All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution.

Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10(6) all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200,000) can leave the capsid and be replaced by water molecules from the outside in about 25 µs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

Free energy profiles for penetration of methane and water molecules into spherical sodium dodecyl sulfate micelles obtained using the thermodynamic integration method combined with molecular dynamics calculations.

The free energy profiles, ΔG(r), for penetration of methane and water molecules into sodium dodecyl sulfate (SDS) micelles have been calculated as a function of distance r from the SDS micelle to the methane and water molecules, using the thermodynamic integration method combined with molecular dynamics calculations. The calculations showed that methane is about 6-12 kJ mol(-1) more stable in the SDS micelle than in the water phase, and no ΔG(r) barrier is observed in the vicinity of the sulfate ions of the SDS micelle, implying that methane is easily drawn into the SDS micelle. Based on analysis of the contributions from hydrophobic groups, sulfate ions, sodium ions, and solvent water to ΔG(r), it is clear that methane in the SDS micelle is about 25 kJ mol(-1) more stable than it is in the water phase because of the contribution from the solvent water itself. This can be understood by the hydrophobic effect. In contrast, methane is destabilized by 5-15 kJ mol(-1) by the contribution from the hydrophobic groups of the SDS micelle because of the repulsive interactions between the methane and the crowded hydrophobic groups of the SDS. The large stabilizing effect of the solvent water is higher than the repulsion by the hydrophobic groups, driving methane to become solubilized into the SDS micelle. A good correlation was found between the distribution of cavities and the distribution of methane molecules in the micelle. The methane may move about in the SDS micelle by diffusing between cavities. In contrast, with respect to the water, ΔG(r) has a large positive value of 24-35 kJ mol(-1), so water is not stabilized in the micelle. Analysis showed that the contributions change in complex ways as a function of r and cancel each other out. Reference calculations of the mean forces on a penetrating water molecule into a dodecane droplet clearly showed the same free energy behavior. The common feature is that water is less stable in the hydrophobic core than in the water phase because of the energetic disadvantage of breaking hydrogen bonds formed in the water phase. The difference between the behaviors of the SDS micelles and the dodecane droplets is found just at the interface; this is caused by the strong surface dipole moment formed by sulfate ions and sodium ions in the SDS micelles.

Molecular dynamics study of free energy of transfer of alcohol and amine from water phase to the micelle by thermodynamic integration method.

Free energy of transfer of methylamine, octylamine, methanol, and octanol from water phase to sodium dodecyl sulfate (SDS) micelle has been calculated using thermodynamic integration method combined with molecular dynamics calculations. Together with the results for alkanes obtained in our previous study [K. Fujimoto, N. Yoshii, and S. Okazaki, J. Chem. Phys. 133, 074511 (2010)], the effect of polar group on the partition of hydrophilic solutes between water phase and the micelle has been investigated in detail at a molecular level. The calculations showed that the molecules with octyl group are more stable in the SDS micelle than in the water phase due to their hydrophobicity of long alkyl chain. In contrast, methanol and methylamine are stable in the water phase as well as in the micelle because of their high hydrophilicity. The spatial distribution of methylamine, octylamine, methanol, and octanol has also been evaluated as a function of the distance, R, from the center of mass of SDS micelle to the solutes. The distribution shows that the methylamine molecule is adsorbed on the SDS micelle surface, while the methanol molecule is delocalized among the whole system, i.e., in the water phase, on the surface of the micelle, and in the hydrophobic core of the micelle. The octylamine and octanol molecules are solubilized in the SDS micelle with palisade layer structure and are not found in the water phase.

Molecular dynamics study of solubilization of immiscible solutes by a micelle: Free energy of transfer of alkanes from water to the micelle core by thermodynamic integration method.

Free energy of transfer, DeltaG(w-->m), from water phase to a sodium dodecyl sulfate (SDS) micelle core has been calculated for a series of hydrophobic solutes originally immiscible with water by thermodynamic integration method combined with molecular dynamics calculations. The calculated free energy of transfer is in good correspondence to the experiment as well as the theoretical free energy of transfer. The calculated DeltaG(w-->m)'s are all negative, implying that the alkane molecules are more stable in the micelle than in the water phase. It decreases almost linearly as a function of the number of carbon atoms of the alkanes longer than methane with a decrement of 3.3 kJ mol(-1) per one methylene group. The calculated free energy of transfer indicates that, for example, at the micelle concentration of 50 CMC (critical micelle concentration), about only 1 of 6 micelles or 1 of 32 000 micelles does not contain a solute methane or n-octane molecule, respectively.

