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Recent advances have fundamentally changed the ways in which synthetic amino acids are incorporated into proteins, enabling their efficient and multiple-site incorporation, in addition to the 20 canonical amino acids. This development provides opportunities for fresh approaches toward addressing fundamental problems in bioengineering. In the present study, we showed that the structural stability of proteins can be enhanced by integrating bulky halogenated amino acids at multiple selected sites. Glutathione S-transferase was thus stabilized significantly (by 5.2 and 5.6 kcal/mol) with 3-chloro- and 3-bromo-l-tyrosines, respectively, incorporated at seven selected sites. X-ray crystallographic analyses revealed that the bulky halogen moieties filled internal spaces within the molecules, and formed non-canonical stabilizing interactions with the neighboring residues. This new mechanism for protein stabilization is quite simple and applicable to a wide range of proteins, as demonstrated by the rapid stabilization of the industrially relevant azoreductase.

Posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid haemorrhage (SAH). We present a case involving a patient who developed PRES, prior to induction of hypertensive therapy, 2 days after the onset of a SAH due to a ruptured intracranial aneurysm.

Object: The prevalence of patients with asymptomatic unruptured intracranial aneurysms (UIAs) increases with the advancing age of the general population. The goal of the present study was to identify risk factors for the growth of UIAs detected with serial MR angiography (MRA) in patients 70 years of age or older., Methods: This prospective study enrolled 79 patients (age range 70-84 years) with 98 UIAs. Patients were followed up every 4 months, including an assessment of the aneurysm diameter and morphological changes on MRA, neurological status, and other medical conditions. Aneurysm growth was categorized into two different patterns on the basis of the MRA findings: 1) maximum increase in aneurysm diameter of 2 mm or more; and 2) obvious morphological change, such as the appearance of a bleb., Results: The mean duration of follow-up was 38.5 months (250.2 patient-years). Aneurysm rupture did not occur, but aneurysm growth was observed in 8 aneurysms (8 patients) during the study period. Univariate analysis showed that female sex, patient age ≥ 75 years, and an aneurysm location in the internal carotid artery (ICA) or middle cerebral artery (MCA) were associated with aneurysm growth (p = 0.04, p = 0.04, and p < 0.001, respectively). Multivariate analysis demonstrated that female sex was the only independent predictor of aneurysm growth (p = 0.0313, OR 2.3, 95% CI 1.3-30.2)., Conclusions: Female sex is an independent risk factor for the growth of UIAs in elderly patients. In addition, an age ≥ 75 years and aneurysm location in the ICA or MCA are characteristics that may warrant additional attention during follow-up imaging.

Background: Patients with aneurysmal subarachnoid hemorrhage (SAH) typically develop appetite loss. However, the mechanisms regulating appetite are not understood. Ghrelin and leptin, both of which signal nutritional status and energy storage levels to the hypothalamus, are essential elements of the appetite system. Thus, the goal of this study was to investigate the relationship between appetite and ghrelin and leptin concentrations in patients with SAH., Methods: Blood plasma or serum profiles and appetite status were measured in 19 patients with SAH who underwent aneurysmal clipping within 48 hours of SAH onset. Appetite status was measured using dietary oral calorie intake. All outcome variables were measured at an early (day 3) and late (day 8) time point after SAH onset (day 0)., Results: Of the 19 patients studied, 6 (31.6%) showed lower dietary oral calorie intake at the late time point than at the early time point. In these patients with appetite loss, plasma hemoglobin (P < 0.02), albumin (P < 0.01), glucose (P < 0.01), plasma insulin (P < 0.04), and serum ghrelin (P < 0.03) concentrations were lower at the late time point than at the early time point. Serum leptin was higher at the late time point than at the early time point (P < 0.02)., Conclusion: In SAH patients, appetite loss may be induced by lower serum ghrelin and higher serum leptin concentrations resulting from high plasma glucose and insulin levels due to a catecholamine surge following SAH.

Objective: Adrenomedullin (AM) is secreted into the cerebrospinal fluid (CSF) from the choroid plexus and regulates appetite. Adrenomedullin concentration in the CSF is elevated 7-10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentration is related to appetite and delayed ischemic neurological deficits (DIND) after SAH., Methods: Adrenomedullin concentration in the CSF, blood plasma profile, and appetite status were measured in 22 patients with SAH who underwent aneurysmal clipping within 48 hours of SAH onset. Appetite status was measured using dietary oral calorie intake and self-reported appetite level. All outcome variables were measured at an early (Day 3) and late (Day 8) time point after SAH onset (Day 0)., Results: Dietary oral calorie intake (P = 0·02), self-reported appetite level (P = 0·03), hemoglobin (P = 0·01), albumin (P = 0·03), glucose (P = 0·01), and insulin (P = 0·03) levels were lower at the late time point than at the early time point. Cerebrospinal fluid adrenomedullin concentration was higher at the late time point than at the early time point (P = 0·0007). There was a significant negative correlation between AM concentration and dietary oral calorie intake (r = -0·478, P = 0·024) and self-reported appetite level (r = -0·454, P = 0·033) at the late time point. Six patients (27%) developed DIND. Adrenomedullin concentration at the late time point was significantly higher in patients who developed DIND than in patients who did not (P = 0·02)., Conclusions: Cerebrospinal fluid adrenomedullin concentration 8 days after SAH onset is related to appetite loss and DIND.

