Rtf1-mediated eukaryotic site-specific replication termination.

The molecular mechanisms mediating eukaryotic replication termination and pausing remain largely unknown. Here we present the molecular characterization of Rtf1 that mediates site-specific replication termination at the polar Schizosaccharomyces pombe barrier RTS1. We show that Rtf1 possesses two chimeric myb/SANT domains: one is able to interact with the repeated motifs encoded by the RTS1 element as well as the elements enhancer region, while the other shows only a weak DNA binding activity. In addition we show that the C-terminal tail of Rtf1 mediates self-interaction, and deletion of this tail has a dominant phenotype. Finally, we identify a point mutation in Rtf1 domain I that converts the RTS1 element into a replication barrier of the opposite polarity. Together our data establish that multiple protein DNA and protein-protein interactions between Rtf1 molecules and both the repeated motifs and the enhancer region of RTS1 are required for site-specific termination at the RTS1 element.

Endovascular treatment for dural arteriovenous fistula of the anterior condylar confluence involving the anterior condylar vein. A report of two cases.

SUMMARY: Anterior condylar confluence (ACC) dural arteriovenous fistula (AVF) is a rare anomaly. We describe two cases of ACC dural AVF involving the anterior condylar vein that were successfully treated with selective transvenous coil embolization. The first patient presented with headache and right pulse-synchronous tinnitus, and demonstrated abnormal flow medial to the jugular bulb within the right hypoglossal canal on source image of magnetic resonance angiography (MRA). Arterioangiography disclosed a dural AVF in this area, supplied mainly by the meningeal branches of the bilateral ascending pharyngeal artery. We diagnosed ACC dural AVF involving the anterior condylar vein and transvenous embolization was successfully performed. The second patient presented with right pulse-synchronous tinnitus. Views of source image of MRA and arterioangiography were similar to the first case and, again, transvenous embolization was successfully performed. ACC dural AVF is a rare condition and knowledge of the anatomy of the venous system around the craniocervical junction is required for successful treatment.

A modified burr-hole method in galeoduroencephalosynangiosis for an adult patient with probable moyamoya disease--case report and review of the literature.

A 49-year-old woman with probable moyamoya disease was surgically treated by combined direct and indirect methods, superficial temporal to middle cerebral artery anastomosis and galeoduroencephalosynangiosis by a burr-hole method developed by Kawamoto et al. Transient ischemic attacks and motor weakness of bilateral lower extremities disappeared completely within 1 month and never recurred during 1-year follow-up. Galeoduroencephalosynangiosis by a burr-hole method appears useful for preventing ischemic damage of the territory of the anterior cerebral artery in adult patients with probable moyamoya disease.

Defective plasmid partition in ftsH mutants of Escherichia coli.

FtsH is an ATP-dependent protease that is essential for cell viability in Escherichia coli. The essential function of FtsH is to maintain the proper balance of biosynthesis of major membrane components, lipopolysaccharide and phospholipids. F plasmid uses a partitioning system and is localized at specific cell positions, which may be related to the cell envelope, to ensure accurate partitioning. We have examined the effects of ftsH mutations on the maintenance of a mini-F plasmid, and have found that temperature-sensitive ftsH mutants are defective in mini-F plasmid partition, but not replication, at permissive temperature for cell growth. A significant fraction of replicated plasmid molecules tend to localize close together on one side of the cell, which may result in failure to pass the plasmid to one of the two daughter cells upon cell division. By contrast, an ftsH null mutant carrying the suppressor mutation sfhC did not affect partitioning of the plasmid. The sfhC mutation also suppressed defective maintenance in temperature-sensitive ftsH mutants. Using this new phenotype caused by ftsH mutations, we also isolated a new temperature-sensitive ftsH mutant. Mutations in ftsH cause an increase in the lipopolysaccharide/ phospholipid ratio due to stabilization of the lpxC gene product, which is involved in lipopolysaccharide synthesis and is a substrate for proteolysis by the FtsH protease. It is likely that altered membrane structure affects the localization or activity of a putative plasmid partitioning apparatus located at positions equivalent to 1/4 and 3/4 of the cell length.

Trends in incidence and case fatality rates of aneurysmal subarachnoid hemorrhage in Izumo City, Japan, between 1980-1989 and 1990-1998.

