Polarizable Molecular Block Model: Toward the Development of an Induced Dipole Force Field for DNA.

For flexible and highly ionized macromolecules such as DNA, it is important to correctly evaluate the intramolecular polarization in an induced dipole force field. In a proposed polarizable molecular block (PMB) model, a large molecule is divided into several molecular blocks. The atomic charges of the blocks are optimized by using the respective electrostatic potentials (ESPs) on the molecular surface. By using the capped hydrogen removal operation, the total charge of the blocks is controlled exactly to have an integer charge. The atomic polarizabilities of the blocks are optimized by using the respective polarized one-electron potentials that are the differences between ESPs with and without an external test charge. Induced dipole-charge interactions between the blocks are all included, but those interactions within the blocks are strictly excluded. All dipole-dipole interactions are included, but the damping functions are applied to the close dipole-dipole pairs. Several types of damping (simple scaling, exponential, linear, and Gaussian) are evaluated. The validity of the PMB model was verified by using trinucleotide duplexes which have A-, B-, and Z-DNA forms. The reference energies of trinucleotide duplexes including counterions (GGT3Na-ACC3Na, GAC3Na-GTC3Na, and GCG3Na-CGC3Na) are calculated using ωB97XD/aug-cc-pVDZ. All damping types reproduced well the reference interaction energies, dipole moments, and ESPs. Among them, the simple scaling with strong attenuation to 1-2 atomic pairs showed the highest stability against the polarization catastrophe. This study shows that it is possible to develop a high-quality polarizable force field by treating the intramolecular polarization on a block-by-block basis.

New aneurysm formation and regrowth associated with rebleeding of residual pediatric ruptured arteriovenous malformation: patient series.

BACKGROUND: If complete obliteration of ruptured pediatric arteriovenous malformation (AVM) cannot be achieved, the appropriate follow-up duration and predictors of rebleeding remain unknown. OBSERVATIONS: Pediatric patients with ruptured AVMs admitted to the authors' hospital within the past 30 years were evaluated. Rebleeding was confirmed in two patients. The first patient was a 5-year-old boy who experienced right thalamic hemorrhage. AVM was found in the bilateral thalamus and treated with stereotactic radiosurgery (SRS). New aneurysm formation and residual AVM regrowth were confirmed 21 years after the SRS. Eight months later, rebleeding occurred. The second patient was a 5-year-old boy who underwent removal of a left cerebellar hemorrhage and AVM. The residual AVM was treated with SRS. Residual AVM regrowth was detected at 6 years 7 months after SRS. Five months later, new aneurysm formation was confirmed. Two additional days later, rebleeding occurred. LESSONS: New aneurysm formation and residual AVM regrowth may predict rebleeding and can occur >20 years after the initial rupture and treatment. If AVM obliteration is not achieved, long-term follow-up is needed, even in adulthood, with attention to new aneurysm formation and residual AVM regrowth. Further treatment is recommended if these findings are confirmed.

Gliosarcoma with unusual glial components: Two case reports.

Gliosarcoma is characterized by the presence of alternating lesions of glial and mesenchymal components. Although many mesenchymal components have been reported, there are few reports on glial components. We here report two cases of gliosarcoma. Case 1 was a 42-year-old woman with right hemiparesis and motor aphasia. Magnetic resonance imaging (MRI) identified a tumor in the left frontal lobe. Pathological analysis of the tumor removal specimen revealed gliosarcoma, with a glial component resembling pleomorphic xanthoastrocytoma. Postoperatively, radiotherapy and chemotherapy were conducted, and the patient was symptom-free over 12 months after surgery. Case 2 was a 67-year-old woman with a consciousness disorder and left hemiparesis. MRI revealed a tumor in the right frontal lobe. Pathological analysis of the first tumor removal specimen identified gliosarcoma, with a glial component characterized by large tumor cells. Additionally, the Ki-67 labeling index of the glial component was greater than that of the mesenchymal component, and molecular genetic analysis disclosed a mutation in the telomerase reverse transcriptase (TERT) gene (TERT). Chemotherapy and radiotherapy were performed. Four months later, MRI revealed recurrence, and the second surgery was performed. Pathological analysis revealed giant cell glioblastoma without TERT mutation. The patient died due to tumor progression 12 months after the first surgery. It is essential to continue histopathological evaluation of glial components, and further genetic evaluation on gliosarcoma is required.