Background/aims: Although proximal gastrectomy has become a procedure of choice for patients' early cancer in the upper third of stomach, no clinical guide for optimal gastric resection in order to avoid postoperative jejunal ulcer is available. The aim of this study was to investigate whether determining the distribution of parietal and chief cells of the stomach using Congo red test is clinically relevant., Methodology: The F-line was defined as a boundary line between fundic and intermediate area of the stomach according to the pathological findings in 29 patients who underwent total gastrectomy for early gastric cancer, whereas the f-line was regarded as a boundary line between intermediate and pyloric area. In the additional 6 patients undergoing vagus-preserving proximal gastrectomy with jejunal pouch interposition, endoscopic Congo red test was preoperatively performed to determine the F-f-line., Results: The distances from the pyloric ring to f-line on the lesser and greater curvatures were variable. Long-term outcomes of proximal gastrectomy guided by preoperative endoscopic Congo red test were favorable., Conclusions: It is suggested that preoperative endoscopic Congo red test is useful to determine the appropriate cutting line in order to avoid postoperative jejunal ulcer after proximal gastrectomy.

Tumor grade differentiation is often difficult using routine neuroimaging alone. Computed tomography perfusion imaging (CTP) provides quantitative information on tumor vasculature that closely parallels the degree of tumor malignancy. This study examined whether CTP is useful for preoperatively predicting the grade of malignancy in glioma showing no enhancement on contrast-enhanced magnetic resonance imaging (MRI). Subjects comprised 17 patients with supratentorial glioma without enhancement on MRI. CTP was performed preoperatively, and absolute values and normalized ratios of parameters were calculated. Postoperatively, subjects were classified into two groups according to histological diagnosis of grade 3 (G3) glioma or grade 2 (G2) glioma. Absolute values and normalized ratios for each parameter were compared between G3 and G2. Accuracies of normalized ratios for cerebral blood flow (nCBF) and cerebral blood volume (nCBV) in predicting a diagnosis of G3 were assessed. In addition, nCBV was compared between diffuse astrocytoma, G2 oligodendroglial tumor (OT), and G3 OT. Values for nCBF and nCBV differed significantly between G3 and G2. Using nCBV of 1.6 as a cutoff, specificity and sensitivity for distinguishing G3 were 83.3% and 90.9%, respectively. No significant difference in nCBV was seen between diffuse astrocytoma and G2 OT, whereas differences were noted between G2 and G3 OTs, and between diffuse astrocytoma and G3 OT. CTP offers a useful method for differentiating between G3 and G2 in nonenhancing gliomas.

Nonalcoholic steatohepatitis (NASH) is one of the most frequent causes of abnormal liver dysfunction associated with synthesis and oxidation of fatty acids. Adiponectin receptors (AdipoR1/R2) and insulin receptor substrates (IRS-1/-2) are known as modulators of these fatty acid metabolisms in the liver; however, the regulatory roles of these receptors in the synthesis and oxidation of fatty acids are unclear in the liver of NASH. In this study, we examined the roles of hepatic AdipoR1/R2 and IRS-1/-2 in NASH using an animal model. After feeding a high-fat and high-cholesterol diet to obese fa/fa Zucker rats for 8 weeks, rats showed fatty liver spontaneously with inflammation and fibrosis that are characteristic of NASH. The expression levels of AdipoR1/R2 and IRS-2 were significantly decreased, whereas IRS-1 was significantly increased, in NASH. As a result of the decrease of AdipoR1/R2 expression, the messenger RNA expression levels of genes located downstream of AdipoR1/R2, adenosine monophosphate-activated protein kinase α1/α2, which inhibits fatty acid synthesis, and peroxisome proliferator-activated receptor α, which activates fatty acid oxidation, also decreased. Expression level of sterol regulatory element binding protein-1c was found to be elevated, suggesting the up-regulation of IRS-1, and resulted in increased fatty acid synthesis. Furthermore, increase of forkhead box protein A2 expression was observed, which might be associated with the down-regulation of IRS-2, facilitating fatty acid oxidation. Taken together, increased synthesis and oxidation of fatty acids by up- or down-regulation of AdipoR or IRS may contribute to the progression of NASH. Thus, AdipoR and IRS might be crucially important regulators for the synthesis and oxidation of fatty acids in the liver of NASH., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An important source of reactive oxygen species (ROS) production is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which on activation induces superoxide production via oxidation in the mitochondria, inflammation and stress; such ROS are implicated in the pathogenesis of diabetic complications, including neuropathy. Hyperbaric oxygen (HBO) treatments are applied various diseases including diabetic patients with unhealing foot ulcers, however, and also increases the formation of ROS. In a previous study, we showed that a clinically recommended HBO treatment significantly enhanced oxidative stress of pancreatic tissue in the diabetic rats. However, no study has been undertaken with regard to the effects of HBO on the activity and gene expression of the NADPH oxidase complex and on apoptosis in the pancreas of diabetic animals. The purpose of this study was to investigate the effect of HBO exposure on gene expression of the NADPH complex, and pancreatic expression of genes related to apoptosis via the mitochondria, using the NADPH oxidase inhibitor apocynin. The mRNA expression of genes related to NADPH oxidase complex and apoptosis increased significantly (P < 0.05) in the pancreas of diabetic rats under HBO exposure. Similarly, activities of NADPH oxidase and caspase-3 changed in parallel with mRNA levels. These results suggest that oxidative stress caused by HBO exposure in diabetic animals induces further ROS production and apoptosis, potentially through the up-regulation of NADPH oxidase complex. Thus, this study can contribute to development of a better understanding of the molecular mechanisms of apoptosis via the mitochondria in diabetes, under HBO exposure.

