent procedure for middle-fossa arachnoid cysts, especially for those of type I.

Angiographic classification of aneurysms of the horizontal segment of the anterior cerebral artery.

Ten aneurysms of the horizontal portion of the anterior cerebral artery (A1) were analyzed. These 10 aneurysms were classified into three types according to the mode of the origin of the neck of the aneurysm from the A1 segment: (a) an aneurysm originating from the junction of the A1 segment and the lenticulostriate artery, (b) one from the proximal end of the fenestration of the A1, and (c) one from the top of the A1 loop (elongation and kinking of the A1 segment). In these aneurysms, their size, the side of the A1 segment with an aneurysm, the multiplicity of aneurysms, the coexistence of hypertension, the grade of the patients, the laterality of the subarachnoid blood clots (as seen on computed tomography scans) and surgical outcome were analyzed.

Aneurysms of the distal posterior inferior cerebellar artery: experience with three cases and review of the literature.

We report 3 surgically treated aneurysms of the distal posterior inferior cerebellar artery (PICA) and review 36 cases in the literature. More than half of the distal PICA aneurysms arose distal to the choroidal arch. These lesions often arose at a turning point (i.e., a hairpin curve) of an artery instead of at a junction of vessels. Distal PICA aneurysms are likely to be missed and it is necessary to investigate carefully with four-vessel angiography even if computed tomography is done. Eighty-two per cent of the surgically treated 39 patients had good recoveries and 8% had fair results. The mortality rate was 10%. Although clipping of the aneurysm neck is preferable, trapping is useful when neck clipping is impossible in segments distal to the choroidal arch.