The Shunt Point of the Sacral Dural Arteriovenous Fistula: A Case Report and Literature Review.

BACKGROUND: The occurrence of sacral dural arteriovenous fistula (dAVF) is rare. The detailed vascular architecture of sacral dAVF, including 3-dimensional (3D) angiographic images with operative findings, has not been evaluated compared with that of the thoracic and lumbar levels. We report a case of sacral dAVF with 3D angiographic examination and operative findings, with a literature review. CASE DESCRIPTION: A 60-year-old man presented with progressive urinary incontinence and gait disturbance. A sacral dAVF was detected at the S1-2 level. The shunt point was at the medial side of the line between the intermediate sacral crest and the most medial point of the L5 pedicle circle at the anterior posterior view of the angiography; we defined this type as the medial type. After embolization, latent inflow arteries were visualized ipsilaterally and contralaterally. During surgery, because of dAVF recurrence, a vascular tangle was found on the dura. The surgical interruption of the draining vein improved the patient's symptoms. From the literature review, 92% of cases had medial-type shunt point. It is possible for sacral dAVF to have multiple inflow arteries originating ipsilaterally or bilaterally, and a venous pouch. CONCLUSIONS: The shunt point of sacral dAVF tended to be located medially, not in the sacral foramen. Sacral dAVF has unique angioarchitecture. The differentiation of dAVF from epidural arteriovenous fistula may not be easy in some cases of sacral lesions. Therefore, further studies with a larger number of patients focused on the detailed vascular architecture are needed.

Evaluation of the Partial Re-Sheathing Technique with the Solitaire Stent Retrieval System In Vitro Model and a Representative Case.

Objective: Vascular injuries are severe complications associated with endovascular thrombectomy. In the present study, we evaluated the re-sheathing technique with the Solitaire stent retrieval system to overcome these complications. Methods: We examined the diameter and resistance to retrieval of the Solitaire FR device (6 × 20 mm) during full and partial deployment in vitro model. We also examined a representative case in which the re-sheathing technique was used. Results: We found that the Solitaire device spread elliptically during partial deployment. As the length of the partially deployed device decreased, the maximum diameter also decreased. The distal half of the stent retained 80% of the maximum diameter of the partially deployed Solitaire. The resistance to retrieval was significantly higher during full deployment (mean ± standard deviation; 0.32 ± 0.04 kg) than during half deployment (0.22 ± 0.04 kg) (Mann-Whitney U test; p = 0.006). The re-sheathing technique was used in the representative case due to the high resistance to retrieval, which enabled recanalization without extravasation. Conclusion: In cases of high resistance to retrieval, minimal re-sheathing may be useful for capturing the thrombus without increasing the risk of vascular injury.

Usefulness of Stent-Assisted Coil Embolization of Direct Traumatic Carotid-Cavernous Fistulas: Report of Three Patients and Review of Other Treatment Methods.

Objective: Direct traumatic carotid-cavernous fisulas (dtCCFs) exhibit a high blood flow velocity and are often difficult to be treated. We report three dtCCF cases in which disappearance of the dtCCF and preservation of the internal carotid artery (ICA) were achieved by stent-assisted coil embolization of the fistula. We report these cases and compare them with those previously reported using other treatments. Case Presentations: In the first case, we performed coil embolization without stenting for the initial treatment. The cerebral venous reflux disappeared and the patient's symptoms were temporarily ameliorated. However, 5 months after treatment, an aneurysm-like finding around the fistula was noted on MRA. Additional coils and insertion of a neck-bridging stent were required to obliterate the dtCCF and the symptoms disappeared. In the second and third cases, we intended to use stents initially to achieve tight embolization of the fistulas, and obliteration was achieved. Conclusion: Use of neck-bridging stenting for dtCCFs may be a reliable method to preserve the parent artery while achieving tight packing around the fistula.

Dual Photochemical Reaction Pathway in Flavin-Based Photoreceptor LOV Domain: A Combined Quantum-Mechanics/Molecular-Mechanics Investigation.