BACKGROUND AND PURPOSE: With aging of the population, the profile of subarachnoid hemorrhage (SAH) is likely to change; however, evaluation of long-term trends for incidence and case fatality rates of SAH is still limited. METHODS: We compared the incidence and case fatality rates of aneurysmal SAH during the 9-year period 1990-1998 with those during the 10-year period 1980-1989 in Izumo City, Japan. RESULTS: During 1980-1989 and 1990-1998, we diagnosed 170 and 188 patients as having aneurysmal SAH, respectively. The percentage of very elderly patients aged >/=80 years increased from 5% (8 patients) during 1980-1989 to 18% (33 patients) during 1990-1998 (P<0.001). The age-specific incidence rate of SAH has a tendency to increase with increasing age. The crude and the age- and sex-adjusted incidence rates using the 1995 population statistics for Japan were 21 and 23 per 100 000/y for all ages during 1980-1989 and 25 and 23 per 100 000/y during 1990-1998, respectively. The 3-month case fatality rate of patients aged /=80 years were very high (63% and 79%, respectively) regardless of study periods. Consequently, the overall case fatality rates for patients with SAH were similar for the 2 study periods (39% and 36%). CONCLUSIONS: The age- and sex-adjusted incidence rates of aneurysmal SAH were stable over the 19-year period since 1980 and, despite improvement of outcome in patients aged

[Dissecting aneurysm of the anterior cerebral artery with persistent pearl & string sign on cerebral angiograms over a period of eight years].

We present a rare case of a dissecting aneurysm of the left anterior cerebral artery (ACA) with persistent pearl & string sign on cerebral angiograms over a period of 8 years. A 43-year-old woman with disturbance of consciousness and right sided hemiparesis was conservatively treated. Computed tomographic (CT) scan revealed a low-density area in the left frontal lobe. Initial angiography, which was performed at 6 months after the onset, showed a pearl & string sign at the A2 portion of the left ACA. After 8 years, repeat angiography again showed persistent pearl & string sign at the same portion of the left ACA. We discussed the changes in findings usually obtained in cerebral angiography concerning dissecting aneurysms in ACA.

Primary intracerebral and aneurysmal subarachnoid hemorrhage in Izumo City, Japan. Part I: incidence and seasonal and diurnal variations.

OBJECT: The purpose of this community-based study was first to estimate the incidence rates of primary intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH) in Izumo City, Japan, and second to investigate whether there were seasonal and diurnal periodicities in their onset. METHODS: During 1991 through 1996, 267 patients with primary ICH and 123 with aneurysmal SAH were treated in Izumo City. The crude and the age- and sex-adjusted annual incidence rates per 100,000 population for all ages were 52 and 48 for ICH and 24 and 23 for SAH, respectively. These incidence rates were higher than those previously published for any other geographical region. The incidence rates of both ICH and SAH increased almost linearly with age. For ICH, a significant seasonal pattern was observed in men and in patients younger than 65 years, with a peak in winter and a trough in summer. However, no significant seasonal fluctuation was found in women or in individuals aged 65 years or older. There was no significant seasonal periodicity for SAH, even when patients were analyzed according to sex and age. Diurnal variations in the onset of both ICH and SAH were significant (except in men with SAH), with a nadir between midnight and 6:00 a.m. CONCLUSIONS: The actual incidence rates of both primary ICH and aneurysmal SAH seem to be much higher than have been reported so far. In addition, the data indicate the existence of seasonal periodicity for men and younger patients with ICH, and that the risk of both ICH and SAH is lower during nighttime.

Primary intracerebral and aneurysmal subarachnoid hemorrhage in Izumo City, Japan. Part II: management and surgical outcome.