[Surgical treatment for Pancoast tumors--significance of surgical approach and induction chemoradiotherapy].

We analyzed 46 patients with Pancoast tumor who underwent surgical resection. Anterior approach was employed for 16 patients and hook approach for 30 patients. Twenty-one patients received preoperative treatment; chemotherapy for 1 patient, radiotherapy for 11 patients, and chemoradiotherapy for 9 patients. Complete resection was achieved in 59% (27/46) of patients. The overall 5-year survival rate was 10.9%. Five-year survival was significantly higher in the patients received complete resection than the patients received incomplete resection (18.5 vs 0%, p=0.0016). The complete resection rate has improved in recent cases, and one of the reasons seems to be the adoption of preoperative chemoradiotherapy. But postoperative complications occurred more frequently in patients who received induction therapy than the others. Optimal selection of surgical approach and induction chemoradiotherapy for Pancoast tumors appear to provide improved complete resection rate and long term survival.

Multiple intravascular papillary endothelial hyperplasia affecting skin and bone.

We report a 75-year-old man with multiple recurrent black papules involving his entire body. In the course of 3 years, 20 lesions were resected, which were histologically confirmed as intravascular papillary endothelial hyperplasia (IPEH). A similar vascular lesion was found on his tibia. The occurrence of multiple IPEH affecting skin and bone is extremely rare. The patient's medical history included hepatitis C, hepatoma and associated coagulopathy. We suggest that this patient's multiple lesions were induced by microthrombus formation due to liver dysfunction.

[Evaluation of tracheobronchoplasty for lung cancer].

Tracheobronchoplasty has become one of the standard procedures for lung cancer. In this study, we examined the incidence of complications and survival of tracheobronchoplasty and compared with these of pneumonectomy. In 119 patients underwent tracheobronchoplasty, bronchopleural fistula occurred in 6 (5.0%) and anastomotic stenosis occurred in 5 (4.2%). Five-year survival rate of 119 patients underwent tracheobronchoplasty was 47.3%, and the median survival time was 49.3 months. We compared the sleeve or wedge lobectomy and pneumonectomy, the incidence of complications and 30-days death were similar, but the rate of in-hospital death and the prognosis of the sleeve or wedge lobectomy were better than these of pneumonectomy. So to preserve a respiratory function, we should use a bronchoplastic procedures to avoid pneumonectomy.

Ambiguus motoneurons discharging closely associated with ultrasonic vocalization in rats.

Unitary discharges closely associated with ultrasound were recorded from the nucleus ambiguus (NA) and adjacent medullary regions in rats. Two main types of units were distinguished: one firing in tonic bursts against little or no background activity prior to ultrasound emission, and the other remaining silent during ultrasound. Tonic burst units in NA are considered as motoneurons which are essential for ultrasound vocalization since lesions including NA completely abolished its production.

Identification of ultrasonic vocalization substrates determined by electrical stimulation applied to the medulla oblongata in the rat.

The aim of the present investigation was to identify the neural structures, within the rat medulla, that are responsible for rodent ultrasound production. Sound producing substrates were found to be located in the reticular formation and some cranial nerve nuclei as well as several other nuclei situated in the lateral and dorsomedial portions of the medulla. To estimate the degree of involvement in the generation of ultrasound signals, the sound response latencies were measured for each structure. The lateral reticular nucleus and the facial nucleus showed latencies that were significantly shorter than those for other nuclei, and they were assumed to have a primary part in rodent ultrasound production. Audible sounds of considerably longer latencies were produced exclusively by stimulation of the trigeminal spinal tract nucleus. No ultrasounds could be obtained in this region. These results were discussed in terms of innervations of the facial and laryngeal musculature by the specific neural structures. Present results were also discussed with reference to the roles of the bulbar monoaminergic neurons projecting to the spinal cord and the role of ascending nociceptive pathways.

The midbrain central gray substance as a highly sensitive neural structure for the production of ultrasonic vocalization in the rat.