We describe a 66-year-old woman with Epstein-Barr virus-associated lymphoproliferative disorder with lung and gastric tumors. We identified two lung tumors measuring 13 and 20 mm in diameter that consisted of CD30-, CD15-, and CD20-positive Hodgkin- and Reed-Sternberg-like cells and heterogeneous cellular infiltrates in a pronounced nodular pattern, with necrosis and vasculitis, diagnosed as nodular sclerosis classical Hodgkin lymphoma. A gastric tumor showed low-grade extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Neoplastic cells in all tumors expressed Epstein-Barr virus-encoded RNA based on in situ hybridization. The present case is a rare composite lymphoma arising from different extranodal organs, associated with EBV infection. Her medical history included gamma-knife therapy for clinical diagnosis with a suspicion of cerebral lymphoma.

Background: When the fundus of an aneurysm is superiorly or posteriorly directed or the anterior communicating artery (ACoA) is located far from the sphenoidal plane, wide dissection of the interhemispheric fissure is needed to expose the ACoA aneurysm., Methods: When the thickened arachnoid membrane covering the dorsal surface of the ipsilateral optic nerves is dissected through the pterional approach, the dissection must not be performed beyond the midline of the optic chiasm. As a result, the undissected arachnoid membrane becomes tense and is easily cut down toward the interhemispheric fissure. We have used this technique in 24 patients in whom the ACoA aneurysm projected superiorly or posteriorly., Results: The gyrus rectus was resected in four patients with ruptured aneurysm because the aneurysmal domes were partially buried in the ipsilateral gyri recti. In the remaining patients, the aneurysmal dome was fully exposed without gyrus rectus resection., Conclusions: The present technique is helpful to dissect the interhemispheric fissure easily and widely by the pterional approach and to expose the ACoA aneurysm adequately., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The mechanical properties of titanium-alloy aneurysm clips after long-term implantation in the human cranium are unclear. The characteristics of a Yasargil titanium aneurysm clip were evaluated after long-term implantation for 12 years in a patient with a cerebral aneurysm. The closing forces of the retrieved clip before and after implantation were approximately equal. The bending test showed no differences between the retrieved and control clips. Titanium oxide and calcium were identified on the surface of the retrieved clip, which indicated the formation of corrosion-resistant layers. Titanium-alloy clips retain their mechanical properties in the human cranium for a long time.

The pathogenesis of nonalcoholic steatohepatitis (NASH) is not well understood; however, the progression of fatty liver to NASH has been linked to oxidative stress and lipid peroxidation in the liver, leading to inflammation. Although the adiponectin receptor 2 (AdipoR2) has been identified as a modulator of oxidative stress and inflammation in the liver, it remains unclear whether the receptor has hepatic antioxidant and anti-inflammatory effects in NASH. In this study, we used an animal model of NASH to examine hepatic AdipoR2. Obese fa/fa Zucker rats fed a high-fat and high-cholesterol (HFC) diet spontaneously developed fatty liver with inflammation and fibrosis, characteristic of NASH, after 4, 8, or 12 weeks of HFC diet consumption. AdipoR2 expression was significantly decreased, whereas the expression of genes related to NADPH oxidase complex were increased. As a result of the decrease in AdipoR2 expression, the mRNA expression of genes located downstream of AdipoR2, i.e., Cu-Zn superoxide dismutase (Cu-Zn SOD) and Mn-SOD, also decreased. Furthermore, the expression of genes related to inflammation was increased. Increased oxidative stress and inflammation by down-regulation of AdipoR2 may contribute to the progression of NASH. Thus, the AdipoR2 might be a crucially important regulator of hepatic oxidative stress and inflammation in NASH.

Background: The prevalence of patients with asymptomatic unruptured intracranial aneurysms (UIAs) will likely increase as the general population ages. The goal of the present study was to prospectively assess cognitive function and anxiety before and after surgical repair of asymptomatic UIAs in patients ≥ 70 years., Methods: A total of 28 patients ≥ 70 years with UIAs underwent cognitive testing using the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale (WMS), and the Rey-Osterrieth Complex Figure test (ROCF) 1 month before and 1 month after surgery. All patients also underwent anxiety testing at these time points using the State-Trait Anxiety Inventory., Results: Group-rate analysis demonstrated that the performance intelligence quotient (IQ) and ROCF recall trial scores were significantly increased postoperatively, whereas there were no postoperative differences in verbal IQ, WMS, and ROCF copy trial scores. State anxiety scores were significantly decreased postoperatively, but there was no change in trait anxiety scores. Furthermore, a significant negative correlation was observed between changes in state anxiety scores and preoperative verbal IQ, performance IQ, and WMS. None of the patients developed postoperative cognitive functional impairments as demonstrated by event-rate analysis., Conclusions: Surgical treatment of UIAs does not impair cognitive function and results in improvement in state anxiety in elderly patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Patients with SAH often experience cognitive decline. Previous studies used normal volunteers, published normal test values, and orthopedic patients as controls to identify factors for postoperative cognitive decline. The present study excluded the effects of surgery by comparing cognitive function after surgical repair in patients with aneurysmal SAH and patients with unruptured intracranial aneurysm., Methods: This study recruited 117 patients with SAH due to ruptured aneurysm and 39 patients with incidentally found unruptured intracranial aneurysms. The cognitive test battery consisted of the Japanese translation of the WAIS-R, the Japanese translation of the WMS, and the recall trial of the ROCF. Postoperative neuropsychological test scores for the patients with SAH and control subjects were compared using group-rate and event-rate analysis. The relationship between clinical variable and postoperative cognitive decline in the patients with SAH was evaluated by univariate analysis using the Mann-Whitney U test or chi(2) test., Results: Group-rate analysis showed that the WAIS-R and ROCF scores were significantly lower in the SAH group than in the control group. Event-rate analysis demonstrated that the incidence of cognitive decline in the patients with SAH (73 [62.4%] of the 117 patients) was significantly higher than that in the control subjects (12 [30.8%] of 39 patients). The Hunt and Hess grade was significantly higher in patients with postoperative cognitive decline., Conclusion: The cognitive function after SAH was significantly correlated with Hunt and Hess grade on admission when using patients with postoperative unruptured intracranial aneurysm as the control group., (Copyright 2009 Elsevier Inc. All rights reserved.)