The primary photochemical reaction of the light, oxygen, and voltage (LOV) domain of the blue-light photosensor YtvA of Bacillus subtilis were investigated using high-level QM(DFT/MRCI)/MM methods. After blue-light excitation, the Sγ atom of the reactive cysteine forms a covalent bond with the C4a of the flavin mononucleotide (FMN) ring. Two conformations for the side chain of reactive cysteine with occupancies of 70% (conf A) and 30% (conf B) are observed in the X-ray crystallographic structures of the YtvA-LOV ( Möglich , A. ; Moffat , K. J. Mol. Biol. 2007 , 373 , 112 - 126 ). In conf A, the thiol group is directed toward the dimethylbenzene moiety of the FMN ring whereas it is placed directly above the N5 atom of the FMN ring in conf B. Starting from both conformations, the singlet and triplet excited pathways were evaluated. The singlet states excited from conf A decay nonradiatively to the triplet states by intersystem crossing (ISC). After the formation of a neutral biradical, the triplet states cross over to the electronic ground state by a second ISC and the adducts are efficiently formed. The singlet states excited from conf B are located near the S1/S0 conical intersection (CIn). A major fraction returns to the initial states through the CIn. The rest may directly reach the adduct state. Thus, the photoexcitation has a dual reaction pathway. In YtvA-LOV, it is inferred that the efficient triplet excitation from conf A was chosen by bypassing the less efficient singlet excitation from conf B.

Gliosarcomas arising from the pineal gland region: uncommon localization and rare tumors.

Gliosarcomas are a variant of glioblastomas and present a biphasic pattern, with coexisting glial and mesenchymal components. In this study, two unusual cases are presented. Case 1 is a 52-year-old woman with a headache and memory disturbance for a month. Case 2 is an 18-year-old man with a headache lasting two weeks. In both cases, an MRI revealed enhancing T1-low to iso, T2-iso to high intensity lesions in the pineal gland region. Histologically, in case 1, the tumor showed spindle cell proliferation with disorganized fascicles and cellular pleomorphism. Tumor cells variously exhibited oncocytic transformation. Immunohistochemically, most of the spindle tumor cells were positive for myoglobin and desmin. Some of the tumor cells were positive for GFAP and S-100 protein. On the other hand, all tumor cells were positive for CD133, Musashi1, and SOX-2 which are the markers of neural stem cells. In case 2, the tumor showed monotonous proliferation of short spindle cells with disorganized fascicles and cellular atypism. The morphological distinction between glial and mesenchymal components was not apparent. Immunohistochemically, most of the spindle tumor cells were positive for desmin. Glial tumor cells that were dispersed within the sarcoma as single cells were positive for GFAP. In addition, all tumor cells were positive for CD133, Musashi1 and SOX-2. Based on these microscopic appearances, and immunohistochemical findings, these cases were diagnosed as gliosarcomas arising from the pineal gland region. These results also indicated that pluripotential cancer stem cells differentiated into glial and muscle cell lines at the time of tumor growth. In a survey of previous publications on gliosarcoma arising from the pineal gland, these cases are the second and third reports found in English scientific writings.

Photophysics of flavin derivatives absorbing in the blue-green region: thioflavins as potential cofactors of photoswitches.

The purpose of this study was to find flavin derivatives with absorption maxima in the blue-green region of the visible spectrum that might be used as alternative cofactors in blue-light photoreceptors. To this end, the vertical absorption spectra of eight lumiflavin-related compounds were calculated by means of quantum chemical methods. The compounds differ from lumiflavin by the subsitution of an S atom for an O atom at the 2- and/or 4-positions of the isoalloxazine core, the substitution of an N atom for a CH group in the 6- and/or 9-positions, or an extension of the π system at the 7- and 8-positions. For the three most promising compounds, 2-thio-lumiflavin, 4-thio-lumiflavin, and 2,4-dithio-lumiflavin, the quantum chemical investigations were extended to include geometry relaxations in the excited states, rates for spin-forbidden transitions and an estimate of spectral shifts brought about by polar protic environments. We find these thiocarbonyl compounds to have very promising excited-state properties. They absorb in the blue-green wavelength regime around 500 nm, i.e., substantially red-shifted with respect to lumiflavin that is the cofactor of natural blue-light photoreceptors. Their triplet quantum yields are predicted to be close to unity while their triplet lifetimes are long enough to enable bimolecular photochemical reactions. The combination of these properties makes the thioflavins potentially suitable candidates as cofactors in biomimetic photoswitches.