To test whether there were any functional differences between the central gray substance (PVG) and other neural structures for the production of ultrasonic vocalization in the rat, an electrical stimulation experiment was systematically undertaken in diencephalic and mesencephalic tegmental regions. The sound production sensitivity to electrical stimulation was the highest in PVG. This suggested that the periventricular fiber system of Schütz's bundle might be a possible neural structure underlying sound emission in the rat.

Hypothalamic projection to the pulvinar-LP complex in the cat: a study by the silver impregnation method.

This study was designated to determine the exact terminal portion of the hypothalamo-thalamic projection found in our previous study by the HRP method [7]. Electrolytic lesions were made in the brains of 13 adult cats, and the ensuing degenerating fibers were impregnated with Nauta-Gygax and Fink-Heimer methods. Following the lesions of the hypothalamic small nucleus which had been reported to receive abundant HRP transport from the pulvinar-LP complex, terminal degeneration concentrated in the dorsolateral marginal area of LP, forming a well-defined and dorsomedially stretched slim column along the medial border of the pulvinar. The level of its appearance approximately corresponds with the stereotaxic coronal plane, Fr. 7.0. In the contralateral same thalamic area the degenerating fibers were also traced though they were much fewer.

The discrepancy in hardness between clinical and histopathological findings in localized scleroderma treated with PUVA.

Topical PUVA therapy was applied to a patient with localized scleroderma. Her localized scleroderma responded very well to the topical PUVA therapy, i.e., her sclerotic skin softened to normal skin texture. However, despite this dramatic clinical change the histopathological findings did not change at all and were still "hard".

Mobility of the cervical spine after anterior interbody fusion for spondylotic myelopathy-a radiographic study.

To study the influence of anterior body fusion on the adjacent vertebral discs, the radiographs of 101 patients with cervical spondylotic myelopathy (CSM) were analysed, and cervical mobility and intersegmental mobility were determined. Single level fusions were carried out in 29 patients, double level fusions in 45 patients and triple level fusions in 27 patients. Cervical mobility after surgery was inversely proportional to the number of fused discs. Angles were reduced by fusion in proportion to the number of fused discs. The compensatory increase in motion at the disc adjacent to the fusion was slight, and the number of fused discs had little influence on the compensatory increase in motion. Regarding cervical motion, extension and flexion were limited to the same extent in single level fusions, flexion was more limited in double level fusions and limitation of extension was much larger in triple level fusions. Seven patients underwent a second operation after a double level fusion, and one patient underwent a second operation after a single level fusion. In all five patients whose radiographs before the second operation were available, flexion was adequately limited, but extension was not limited at all. These results suggest that the failure to limit extension is responsible for the recurrence of CSM.

Demonstration of focal brain ischemia induced by hyperventilation using Tc-99m HMPAO SPECT.

A case with vasospasm of the right anterior cerebral artery induced by hyperventilation is presented. Consecutive Tc-99m HMPAO brain SPECT studies at rest and during hyperventilation greatly contributed to the quantitative evaluation of focal perfusion decrease in conjunction with contrast angiography. This technique seems to be useful for the detection of alterations in regional brain perfusion during short duration intervention.

[Studies on recurrence of cerebral aneurysm after operation].

It seems to be well established that the direct surgical treatment of intracranial aneurysm such as clipping, trapping and wrapping the aneurysm. These operations have brought about excellent results but are not perfect because recurrent aneurysm and rebleeding of aneurysm have been reported shortly after the operation. However, it is very rare that subarachnoid hemorrhage arising from recurrent aneurysm long time after the operation, authors have experienced 3 cases of recurrent aneurysm in the same region long after the surgery. Two cases were readmitted to our hospital following repeat episode of subarachnoid hemorrhage. Carotid angiogram showed a new small aneurysm locating about the same place where previously operated aneurysm was situated. One of them showed development of new aneurysm at the anterior communicating after 4 years artery the neck clipping, the other one was recurrent aneurysm 9 years after the neck clipping of aneurysm at the anterior communicating artery. Two cases were treated by reclipping and got well. It has been reported in the articles that 20 cases of recurrent aneurysm were located about the same place where previously clipping aneurysm was performed. Causes of such recurrence of already clipped aneurysm could be divided into two groups. First group was considered that the treatment was unsatisfactory, because the clip had been improperly placed. The other group was considered as mechanical failure of aneurysmal clip that resulted in "slipped out," or "broken clip", and local fragility of the arterial wall adjacent to clip edge. Last case had a giant pseudoaneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)