Proton magnetic resonance spectroscopy, diffusion-weighted axonography, and diffusion tensor tractography in a patient with tumefactive demyelination plaque (TDP) were evaluated for differential diagnosis from glioblastoma. The findings of glutamate and glutamine elevations on magnetic resonance spectroscopy and apparent tracts within the lesion on axonography and tractography were unlikely to represent glioblastoma, and were thus useful for the preoperative diagnosis of TDP.

Recent studies indicate that the balance between cell survival and proapoptotic signals determines which cells commit to life or death. We have shown that the balance between follicle-stimulating hormone and prolactin determines differentiation or apoptosis in 7th generation spermatogonia during newt spermatogenesis; however, the molecular mechanisms specifying their fate are poorly understood. Here we show that the newt RNA-binding protein (nRBP) plays a critical role in determining their fate. nRBP was identified as a clone whose mRNA is decreased by prolactin, resulting in the reduction of the protein, which is otherwise expressed predominantly in the spermatogonia. nRBP protein associated with the mRNA for newt programmed cell death protein 4 (nPdcd4) at the 3'-untranslated region. nRBP reduction increased nPdcd4 mRNA but decreased its protein. In a cell-free system, cytoplasmic extracts containing reduced amounts of nRBP and nPdcd4 protein induced apoptosis, whereas adding nRBP protein to the extracts blocked apoptosis. Furthermore, overexpression of nRBP protected cells from apoptosis, stabilized the chimeric transcript containing the nPdcd4 3'-untranslated region, and accelerated its translation. These data suggest that, in the absence of nRBP, nPdcd4 mRNA is not stabilized and its translation is suppressed, leading to apoptosis in the spermatogonia.

A 48-year-old woman presented with a left cerebellopontine angle mass. Over a 93-month period, the patient underwent seven surgeries, two radiosurgeries, and one external beam radiotherapy. The tumor was histologically benign at the first operation, but exhibited unusually aggressive behavior after failed radiosurgery and demonstrated clinical characteristics of malignancy such as spinal metastasis. The patient underwent gamma knife radiosurgery (GKR) for recurrence after the first operation, despite the tumor being located in a resectable region. The tumor did not respond. Six months after the sixth surgery, the patient presented with progressive lower extremity paraparesis and sensory disturbance below the T11 dermatome. Magnetic resonance imaging revealed multiple intradural mass lesions located at the T2, T11-T12, and L2 levels. She died 4 months after the diagnosis of spinal metastases. Retrospectively, we speculate that if a tumor is located in a resectable region and Simpson grade I or II tumor resection is possible, direct surgery may be a safer option than GKR.

Object: Although angioplasty and stent placement for vertebral artery (VA)-origin stenosis have been performed using endovascular techniques, a high likelihood of restenosis has been observed in the long term. Therefore, the authors assessed the long-term clinical and angiographic outcomes in patients after VA-subclavian artery (SA) transposition., Methods: Thirty-six patients (31 men, 5 women; mean age 64.3 years, range 46-76 years) underwent clinical evaluation (modified Rankin Scale [mRS]) and cervical angiographic evaluation preoperatively and within 1 month of and 6 months after VA-SA transposition undertaken to treat symptomatic stenosis of VA origin., Results: Postoperative neurological deficits due to intraoperative brain ischemia did not occur, and MR imaging demonstrated no new postoperative ischemic lesions in any of the patients. One patient died of acute myocardial infarction 2 months after surgery and another developed a left thalamic hemorrhage (mRS score of 5) at 42 months postsurgery. None of the remaining 34 patients experienced further ischemic events, and the mRS score in all of these patients remained unchanged during a mean follow-up period of 54 months. The degree of VA-origin stenosis (preoperative mean 84%) was reduced to < or = 30% after surgery (mean 2%). Long-term follow-up angiography in 29 patients (81%) revealed the absence of restenosis, defined as > 50% luminal narrowing, in all of them., Conclusions: The clinical and angiographic long-term outcomes demonstrated here suggest that VA-SA transposition will be useful in patients with symptomatic stenosis of VA origin.