OBJECT: The purpose of this study was to assess the overall management and surgical outcome of primary intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH) among the 85,000 residents of Izumo City, Japan. METHODS: During 1991 through 1996, 267 patients with ICH and 123 with SAH were treated in Izumo. Of the 267 patients with ICH, 25 underwent hematoma removal by open craniotomy or suboccipital craniectomy and 34 underwent stereotactic evacuation of the hematoma, whereas aneurysm clipping was performed in 71 of the 123 patients with SAH; operability rates were thus 22% for ICH and 58% for SAH (p < 0.0001). The overall 30-day survival rates were 86% for ICH and 66% for SAH (p < 0.0001) and the 2-year survival rates were 73% and 62% (p = 0.0207), respectively. In patients who underwent surgery, 30-day and 2-year survival rates were 93% for ICH and 100% for SAH (p = 0.0262), and 75% for ICH and 97% for SAH (p = 0.0002), respectively. In patients with ICH, the most important predictors of 30-day case-fatality rates were the volume of the hematoma, the Glasgow Coma Scale (GCS) score, rebleeding, and midline shifting, whereas those for 2-year survival were the GCS score, age, rebleeding, and hematoma volume. In patients with SAH, the most important determinants of 30-day case-fatality rates were the GCS score and age, whereas only the GCS score had a significant impact on 2-year survival. CONCLUSIONS: The overall survival rates for patients with ICH or SAH in Izumo were more favorable than those in previously published epidemiological studies. However, despite improved surgical results, the overall management of ICH and SAH still produced an unsatisfactory outcome, mainly because of primary brain damage.

Chronic hydrocephalus in elderly patients following subarachnoid hemorrhage.

BACKGROUND: With the aging of the population, surgery for ruptured intracranial aneurysms is increasing among the elderly. We sought to clarify the characteristics of chronic hydrocephalus following aneurysmal subarachnoid hemorrhage (SAH) in elderly patients. METHODS: Of the 576 surgically treated patients, 289 were aged 59 years or younger, 169 were 60 to 69, and 118 were 70 years or older. The relationship between chronic hydrocephalus and the causative factors was analyzed for each age group. RESULTS: Of the 576 patients, chronic hydrocephalus was observed in 215 (37%), with the incidence increasing significantly with age (p < 0.001) and being the highest in the oldest age group. In elderly patients, the incidence of chronic hydrocephalus was relatively high, even after mild SAH. The incidence of chronic hydrocephalus was high regardless of age in patients with severe SAH, such as in those with H&H grades III-IV, SAH grades III-IV, acute hydrocephalus, symptomatic vasospasm, and intraventricular hemorrhage, and in those with vertebro-basilar artery aneurysms. CONCLUSION: In the elderly, the incidence of chronic hydrocephalus following SAH was significantly higher than in younger patients, even after mild SAH. In elderly patients, careful observation and individualized treatment are necessary even if SAH is mild.

[Two cases with coil embolization following incomplete neck clipping].

We report two cases with embolization (coil embolization) using Guglielumi detachable coils of residual aneurysms following incomplete neck clipping. The first case, a 75-year-old woman suffered from a subarachnoid hemorrhage due to the rupture of a left internal carotid posterior communicating aneurysm in June, 1997. Neck clipping of the aneurysm was performed at day 1. Follow-up angiogram at day 7 showed a residual aneurysm involving the dome of the initial aneurysm. We performed coil embolization of the residual aneurysm following the angiogram. Almost complete obliteration of the aneurysm lasted during the follow-up period of two and a half years. The second case, a 71-year-old woman suffered from a subarachnoid hemorrhage due to the rupture of a right internal carotid posterior communicating aneurysm in May, 1999. Neck clipping of the aneurysm was performed at day 1. Follow-up angiogram at day 7 showed a residual aneurysm involving only a part of the initial aneurysm near the neck. Because no spontaneous thrombosis of the residual aneurysm was obtained after 2 months, we performed coil embolization of the residual aneurysm. Almost complete obliteration of the aneurysm lasted during the follow-up period of 7 months. These patients were discharged with good performance status. We consider the morphologic feature of the residural aneurysm to be most important for determining when to perform coil embolization of such residual aneurysms.

Dissecting the role of a conserved motif (the second region of homology) in the AAA family of ATPases. Site-directed mutagenesis of the ATP-dependent protease FtsH.

