Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma.

Retinoic acid (RA) has been shown to induce neuronal differentiation and/or apoptosis, and is widely used as a chemotherapeutic agent for treating the patients with neuroblastoma. However, the therapeutic effect of RA is still limited. To unveil the molecular mechanism(s) inducing differentiation and apoptosis in neuroblastoma cells, we compared CHP134 and NB-39-nu cell lines, in which all-trans-RA (ATRA) induces apoptosis, with LA-N-5 and RTBM1 cell lines, in which it induces neuronal differentiation. Here, we found that Bcl-2 was strongly downregulated in CHP134 and NB-39-nu cells, whereas it was abundantly expressed in LA-N-5 and RTBM1 cells. ATRA-mediated apoptosis in CHP134 and NB-39-nu cells was associated with a significant activation of caspase-9 and caspase-3 as well as cytoplasmic release of cytochrome c from mitochondria in a p53-independent manner. Enforced expression of Bcl-2 significantly inhibited ATRA-mediated apoptosis in CHP134 cells. In addition, treatment of RTBM1 cells with a Bcl-2 inhibitor, HA14-1, enhanced apoptotic response induced by ATRA. Of note, two out of 10 sporadic neuroblastomas expressed bcl-2 at undetectable levels and underwent cell death in response to ATRA in primary cultures. Thus, our present results suggest that overexpression of Bcl-2 is one of the key mechanisms to give neuroblastoma cells the resistance against ATRA-mediated apoptosis. This may provide a new therapeutic strategy against the ATRA-resistant and aggressive neuroblastomas by combining treatment with ATRA and a Bcl-2 inhibitor.

Evaluation of the analgesic effects of capsaicin using a new rat model for tonic pain.

An animal model for tonic pain has been produced by means of injecting monosodium urate crystals into a knee joint of rat hind paws in order to evaluate the analgesic effects of various drugs and analgesic methods and to elucidate the physiology of tonic pain. This model allows for stable and long-term behavioural changes due to tonic pain followed by complete recovery without tissue damages. It is advantageous in allowing for objective and quantitative evaluation of the effects of analgesics and should prove useful in research on pain and the development of pain therapy techniques. Using this model, the analgesic effects of capsaicin was evaluated when administered to the neonatal rat or locally to peripheral nerves. In both cases, significant analgesic effects were obtained.

Stereotactic aspiration of putaminal hemorrhage using a double track aspiration technique.

Double track aspiration was used to remove the hematoma between 6 and 24 hours from onset in nine cases of putaminal hemorrhage. This technique was used in cases where an approach along the long axis of the hematoma was not feasible. With this method, aspiration is done at two target points lying anterior and posterior of the somewhat harder central region, at which aspiration is not attempted. This technique allows aspiration of most of the serum components, which are depicted as low density areas in computed tomographic (CT) scans, and some 53 to 85% of the main mass of the hematoma, which is seen on CT as high density areas. There was no rebleeding among these nine patients, and the remaining hematoma in all cases was located between two target points--a fact that is thought to indicate that the central portion of the hematoma is in fact somewhat harder than the peripheral portions. Although the double track aspiration technique has the disadvantage of producing two tracks, it is thought to be an effective method in such cases because it allows safe and thorough hematoma aspiration.

Computed tomography-guided stereotactic aspiration of posterior fossa hematomas: a supine lateral retromastoid approach.

We report a supine lateral retromastoid approach for computed tomography-guided stereotactic aspiration of hematomas of the posterior fossa. The method involves horizontal insertion of the aspiration needle at the suboccipital region with the patient in a supine position with the head turned 30 to 40 degrees away from the lesion and with slight forward flexion of the neck. Eleven hematomas have been removed through this approach thus far, nine cerebellar and two pontine. With this technique, general anesthesia is not needed and operative invasion is minimal, allowing hematoma aspiration in patients in whom operation would previously not have been indicated. An additional merit is the suitability of this method for elderly patients.

Trigeminal neurinoma associated with suprasellar arachnoid cyst: case report.

The first case of trigeminal neurinoma associated with suprasellar arachnoid cyst is presented. Coexistence of these two lesions may be accidental, but it is also possible that the arachnoid cyst was secondary to the neurinoma.

Results of stereotactic aspiration in 175 cases of putaminal hemorrhage.