This study evaluated the mechanical properties and the surface elemental composition of Yasargil Phynox aneurysm clips implanted for 10 years in a patient with cerebral aneurysm. Two Yasargil Phynox aneurysm clips implanted 10 years previously to treat a ruptured vertebral artery aneurysm were retrieved when the regrown and ruptured aneurysm was repaired with a new aneurysm clip. Two new Yasargil aneurysm clips were used as controls. Measurements of closing force, bending strength, and the elemental composition of the clip surface were performed. The closing force of the retrieved clips was similar or greater compared to the force before implantation. The bending test showed that the elastic limit and 0.2% proof load of the retrieved clip were higher than those of the unused clip, whereas the ultimate load of the retrieved clip was similar to that of the unused clip. The elemental concentration of Cr oxide on the surface of the retrieved clips was almost the same as that on the unused clips. The present study demonstrated that Yasargil Phynox aneurysm clips retain their mechanical properties and surface elemental composition in vivo for a long time, which indicates that Yasargil aneurysm clips will remain reliable in patients for extended periods.

The anteromedial superior cerebellar tumor can be accessed by various routes. For tumor presenting at the cerebellar surface in this region, the optimal approach remains contentious. Furthermore, which of the various routes offers the optimal approach to a tumor that is not present at the cerebellar surface but lies deep anteromedial superior cerebellum is a matter of debate. We report herein the case of a 44-year-old woman with hemangioblastoma deep within the subcortex of the anteromedial superior cerebellum. Preoperative magnetic resonance (MR) imaging and three-dimensional anisotropy contrast MR axonography using diffusion-weighted MR imaging demonstrated that the posterior subtemporal transtentorial (PSTT) approach would provide a shorter surgical corridor, minimal cerebellar split, and better preservation of nerve fibers, compared to the other approaches. Surgical tumor removal was successfully achieved using the PSTT approach. During surgery, the PSTT approach provided an operative field that enabled visualization of the proximal side of the superior cerebellar artery as the tumor feeding vessel. Although the vein of Labbé inserted just into the transverse-sigmoid junction, injury to this vein was avoided using optimal head position, cerebrospinal fluid drainage, and various devices. For patients with tumor located within the subcortex of the anteromedial superior cerebellum, the PSTT approach is recommended as an optimal surgical route. Scrupulous evaluation using preoperative neuroimaging is crucial when deciding on the surgical approach.

A 55-year-old man presented with a rare lipomatous meningioma associated with acute subdural hematoma manifesting as sudden onset of severe headache, but no neurological deficit. No evidence of trauma or underlying predisposition to hemorrhage was seen. Fluid-attenuated inversion-recovery magnetic resonance imaging showed a thin hyperintense area in the right temporal convexity, and an extra-axial mass appearing as mixed hypointensity and hyperintensity. Two weeks later, right temporal craniotomy was performed and the tumor was totally resected with the attached dura. The hematoma was localized at the inferior margin of the mass and connected directly with the tumor. Histological examination of the resected specimen revealed typical meningothelial meningioma admixed with mature adipose tissue. Longstanding intratumoral congestion probably caused hyaline deposition in the tissue, leading to vessel rupture.

A fusion technique for magnetic resonance (MR) angiography and MR imaging was developed to help assess the peritumoral angioarchitecture during surgical planning for meningioma. Three-dimensional time-of-flight (3D-TOF) and 3D-spoiled gradient recalled (SPGR) datasets were obtained from 10 patients with intracranial meningioma, and fused using newly developed volume registration and visualization software. Maximum intensity projection (MIP) images from 3D-TOF MR angiography and axial SPGR MR imaging were displayed at the same time on the monitor. Selecting a vessel on the real-time MIP image indicated the corresponding points on the axial image automatically. Fusion images showed displacement of the anterior cerebral or middle cerebral artery in 7 patients and encasement of the anterior cerebral arteries in 1 patient, with no relationship between the main arterial trunk and tumor in 2 patients. Fusion of MR angiography and MR imaging can clarify relationships between the intracranial vasculature and meningioma, and may be helpful for surgical planning for meningioma.

Background: The purpose of the present study was to investigate the relationship between serum concentrations of the immunoglobulin-like superfamily, selectins, hsCRP, and the development of DIND in patients with aneurysmal SAH., Methods: Serum ICAM-1, VCAM-1, E-selectin, P-selectin, L-selectin, and hsCRP were measured in 33 patients with SAH who underwent aneurysmal clipping within 48 hours of the onset of symptoms. Serum samples were obtained during the early period (day 0) and the late period (day 7)., Results: The serum concentrations of ICAM-1 (P = .009), VCAM-1 (P = .0383) and hsCRP (P = .0014) during the early period were significantly higher in patients with SAH than in control patients. Further, serum hsCRP concentration during the late period was significantly higher in patients with SAH than in control patients (P = 0033). Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND., Conclusions: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND.

A technique for exposing the vertebrobasilar junction with traction of the dentate ligament is described for treatment of large vertebral artery (VA) aneurysms via the far lateral suboccipital approach with partial condylar resection. The most rostral attachment of the dentate ligament is divided above the site where the VA pierces the dura mater. A traction suture is placed into the dentate ligament and gently retracted using mosquito forceps. As a result, the medulla oblongata is lifted dorsally and slightly rotated by the divided and retracted dentate ligament, allowing an approach from a more superior or inferior direction. The present technique is useful for the treatment of large thrombosed VA aneurysms.