Polarizable model potential function for nucleic acid bases.

A polarizable model potential (PMP) function for adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) is developed on the basis of ab initio molecular orbital calculations at the MP2/6-31+G* level. The PMP function consists of Coulomb, van der Waals, and polarization terms. The permanent atomic charges of the Coulomb term are determined by using electrostatic potential (ESP) optimization. The multicenter polarizabilities of the polarization term are determined by using polarized one-electron potential (POP) optimization in which the electron density changes induced by a test charge are target. Isotropic and anisotropic polarizabilities are adopted as the multicenter polarizabilities. In the PMP calculations using the optimized parameters, the interaction energies of Watson-Crick type A-T and C-G base pairs were -15.6 and -29.4 kcal/mol, respectively. The interaction energy of Hoogsteen type A-T base pair was -17.8 kcal/mol. These results reproduce well the quantum chemistry calculations at the MP2/6-311++G(3df,2pd) level within the differences of 0.6 kcal/mol. The stacking energies of A-T and C-G were -9.7 and -10.9 kcal/mol. These reproduce well the calculation results at the MP2/6-311++G (2d,2p) level within the differences of 1.3 kcal/mol. The potential energy surfaces of the system in which a sodium ion or a chloride ion is adjacent to the nucleic acid base are calculated. The interaction energies of the PMP function reproduced well the calculation results at the MP2/6-31+G* or MP2/6-311++G(2d,2p) level. The reason why the PMP function reproduces well the high-level quantum mechanical interaction energies is addressed from the viewpoint of each energy terms.

Recipe of Polarized One-Electron Potential Optimization for Development of Polarizable Force Fields.

Polarized one-electron potential (POP) optimization is a powerful and practical method to determine multicenter dipole polarizabilities that can be used for constructing polarizable force fields. The POP optimization is similar to the widely used electrostatic potential (ESP) optimization to determine the partial charges of molecules. However, while the ESP optimization targets the electrostatic potentials on a molecular surface, the POP optimization targets the change of electrostatic potentials on molecular surfaces which are induced by the field of a test charge on the molecular surface. Since only additional one-electron integrals for the test charge are required for the estimation of the surface potentials, the change of electrostatic potentials has been named "polarized one-electron potentials". We show that in the POP optimization, both an explicitly interacting polarizability model and an implicitly interacting polarizability model can be used for the determination of the multicenter polarizabilities. In the explicitly interacting model, intramolecular induced dipole-induced dipole interaction is mutually included in the process of the POP optimization, but the interaction is not included in the implicitly interacting model. In the implicitly interacting polarizability model, a combined model of isotropic atom polarization and anisotropic bond polarization is shown to provide the best fitting results for nucleic acid bases which show large polarization anisotropy. A simple scaling model to the chemical bond has been newly proposed for the explicitly interacting polarizability model. We show that the simple model can be applied to molecular simulations without any damping of exponential type in the intramolecular induced dipole interaction. A detailed procedure for determination of the multicenter dipole polarizability by the POP optimization is also presented.

Postoperative infection after duraplasty with expanded polytetrafluoroethylene sheet.

Dural reconstruction is a significant problem in many cases of decompressive craniotomy and dural defect. Expanded polytetrafluoroethylene (ePTFE) sheet have been used as a dura mater substitute for duraplasty. The outcomes of 83 consecutive patients at our institution were reviewed who underwent external decompression and closure with the ePTFE sheet between August 1995 and December 2000. Eight cases of infection occurred. Seven patients had infection with subdural empyema after cranioplasty with autologous bone. Three patients improved after removal of only the infected bone. One patient improved after removal of the infected bone and ePTFE sheet. One patient experienced wound infection after the original operation. Four patients subsequently developed local and severe inflammation with skin erythema until the ePTFE sheet was removed. Four patients had severe recurrent infections which required subsequent therapy such as vascularized free rectus abdominis muscle flap transfer. Duraplasty with ePTFE sheet might promote infection and poor circulation in the skin flap. The ePTFE sheet should be removed at an early stage in a patient with infection.