Believing that improved therapeutic results in cases of intracerebral hematoma might be obtained by minimal invasion of the brain, we used computed tomographic-guided stereotactic aspiration in 175 of 241 patients with putaminal hemorrhage. These patients, who were treated 6 or more hours after onset, had hematomas larger than 8 ml and were unable to raise an arm and/or leg on the affected side. Craniotomy was performed in 15 other patients, most of whom were brought to the hospital with large hematomas within 6 hours of onset. The remaining patients either had mild deficits of consciousness (33 patients) or severe deficits and/or were elderly (18 patients) and were treated conservatively. Thirteen patients (7.4%) showed rebleeding after stereotactic aspiration (6 instances of major and 7 instances of minor rebleeding). Craniotomy and removal of the hematoma were required in three of these patients. Aspiration should be avoided in patients who have a tendency for bleeding, even if mild, because rebleeding occurred in 6 of 23 such patients (26%) in these study. The consciousness level improved in 66 patients (38%), was unchanged in 103 patients (59%), and was worse in 6 patients (3%) 1 week postoperatively. Motor function of the arm improved in 55 patients (31%) and was worse in 23 patients (14%). Six months after surgery, the results for the 175 patients who underwent stereotactic aspiration were: 19% excellent, 32% good, 35% fair, 7% poor, 6% dead, and 1% unknown. For the entire series of 241 patients, the results were: 24% excellent, 26% good, 31% fair, 7% poor, 11% dead, and 1% unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Anterior communicating artery aneurysms with associated anomalies.

In 296 cases with a single aneurysm of the anterior communicating artery (ACoA), fenestration or the presence of more than two ACoA's was observed in 17 cases (5.7%), and abnormal vessels of ACoA origin, such as a median artery of the corpus callosum, were observed in 13 cases (4.4%). As more than one anomaly was found in some of these cases, anomalies of the ACoA were found in total of 26 cases (8.8%). This occurrence rate was no higher than that observed in other cerebral aneurysm cases and in the control cases, which were reported previously. There was no significant increase of hypoplasia of the A1 portion if the ACoA aneurysm was complicated by other arterial anomalies.

Experimental retrograde adriamycin trigeminal sensory ganglionectomy.

Direct destruction of the sensory ganglion or its root, by either surgical transection or injection of phenol, has been employed as preferred treatment for a variety of neuralgic pain syndromes. In this report, the suicide axoplasmic transport of adriamycin is described as a novel approach to sensory ganglionectomy. When injected into a branch of the trigeminal nerve in the cat, adriamycin was swiftly transported by way of retrograde axoplasmic flow to the sensory neurons parental to the injected nerve, where adriamycin-specific autofluorescence was observed. Trigeminal sensory evoked potentials became unobtainable 24 to 48 hours after injection of adriamycin in concentrations of 1% to 10%. The sensory neurons underwent subacute degeneration within a week due to the delayed action of adriamycin, and consequently the primary afferents degenerated in a restricted projection field of the brain-stem trigeminal sensory nuclei. These results indicate that retrograde axoplasmic transport of adriamycin is a unique approach to noninvasive sensory ganglionectomy with strict, albeit simple, safe targeting of sensory neurons and little likelihood of regeneration.

The development and morphogenesis of the human pituitary gland.

In order to clarify the environmental factors which are involved in the development of the primordium of the pituitary gland such as cell-cell interactions, a three-dimensional reconstruction of this organ and its surrounding tissues was carried out. Pituitary material was obtained from human fetuses mainly during the period of organogenesis. Rathke's diverticulum was found to stretch rostrally from the stomodeal epithelium to the middle of the mesoderm, and already by the 5th week of fetal growth, it was clearly seen to be involved with the diencephalon. The area of contact between Rathke's pouch and the diencephalon gradually moved from the rostral to caudal regions and, after 13 weeks of development, had a position similar to that found in the newborn infant. Among the cells forming Rathke's pouch, it was found that the closer their relationship was to the diencephalon, the greater were their epithelial characteristics. When the relationship of such cells to the diencephalon was weaker, their differentiation to endocrine cells occurred earlier. Immunohistochemically, that portion of the pituitary primordium which has a close relationship with the diencephalon, later to become the pars intermedia, showed an adrenocorticotropic hormone (ACTH) immunoreactivity later than that of the pars anterior. On the other hand, in the 21st fetal week, nearly all of the cells of the pars intermedia were found to be ACTH-positive. This finding is thought to indicate a close connection between the physical contact between the brain (diencephalon) and the pituitary primordium and the development of the pars intermedia; the differentiation of ACTH cells. The surface of the epithelium of Rathke's cavity continues to increase at least until the 21st fetal week, so the growth of the epithelium of Rathke's pouch is thought to be heavily involved in the growth of the primordium of the pituitary gland in the early stages of development.

Paroxysmal speech disorder following left frontal brain damage.

The patient was a 61-year-old female who suffered from the sudden attack of a speech disorder. The episodes of speech disorder lasted for less than 1 min, but occurred several times a day, paroxysmally. A CT revealed a low density area on the surface of the left frontal lobe and an EEG showed an abnormal wave at the frontoparietal area, more dominantly on the left. This condition was diagnosed as a kind of epilepsy. The paroxysmal speech disorder occurred very often during the 2 months after the first episode. However, with therapy using anticonvulsives and antibiotics, the condition began to improve after 4 months and disappeared completely after 6 months. It is assumed that the inflammatory change which occurred at the frontal lobe stimulated the supplementary motor area paroxysmally, and subsequently the speech disorder occurred as a kind of epilepsy.