Wide exposure of lesions during the subtemporal approach often leads to temporal lobe injury caused by excessive retraction. A brain retraction technique using gelatin sponge pieces was developed to minimize intraoperative brain retraction during the subtemporal approach. After aspirating cerebrospinal fluid and slackening the temporal lobe, 2-3 pieces of gelatin sponge are inserted between the dura and surfaces of the anterior and posterior parts of the temporal lobe, then covered with cottonoids. The gelatin sponge pieces expand and thus expose the free margin of the tentorium with minimal brain retraction. This technique was used in 50 patients undergoing clipping for cerebral aneurysms. Although computed tomography indicated minor brain injury caused by retraction in three patients with ruptured aneurysm of the basilar artery bifurcation, no patients experienced new neurological deficits other than transient ipsilateral oculomotor nerve paresis. In conclusion, gelatin sponge, with its innate mechanical characteristics and ease of application, seems to offer an alternative retractor in neurosurgical interventions using the subtemporal approach for patients with unruptured aneurysm or non-severe subarachnoid hemorrhage.

Background: Symptomatic atherosclerotic steno-occlusive diseases of the vertebrobasilar artery portend a poor prognosis and high risk of stroke recurrence despite medical therapy. We describe 5 medically refractory patients with occlusion at the origin of the VA and the distal portion of the cervical VA perfused via muscular collateral vessels who underwent ECA-cervical VA (V(2) segment) bypass with interposed SVG., Methods: The ECA was isolated through a linear incision along the anterior portion of the sternocleidomastoid muscles. The ECA was either laterally or medially retracted, the longus colli muscle was dissected, and the anterior wall of the foramen transversarium was partially removed, which exposed the cervical VA. Each end of the SVG was anastomosed to both the VA and the ECA in a side-to-end fashion., Results: Surgery proceeded smoothly in all patients without any new neurologic postoperative deficits. Postoperative cerebral angiography demonstrated that the anastomosis was patent. None of the patients developed further brain ischemic events during follow-up periods ranging from 13 to 114 months (mean, 62 months) after surgery., Conclusion: The ECA-cervical VA bypass with interposed SVG is useful when the VA is occluded at the origin and when the distal portion of the cervical VA is perfused via muscular collateral vessels of patients with medically refractory ischemic events in the vertebrobasilar territory.

Background: Adrenomedullin (AM), a vasorelaxant peptide, is secreted into the cerebrospinal fluid (CSF) from the choroid plexus and can exert natriuretic effects in the kidney. CSF AM concentration is elevated 7-10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentrations correlate with hyponatremia and delayed ischemic neurological deficits (DIND) after SAH., Methods: CSF and plasma concentrations of AM, brain natriuretic peptide, and atrial natriuretic peptide concentrations were measured in 32 patients with SAH who underwent aneurysmal clipping within 48 h of onset. CSF and blood samples were obtained from these patients during the early period (days 1-3, day 0 being regarded as the day of SAH onset) and the late period (days 8-10)., Results: In all patients, AM concentration during the early and late periods was significantly higher in the CSF than in the plasma (p = 0.0028 and p < 0.0001). In addition, CSF AM concentration was significantly higher during the late period than during the early period (p < 0.0001). Hyponatremia (plasma sodium <135 mmol/l) was present in 11 patients (34.4%) during the late period, and DIND developed in 6 patients (19%) between day 5 and day 13. Logistic regression analysis demonstrated that late-period CSF AM concentration correlated with hyponatremia and DIND (95% CI: 1.003-1.069, p = 0.0074 and 95% CI: 1.003-1.052, p = 0.0108)., Conclusions: The present study demonstrated that CSF AM during the late period following SAH correlates with hyponatremia and DIND., ((c) 2008 S. Karger AG, Basel.)

A technique is described for removing previously placed aneurysm clips and applying new aneurysm clips for the treatment of regrown or reruptured cerebral aneurysms in patients more than 10 years after the original clipping of the aneurysm neck. The adherent tissue covering previously placed clips is cut just on and alongside the clips themselves using a small scalpel. Using the clip applicator, gentle pressure is applied to open the clip blade as little as possible. The aneurysm clip is carefully slid out along the line where the clip blade has resided, and a new aneurysm clip is applied. The procedure was successfully accomplished in four patients. Whereas three of these patients had an uneventful postoperative course, the remaining patient experienced transient right oculomotor nerve palsy and left-sided motor weakness. The present technique is a useful procedure for treatment of regrown or reruptured cerebral aneurysms occurring a significantly long time after initial clipping of an aneurysm neck.

Object: Preoperative planning for meningiomas requires information about tumor consistency as well as location and size. In the present study the authors aimed to determine whether the fractional anisotropy (FA) value calculated on the basis of preoperative magnetic resonance (MR) diffusion tensor (DT) imaging could predict meningioma consistency., Methods: In 29 patients with intracranial meningiomas, MR DT imaging was performed preoperatively, and the FA values of the tumors were calculated. Tumor consistency was intraoperatively determined as hard or soft, and the histological diagnosis of the tumor was established., Results: Of the 29 tumors, 11 were classified as hard and 18 as soft. The FA values of fibroblastic meningiomas were significantly higher than those of meningothelial meningiomas (p = 0.002). The FA values of hard tumors were significantly higher than those of soft tumors (p = 0.0003). Logistic regression analysis demonstrated that the FA value was a significant independent predictor of tumor consistency (p = 0.007)., Conclusions: The FA value calculated from preoperative MR DT imaging predicts meningioma consistency.

