Atsuhisa Nakano

Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells

The proteasome inhibitors lactacystin and AcLLNal induced p53‐independent apoptosis in two human glioma cell lines, and the apoptosis was accompanied by up‐regulation of immunoreactive wild‐type p53, p21Waf1, Mdm2, and p27Kip1. Pretreatment with cycloheximide decreased the induction of cell death independently of p53 protein status, suggesting that the up‐regulation of short‐lived proteins is associated with proteasome inhibitor‐induced apoptosis. Caspase‐3‐like proteases were activated in the proteasome inhibitor‐mediated apoptosis, and the induction of cell death was inhibited more effectively in the presence of z‐VAD.fmk than in the presence of Ac‐DEVD.fmk, suggesting that caspases other than caspase‐3 are involved. Nonetheless, there were no significant alterations in levels of immunoreactive Bcl‐2, Bcl‐xL, Bax, Bad, and Bak, nor any evidence of cytochrome c release into cytosol and dissipation of ΔΨ m. Thus, the proteasome inhibitor‐induced apoptosis is mediated by a mitochondria‐independent mechanism, and the once activated caspase‐3 does not cause the cytochrome c release and the ΔΨ m disruption.

Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells

Brain-specific angiogenesis inhibitor 1 (BAI1) is a p53-target gene specifically expressed in the brain. We examined the distribution of the endogenous BAI1 protein in normal human brain tissue using a polyclonal antibody against the extracellular region of BAI1. Immunohistochemical study demonstrated that BAI1 was expressed in neuronal cells of the cerebral cortex but not in astrocytes. BAI1 protein was localized in the cellular cytoplasm and membrane. It was predominantly localized in the cellular membrane when expressed in cultured cells by means of gene transfection. BAI1 protein may play an important role in neuronal functions such as synapse formation and signal transduction.

Cerebrospinal fluid leakage from the nipple after ventriculoperitoneal shunt: Case report

A case of ventriculoperitoneal shunt malfunction is presented, in which cerebrospinal fluid was discharged from the nipple. A pseudocyst was found at the end of peritoneal catheter in the right subphrenic abdominal cavity. In addition, a fibrous tract was formed around the peritoneal catheter and communicated with the lactiferous duct probably injured incidentally during the subcutaneous insertion of catheter. Consequently, cerebrospinal fluid accumulated in the pseudocyst in the abdominal cavity and then flowed backward in the fibrous tract to the lactiferous duct during the respiration to discharge from the nipple.

Immunoblotting of Contractile and Cytoskeletal Proteins of Canine Basilar Artery in Vasospasm

Vasospasm was produced in the canine basilar arteries by a two-hemorrhage method, and voltage- and receptor-dependent contractions of the normal canine basilar arteries were induced by local applications of potassium chloride (KCI) and serotonin, respectively, after transclival exposure. Actin, myosin, desmin, filamin, talin, vinculin, and alpha-actinin in the basilar artery were studied by immunoblotting. The immunoblots showed a decrease or loss in immunoreactivity of some native proteins and generation of protein fragments, smaller in size than native proteins, in spastic, KCI, and serotonin groups, indicating a proteolytic degradation. In the spastic group on Day 2, actin, desmin, and filamin were usually degraded slightly; myosin moderately; and talin and alpha-actinin substantially. Vinculin and metavinculin remained intact. In the spastic group on Day 7, actin and desmin were usually decomposed slightly; myosin, filamin, and vinculin substantially; and talin, metavinculin, and alpha-actinin markedly. In the KCI and serotonin groups, slight degradation was usually observed in filamin, often in alpha-actinin, and occasionally in actin, whereas desmin, vinculin, and metavinculin were not degraded. In addition, myosin was usually degraded moderately in the KCI group and slightly in the serotonin group, and talin was generally decomposed slightly in the KCI group and moderately in the serotonin group. The degraded fragments, although variable in number and immunoreactivity, were similar in size in the three groups. We suggest that the intracellular devices responsible for contraction of the basilar arteries are degraded more severely in the spastic group than in the KCI or serotonin group, probably by similar proteolytic mechanism and progressively with the passage of time after subarachnoid hemorrhage in vasospasm.

Unexpected Delayed Rupture of the Vertebral – Posterior Inferior Cerebellar Artery Aneurysms Following Closed Head Injury

Summary Subarachnoid haemorrhage secondary to closed head injury is rarely associated with traumatic aneurysms of the posterior circulation. We report two cases of ruptured vertebral-posterior inferior cerebellar artery (VA-PICA) pseudoaneurysms following closed head injuries. In each case, there was no associated penetrating injury or skull fracture. The first patient was kicked followed by disturbed consciousness. The computerized tomography (CT) scan on admission and cerebral angiography on the 11th day after the trauma revealed a massive subarachnoid haemorrhage (SAH) with pan-ventricular haemorrhage and an aneurysm of the right PICA near its origin. Further ruptures occurred on the 12th, 15th, and 66th day, and he died on the 69th day. The second patient complained of persistent headache and nausea following a fight on the previous day. A CT scan and angiography on the 1st day after the trauma showed posterior fossa SAH with fourth ventricular blood and a tiny protrusion of the left VA-PICA. On the 14th day, repeated angiography revealed a remarkable growth of the aneurysm, followed by the second rupture. The repair of the VA-PICA junction was urgently performed with successful exclusion of the aneurysm. To our knowledge, only eight cases of traumatic aneurysms located at the VA or the PICA near its origin have been reported. When intraventricular blood is found with massive subarachnoid blood or with posterior fossa SAH, this omnious complication should be considered. Traumatic VA-PICA pseudoaneurysms are curable by refined microsurgical techniques, if diagnosed in time.