Aneurysmal bone cyst of the skull.

A case of a 48-year-old woman with aneurysmal bone cyst of the skull is reported. By using estrogen, which is one of the chemical embolizing agents, the abnormal vascular shadow disappeared and clinical symptoms were improved. The significance of selective external carotid angiography in the diagnosis of this lesion is discussed and the benefit of this therapeutic method is argued.

Afferent artery and the site of neck of anterior communicating aneurysms.

The relationship between the afferent artery and the site of aneurysmal neck and hemodynamics in the anterior part of the circle of Willis was investigated from surgical and angiographic findings in 213 patients with anterior communicating artery aneurysms. An afferent artery was limited to the dominant A1 in about 95% of them. The neck of an aneurysm was more than three times greater at the bifurcation of the dominant A1 and the anterior communicating artery than at the bifurcation of the non-dominant A1 and the anterior communicating artery.

Angiographic study of cerebral vasospasm following rupture of intracranial aneurysms: Part I. Time of the appearance.

An investigation of the time of appearance of vasospasm as seen angiographically after the onset of subarachnoid hemorrhage was carried out on 797 cases of intracranial saccular aneurysm in which operations were performed. It has been reported that vasospasm often occurs early after the onset of subarachnoid hemorrhage. With only one subarachnoid hemorrhage, vasospasm occurred within three days after the hemorrhage in only 4.2% of the 120 cases in this study. The appearance of vasospasm was most frequently seen angiographically between ten and 17 days. During this period vasospasm was seen in 49.1% of 116 cases. In those cases with a subarachnoid hemorrhage one to 17 days before the last one, vasospasm within three days after the last hemorrhage was seen in 38.7% of 62 cases. During the period between ten and 17 days after the last hemorrhage, vasospasm was seen in only 20% of 25 cases. The preceding subarachnoid hemorrhage, which had occurred between one and 17 days before the last hemorrhage, seemed to be responsible for the high rate of vasospasm within three days after the last hemorrhage, and the low rate of vasospasm in the period between ten and 17 days after the last hemorrhage.

Angiography study of cerebral vasospasm following the rupture of intracranial aneurysms: Part II. Relation between the site of aneurysm and the occurrence of the vasospasm.

The relation between the occurrence of vasospasm and the site of ruptured aneurysm was investigated. Vasospasm tended to occur initially on arteries close to the aneurysm, later extending to other locations. Contralateral spasm was more frequent the closer the site of the aneurysm to the mid-sagittal line. The spasm observed angiographically varies in relation to the site of the aneurysm; the site of the hematoma in the subarachnoid space was supposed to be the cause of such variation.

Acoustic neurinoma presenting as subarachnoid hemorrhage.

A 49-year-old man who had been suffering from disturbance of hearing for 5 years suddenly developed severe headache, nausea, and vomiting. Computed tomography (CT) scans both with and without contrast medium enhancement, performed on the day of admission, showed a nearly round high-density area in the left cerebellopontine angle. A left transaxillary vertebral angiogram showed no aneurysm or arteriovenous malformation. Hemorrhage from a tumor in the left cerebellopontine angle was suspected. CT scan without contrast medium enhancement, performed on the 17th day after onset, showed only a small, ill-defined high-density area in the cerebellopontine angle. An operation was performed on the 20th day after onset. The tumor was totally extirpated together with a clot. Histologically the tumor was an acoustic neurinoma with hemorrhage and necrosis. The postoperative course was favorable. Massive hemorrhage from primary intracranial tumors, especially acoustic neurinomas, is discussed. Radical operation on the tumor should be performed as soon as possible.

Intracerebral hemorrhage from a metastatic brain tumor. Importance of differential diagnosis preceding stereotaxic hematoma aspiration.

Three cases of sudden intracerebral hemorrhage, which were diagnosed as hemorrhage from metastatic brain tumors following stereotaxic aspiration of a hematoma, are reported. Two cases had subcortical hemorrhage and one had cerebellar hemorrhage. Neither contrast-enhanced computed tomography scans nor angiograms revealed any findings other than those indicating the hematoma in all three cases. However, retrospective study of the anamnesis showed very mild symptoms due to metastasis to the brain or spinal cord in one case each. In cases of intracerebral hematoma located at atypical sites, extreme care is required for the differential diagnosis.

Hepatitis C virus (HCV) infection as a risk factor for spontaneous intracerebral hemorrhage: hospital based case-control study.