Background/aims: We have performed ileocolon interposition for reconstruction (IR) after total gastrectomy in order to reduce postoperative symptoms such as heartburn, reflux esophagitis and nutritional disturbance. After IR, however, the frequency of diarrhea increased in the postoperative period. We therefore investigated whether post-IR diarrhea could be prevented by preserving the vagus nerve., Methodology: The vagus nerve was not preserved in 46 (non-PV group) stage I and II gastric cancer patients treated with the IR method, and preserved in 28 for stage IA (PV group). By means of a mailed and interviewed questionnaire, we surveyed the patients at six months postoperatively to examine how diarrhea had occurred in either group., Results: The frequency of diarrhea of the PV group was as low as 26% (7/27) which was significantly lower than 76% (35/46) of the non-PV group., Conclusions: Preservation of the vagus nerve during reconstruction using ileocolon interposition after total gastrectomy for stage IA is a superior approach for the prevention of postoperative diarrhea.

Neck clipping for internal carotid-posterior communicating artery (IC-PC) aneurysms using standard straight, angled, or curved clip may result in remnant aneurysm neck. We describe complete neck clipping of IC-PC aneurysms using a bayonet-shaped clip. The bayonet-shaped clip is applied perpendicular to the long axis of the internal carotid artery (ICA), and the blades of the clip are inserted between the aneurysm neck and the ICA. Using the clip applicator, the clip is gradually rotated counterclockwise or clockwise for left or right ICA aneurysm, respectively, so that the distal and shank portions of the clip blade are located at the aneurysm neck in the posterior communicating artery (Pcom) and ICA, respectively. As a result, the distal flexure of the clip blade fits the junction of the ICA and Pcom. This technique was used in four patients with ruptured ICA aneurysms and five patients with unruptured ICA aneurysms. Postoperative cerebral angiography demonstrated no residual aneurysm neck and preservation of the Pcom in all patients. This technique is useful for cases of IC-PC aneurysm involving the origin of the Pcom.

Background: Magnetic resonance imaging can provide a preoperative diagnosis of pontine glioma, but the findings sometimes do not correspond with the clinical symptoms. We describe 2 cases of pontine gliomas who did not present with motor and sensory disturbance., Case Report: Three-dimensional anisotropy contrast (3DAC) imaging was used to assess the neuronal tracts in 2 patients with pontine gliomas. Conventional MR imaging depicted markedly abnormal findings of abnormally high or heterogeneous signal intensity in the pons in 2 cases. In contrast, 3DAC imaging obviously showed the corticospinal and spinothalamic tracts and cerebellar peduncles without destruction by tumors., Conclusion: Three-dimensional anisotropy contrast imaging provides more information about damage to the neuronal tracts in cases of pontine gliomas than other MR imaging techniques. This technique may be used for preoperative mapping of the tumor and its relationship to the tracts, thus, providing an accurate road map for tumor resection.

A 72-year-old woman presented with meningothelial meningioma causing obstruction of the superior sagittal sinus (SSS). Magnetic resonance imaging demonstrated the lesion in the left occipital parasagittal region and a linear vascular structure in the posterior falx extending from the vein of Galen to the SSS. Cerebral angiography demonstrated obstruction of the posterior portion of the SSS and venous flow from the bilateral occipital lobes draining into the falcine sinus and then into the vein of Galen. The tumor was subtotally removed with preservation of the falcine sinus and bridging veins draining into the sinus. The falcine sinus is usually obliterated after birth, but may persist into adulthood and be involved in unusual draining patterns.

Fractional anisotropy (FA) is influenced by histological data such as cellularity, vascularity and/or fiber structure in astrocytic tumors. We describe two patients with tumor recurrence and one patient with radiation necrosis who were diagnosed using assessment of FA value. The assessment of FA value in enhanced lesions after radiotherapy may be able to differentiate radiation necrosis from tumor recurrence.

A 65-year-old woman presented with subarachnoid hemorrhage (SAH). Angiography detected a small bulge in the A1 segment of the right anterior cerebral artery (ACA). The patient was managed conservatively. Ten days after the initial SAH, the patient suffered a second SAH. Cerebral angiography demonstrated a fusiform aneurysm in the right A1 segment and vasospasm in the left A1 segment. The aneurysm of the right A1 segment was trapped and the right superficial temporal artery (STA) was end-to-end anastomosed to the distal portion of the right A1 segment. The patient had no postoperative cerebral ischemic events. Postoperative cerebral angiography revealed that the bypass flow through the right STA perfused the right ACA territories. STA-A1 end-to-end anastomosis can prevent cerebral ischemic events following parent vessel occlusion or microsurgical trapping for fusiform cerebral aneurysms in the A1 segment without sufficient collateral flow to the ipsilateral ACA territory from the contralateral ACA.

Lentinan (LNT) is a beta-glucan known to have a life-prolonging effect in combination with chemotherapy for patients with unresectable or recurrent gastric cancer. Thus, a multi-center trial of chemo-immunotherapy using S-1 combined with LNT may benefit patients with unresectable or recurrent gastric cancer with acceptable toxicity. With such a regimen, the median survival time in 32 patients was 559 days. Regardless of change to second-line chemotherapy, the mean period of using S-1+LNT for patients with long NC above 400 days was 725 days. In subset analyses, the survival period of the patients with G/L ratio of equal to or less than 2 was significantly better than that of the higher one (p<0.0001). The incidence of hematological toxicity (grade 3 leukopenia and thrombocytopenia) was 6.3% (2/32), and non-hematological toxicity (grade 2 dysgeusia) was 6.3% (2/32), while no grade 4 toxicity was observed. S-1 and LNT combination immunotherapy was carried out safely with high QOL and allowed a prolonged administration. S-1+LNT regimen may prolong NC periods in patients with unresectable or recurrent gastric cancer.