Escherichia coli FtsH is an ATP-dependent protease that belongs to the AAA protein family. The second region of homology (SRH) is a highly conserved motif among AAA family members and distinguishes these proteins in part from the wider family of Walker-type ATPases. Despite its conservation across the AAA family of proteins, very little is known concerning the function of the SRH. To address this question, we introduced point mutations systematically into the SRH of FtsH and studied the activities of the mutant proteins. Highly conserved amino acid residues within the SRH were found to be critical for the function of FtsH, with mutations at these positions leading to decreased or abolished ATPase activity. The effects of the mutations on the protease activity of FtsH correlated strikingly with their effects on the ATPase activity. The ATPase-deficient SRH mutants underwent an ATP-induced conformational change similar to wild type FtsH, suggesting an important role for the SRH in ATP hydrolysis but not ATP binding. Analysis of the data in the light of the crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein suggests a plausible mechanism of ATP hydrolysis by the AAA ATPases, which invokes an intermolecular catalytic role for the SRH.

Dissection from fundus to neck for ruptured anterior and middle cerebral artery aneurysms at the acute surgery.

It is generally believed that a ruptured aneurysm should be dissected from its neck to its fundus or that only the neck should be dissected. This study was conducted to clarify whether, during the acute stage, intra-operative bleeding occurs at the same site as the initial rupture point when aneurysms are dissected completely without clipping. The subjects were 170 patients with ruptured anterior or middle cerebral artery aneurysms who were surgically treated by day 7. These aneurysms were operated on through an interhemispheric or a pterional route, respectively. Most of the aneurysms were dissected from the fundus to the neck. Complete exposure of entire aneurysms without temporary clipping was performed in 118 of 170 patients (69%). Intra-operative aneurysmal rupture occurred during 16 (9%) operative procedures. There were no significant correlations between the rate of intra-operative aneurysmal rupture occurrence and the timing of the operation, pre-operative grade or location of ruptured aneurysms. Intra-operative aneurysmal rupture occurred during dissection of the aneurysm itself in 8 patients, during dissection of the artery adhering to the aneurysm in 5 and during clip application in 3. In all the patients whose aneurysms ruptured during aneurysmal dissection, the rupture was caused by injury to the aneurysm and was not directly related to complete exposure of the aneurysm. Intra-operative bleeding did not occur at the same site as the initial rupture point even when the entire aneurysmal complex was dissected from the fundus to the neck without clipping.

Ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate: case report.

OBJECTIVE AND IMPORTANCE: We report a rare case of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. CLINICAL PRESENTATION: A 44-year-old woman had undergone microvascular decompression for a right-sided facial spasm. The preoperative vertebral angiogram did not show any aneurysmal dilation. The right anteroinferior cerebellar artery, which was compressing the exit zone of the facial nerve, was detached and fixed to the dura mater with ethyl 2-cyanoacrylate. Nine years later, the patient suffered a subarachnoid hemorrhage caused by the rupture of a newly developed aneurysm of the right anteroinferior cerebellar artery. INTERVENTION: The aneurysm was clipped 2 days after onset of the subarachnoid hemorrhage. It consisted of two bulges in the arterial wall on the proximal side of the meatal loop. One bulge was stuck to the dura mater of the pyramis by ethyl 2-cyanoacrylate, which had been used in the microvascular decompression 9 years previously. CONCLUSION: This is the first reported clinical case of a de novo aneurysm induced by a cyanoacrylate adhesive. Ethyl 2-cyanoacrylate can damage the arterial wall and induce a de novo aneurysm.

What are the actual incidence and mortality rates of subarachnoid hemorrhage?

BACKGROUND: From 1987-92 in Izumo City, Japan, we diagnosed 123 patients as having subarachnoid hemorrhage (SAH) by computed tomography, autopsy, or surgery (proven SAH); the crude incidence rate was 25/100,000/year for all ages. However, to estimate the actual incidence and mortality rates, we should take into account the decedents who died without confirmation by these methods but were presumed to have died of SAH. METHODS: From 1987-92, we reviewed all of 3562 death certificates for the city of Izumo (population 82,679), and calculated the incidence and mortality rates of SAH by combining proven and possible SAH. RESULTS: We diagnosed 36 patients as having possible SAH on death certificates. When adding these 36 patients to the 123 with proven SAH, the crude and the age-adjusted and sex-adjusted incidence rates for all ages became 32/ 100,000/year and 29/100,000/year, respectively. Of these, 40% (64) died by day 3 (day 0 defined as the day of hemorrhage), 43% (69) within 1 week, and 53% (84) within 1-6 months, respectively. CONCLUSIONS: When including the patients who may have died of SAH, the actual incidence rate of SAH is much higher than that which has been reported to date, and the actual mortality rate is still very high.