Hepatitis C Virus (HCV) infection was investigated as a risk factor for intracerebral hemorrhage (ICH) by HCV antibody screening in 462 patients with ICH and 462 control patients with cerebral infarction matched by age and sex. Laboratory examinations of hemostatic parameters and cholesterol level were also performed in patients with ICH. HCV infection was significantly more frequent in patients with ICH than controls (8.7% vs 3.5%, P< 0.01). ICH patients with HCV infection had significantly higher L-alanine:2-oxoglutarate aminotransferase level (P< 0.001), lower cholesterol level (P< 0.05), lower platelet count (P< 0.05), and longer prothrombin time (P< 0.01) than ICH patients without HCV infection, although most of these values were within the normal range. These results demonstrate that HCV infection is a risk factor for spontaneous ICH. Subclinical clotting disorder and/or vessel wall friability resulting from hypocholesteremia may be associated with ICH in patients with HCV infection.

[CT-guided stereotaxic implantation of a deep brain electrode for the stimulation of the internal capsule--a case report].

A 47-year-old man was admitted to our clinic because of the pain of left extremities for four years. The patient developed dysesthesia, hyperpathia and spontaneous pain 2 months after the onset of cerebrovascular accident with left hemiparesis. Using Toshiba TCT-20A CT scanner and Leksell's CT-stereotaxic system, stimulation electrode (by Medtronic Co.) was implanted in the posterior limb of the internal capsule which was 25 mm lateral to the posterior commissure. Ventriculography was not necessary because the target point was directly measured from the axial CT and midsagittal reformatted CT based on 18 axial CT images (2 mm thick slices). Anterior commissure, pineal calcification, posterior commissure and Sylvian aqueduct were demonstrated on the midsagittal reformatted CT by this method. The pain was relieved by the ramped square pulse stimulation (2 V, 0.6 msec, 50 Hz) and receivor system was internalized. The patient was free from pain by 30 minutes-long stimulation four to six times a day. Precise electrode placement was possible by CT images alone using high resolution CT and CT-stereotaxic system. CT-guided stereotaxic technique seemed to have an advantages especially for the implantation of electrode in the posterior limb of the internal capsule. The reason is as follows: The target is just lateral to the posterior commissure which could be recognized easily on the midsagittal reformatted CT. The internal capsule is advantageously demonstrated on the axial CT.

[Trigeminal neuralgia and hemifacial spasm caused by the compression of tortuous vertebro-basilar system--a case report (author's transl)].

A 63-year-old man was admitted to our clinic on August 14, 1980 with the chief compliant of left-sided intermittent facial pain. He had been suffering from twitching of the left facial muscles since 1972. During two years before admission, severe pain of the left face, starting in the left upper jaw and radiating to the left periorbital region, occurred intermittently. The pain aggravated by eating, talking and face-washing, gradually worsened and he became unable to take meals. On admission, he was alert. No sensory disturbance was seen. Muscle twitching was seen in the left orbicularis oculi, orbicularis oris and sometimes in the platysma. Mild facial palsy was recognized on the left side and other cranial nerves were intact. Computed tomogram with contrast enhancement revealed shift of the basilar artery to the left side. Markedly enlarged and tortuous vertebrobasilar system kinking at the left cerebello-pontine angle, was seen on the left vertebral angiogram. This tortuous vertebrobasilar system was presumed to be the cause of the trigeminal neuralgia and hemifacial spasm. The neuralgia disappeared after a controlled thermocoagulation of the left Gesserian ganglion, and the frequency of hemifacial spasm was reduced too. He was discharged with mild hemifacial spasm. The combination of trigeminal neuralgia and hemifacial spasm caused by direct compression of tortuous vertebro-basilar system on the nerve roots is rare. A case was reported and the literature were reviewed.

[Two cases of azygos anterior cerebral artery aneurysm (author's transl)].

Two cases with azygos anterior cerebral artery were reported from an analysis of 37 cases of distal anterior cerebral artery aneurysm. Case 1 was a 57-year-old woman. She had an attack of subarachnoid hemorrhage two months before admission to our clinic. The anterior cerebral artery was not demonstrated on the right carotid angiogram, and an azygos anterior cerebral artery was visualized on the left carotid angiogram. The aneurysm was situated at the distal end of the azygos artery. Case 2 was a 71-year-old hypertensive woman. Subarachnoid hemorrhage occurred 6 days before admission to our clinic. The left carotid angiography with contraleteral compression revealed an azygos artery and an aneurysm in its middle part. The azygos arteries in both cases were confirmed at operation and aneurysmal necks were managed without any serious deficit. The distal anterior cerebral artery aneurysm is frequently accompanied by azygos artery. This vascular anomaly may cause a hemodynamic change and may be one of the factors of aneurysmal formation at this part.