[Spontaneous epidural hematoma in a patient undergoing hemodialysis: a case report].

A 54-year-old male with chronic renal failure due to diabetic nephropathy suffered dysphagia and left facial spasm without head trauma during a hemodialysis session. CT scan revealed a right acute epidural hematoma. MRI and cerebral angiography did not reveal any abnormalities in the intracranial vasculature. The occurrence of intracranial spontaneous epidural hematoma in a haemodialysis patient has not been reported. During hemodialysis, the intracranial pressure transiently increases and rapidly recovers. It is assumed that the decreasing intracranial pressure caused epidural hematoma.

Subarachnoid hemorrhage caused by dural arteriovenous fistula of the sphenobasal sinus--case report.

A 59-year-old woman presented with a rare middle fossa dural arteriovenous fistula (AVF) unrelated to the cavernous sinus manifesting only as subarachnoid hemorrhage. Angiography revealed shunts between the meningeal branches of both the internal and external carotid arteries and the sphenobasal sinus. The AVF drained into the superficial middle cerebral vein (SMCV) which had a varix and an anastomosis to a superior cerebral vein. The arterial supply vessels were eliminated surgically and the sinus was excised. Bleeding did not recur and there was no venous infarction. Dural AVF of the sphenoparietal sinus is associated with pulsatile exophthalmos and dural AVF of the sphenopetrosal sinus with tinnitus, but dural AVF of the sphenobasal sinus has no obvious symptom. Simple interruption of the SMCV at the penetration of the arachnoid membrane was possible because of the absence of a draining vessel to preserve AVF patency, but the arteries were eliminated in this patient to prevent formation of another AVF.

[Dissecting aneurysm of the middle cerebral artery with subarachnoid hemorrhage showing complete occlusion at the M2 portion of the middle cerebral artery on preoperative angiograms: case report].

We present a surgical case of a dissecting aneurysm of the middle cerebral artery associated with subarachnoid hemorrhage and intracranial hemorrhage. A 29-year-old man suddenly fell into a comatose state, and was referred to our hospital. CT scan showed diffuse subarachnoid hemorrhage and an intracerebral hematoma with marked midline shift located in the right frontal lobe. The right carotid angiogram revealed complete occlusion at the M2 portion of the middle cerebral artery, but failed to reveal any aneurysms in the rest of the intracranial circulation. We undertook emergent surgery to evacuate the hematoma and to confirm whether it was a dissecting aneurysm or not. After evacuation of the hematoma of the right frontal lobe, the Sylvian fissure was noticed to be widely opened. We detected a large dissecting aneurysm with a dark-purplish wall arising from the right M2 trunk, and we trapped the aneurysm. The postoperative course was uneventful and the patient gradually improved and was discharged without neurological deficits. We presented this case with a review of the literature.

[A case of cervical pyogenic spondylitis difficult to differentiate from metastatic spinal tumor].

A 52-year-old man with medical complications of diabetic mellitus and alcoholic liver dysfunction, presented with weakness in the bilateral lower extremities. Cervical magnetic resonance images disclosed the lesion extended from retropharyngeal space and multiple vertebral bodies to epidural space of the spinal canal, which was enhanced by gadolinium. Not only fever elevation during clinical course but also inflammatory reaction on selologic examination were not identified, so we initially thought the lesion metastatic spinal tumor. In researching original foci, his clinical condition worsened with gate disturbance and urinary incontinence. Eleven days later after admission, laminectomy from C-5 to Th-1 and open biopsy of the lesion was performed. The vertebral bodies exposed via the right frontal approach were covered by thick whitish membrane. Small mount of pus emerged after incision of the membrane, so we diagnosed the lesion pyogenic spondylitis. After the operation, high dose antibiotic therapy for 6 weeks was performed. Follow-up cervical MR imaging 4 months after the operation found that the volume of the lesion and compression of the spinal cord were reduced. The gate disturbance and urinary incontinence gradually improved, he was able to walk with a cane 6 months later.