5'-linked lipid-oligodeoxyridonucleotide derivatives as inhibitors of human immunodeficiency virus replication.

The covalent attachment of a phospholipid moiety, bound to the 5'-ends of phosphodiester and phosphorothioate oligonucleotides (L-ODNs and LS-ODNs), was achieved using H-phosphonate chemistry, and the lipid-oligonucleotides were assayed for the inhibition of virus replication in HIV-1 infected MT-4 cells. In the anti-HIV activity test, lipid-phosphorothioate oligonucleotides showed higher anti-HIV activities than non-lipid-phosphorothioate oligonucleotides, at the low concentration of 0.04 microM. LS-ODNs can inhibit HIV-1 reverse transcriptase activity through interactions with the enzyme. We found that the covalent attachment of a phospholipid group to the 5'-end of the phosphorothioate oligonucleotide enhances its nonsequence specific anti-HIV activity.

[A case of multiple cerebral arteriovenous malformations treated by gamma knife radiosurgery].

We reported a case of multiple cerebral arteriovenous malformations (AVMs) treated by gamma knife radiosurgery. A 6-year-old girl was admitted because of systemic tonic convulsion. At the first admission, we performed only vertebral angiography, which showed a 15 mm cerebral AVM. It was fed by the right posterior cerebral artery and drained into the great vein of Galen. Seven years after the first admission, the patient returned again with severe headache. Four-vessel cerebral angiograms showed another 7 mm AVM fed by the left frontopolar artery. We treated both cerebral AVMs bv gamma knife radiosurgery. Follow-up angiograms performed 2 years after radiosurgery confirmed the disappearance of both AVMs. We then discuss treatment of multiple cerebral AVMs.

[A case of cranial metastasis of hepatocellular carcinoma].

A case of cranial metastasis of hepatocellular carcinoma is reported. A 77-year-old woman with an elastic hard tumor in the right temporal region was referred to our department on April 30, 1992. On admission, the patient had slight weakness of the left upper limb. Plain skull X-ray and computed tomography (CT) showed bone destruction in the right temporal region. Magnetic resonance images (MRI) showed that the tumor was hypo-intense with T1-sequences and hyper-intense with T2-sequences, and included hyper-intense spots on both T1- and T2-images. Right carotid angiography showed that the tumor was fed by the middle meningeal and accessory meningeal arteries. The patient became disoriented, and the left hemiparesis worsened on May 4, 1992. CT scan revealed an irregular high-density area in the tumor because of intratumoral hemorrhage. After embolization of the arteries feeding the tumor, surgery was performed on May 8, 1992, and the tumor was totally removed. Histological examination of the tumor specimen revealed that it was a metastatic hepatocellular carcinoma. The patient died 8 months after initial diagnosis because of hepatocellular carcinoma.

Rapid spontaneous diminution of cisternal blood on computed tomography in patients with subarachnoid hemorrhage.

BACKGROUND: The purpose of this study is to investigate whether rapid spontaneous diminution of cisternal subarachnoid hemorrhage (SAH) alleviates vasospasm in the corresponding arterial territory. METHODS: The subjects were 103 patients in whom initial computed tomography scans were performed within 24 hours after SAH and repeated within 72 hours. We analyzed the effect of diminution of cisternal SAH on vasospasm in 16 sites in each patient. Of the total 1642 cisterns. SAH was found in 1362 (83%), of which 539 (40%) had a decrease in SAH. The highest diminution rate was 64% in quadrigeminal cistern, and the lowest rate was 27% in frontal interhemispheric fissure (IHF). In basal frontal IHF, both the incidence of diminution of SAH and its degree were significantly lower in patients with ruptured anterior cerebral artery aneurysms than in those with other site aneurysms, while in suprasellar cisterns, sylvian stems, and sylvian fissures, diminution of SAH was not affected by the side of ruptured aneurysms. The diminution of SAH in basal frontal IHF and sylvian stems was associated with less vasospasm in adjacent arteries. CONCLUSIONS: We concluded that in patients with SAH, rapid spontaneous diminution of cisternal blood, which is affected by several factors, makes vasospasm in the corresponding arterial territory less likely.