A 76-year-old man with an abdominal aortic aneurysm (AAA) initially presented with ischemic colitis, which was improved by conservative treatment. Preoperative assessment by computerized axial tomography scanning and aortography revealed an infrarenal type AAA with mural thrombus, stenoses of the right common iliac artery and the left internal iliac artery. The patient underwent aortoiliac bypass surgery with resection of the stenoses, and reconstruction of the left internal iliac artery. No complications including bowel ischemia, were noted postoperatively. This case emphasized the potential benefits of the extraperitoneal approach to the aorta, reconstruction of both internal iliac arteries, and use of prostaglandin E1.

Objective and Importance: We describe a case of brainstem cavernous angioma resected by the subtemporal, anterior transpetrosal approach, selected on the basis of three-dimensional anisotropy contrast (3-DAC) imaging., Clinical Presentation: A 64-year-old woman presented with sudden headache and gait disturbance. Anatomic magnetic resonance imaging showed a mass lesion in the left anterolateral part of the pons. On 3-DAC imaging, posteromedial compression of the left corticospinal and corticopontine tracts by the mass lesion was demonstrated., Intervention: The lesion was resected through the anterolateral side of the pons via the subtemporal, anterior transpetrosal approach. Neurological symptoms improved postoperatively, and postoperative 3-DAC imaging demonstrated preservation of the corticospinal and corticopontine tracts., Conclusion: The technique of 3-DAC imaging may provide important information regarding neural tracts for the planning of brainstem surgery.

A 57-year-old man with gastrointestinal stromal tumor (GIST) of the stomach with peritoneal dissemination underwent gastrectomy. After surgery, he was treated with 400 mg/day of imatinib, without recurrence, for 26 months. At 26 months, the imatinib dose was reduced because of nausea, and 4 months after the dose reduction, recurrence of GIST was detected, for which surgical resection was performed again. The first surgical specimen had a mutation of exon 11 in the c-kit receptor gene. Intriguingly, the second surgical specimen had a novel mutation of exon 17, in addition to the above-mentioned mutation, in the c-kit receptor gene. Based on the result of molecular analysis, the novel mutation of exon 17, induced by longterm chemotherapy, was judged to have been responsible for the recurrence, which perhaps was triggered by the dose reduction of imatinib.

Objective and Importance: We describe a case of brainstem cavernous angioma in which the neural tracts were evaluated before surgery by three-dimensional anisotropy contrast (3-DAC) magnetic resonance imaging., Clinical Presentation: A 64-year-old man presented with a cavernous angioma located intrinsically in the brainstem and manifesting as gait ataxia. 3-DAC imaging demonstrated that the lesion was located outside the left inferior cerebellar peduncle and inside the middle cerebellar peduncle., Intervention: The intact brain surface was incised, and the lesion was removed successfully on the basis of the preoperative 3-DAC images. The patient exhibited temporary exacerbation of his gait ataxia, but the symptom improved 3 months after surgery. Postoperative 3-DAC imaging demonstrated resection of the lesion and preservation of the left inferior and middle cerebellar peduncles., Conclusion: 3-DAC imaging may provide essential information about the neural tracts for the planning of brainstem surgery.

Background:  Various types of classification of gastritis have been proposed, but no plausible classification has been available until now. The Research Society for Gastritis performed a pilot study to establish an endoscopic classification, taking into consideration the following: (i) ease of use; (ii) permitting everyone the common image; and (iii) presence of histopathological evidence., Methods:  One hundred and fifty-five patients were enrolled and underwent gastroscopy. Eight basic endoscopic and histological types of gastritis (superficial, hemorrhagic, erosive, verrucous, atrophic, metaplastic, hyperplastic and special types) were defined. Gastritis was endoscopically diagnosed according to the definition of the endoscopic types of gastritis. Four or more biopsy specimens were obtained from the lesser and the greater curvatures of the antrum and the corpus of each patient, and the histological findings of gastritis and Helicobacter pylori infection were assessed. The histological diagnosis of gastritis was made according to the definition of histology types of gastritis. The endoscopic and the histological diagnoses were then compared in a blinded fashion., Results:  Endoscopic diagnosis was 62% as sensitive as histological diagnosis for erosive gastritis, 67% for verrucous gastritis and 84% for atrophic gastritis in the antrum. In superficial gastritis, sensitivity was approximately 25% in the corpus, but only 8% in the antrum. Metaplastic and hyperplastic gastritis were correctly diagnosed only in severe cases., Conclusion:  Five basic types of gastritis (superficial, erosive, verrucous, atrophic and special types) should be employed for the new endoscopic gastritis classification. Metaplastic and hyperplastic gastritis are considered to be subtypes of atrophic gastritis and they should be excluded from the basic endoscopic classification. A new definition of gastritis in the antrum accompanied by redness still remains to be investigated.

Background: Telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA, is thought to be necessary for cellular immortality and carcinogenesis. Telomerase activity is associated with the majority of malignant human cancers. The mRNA that encodes the telomerase catalytic subunit (human telomerase repeat transcriptase; hTERT) has recently been identified, and the expression of the hTERT gene is thought to regulate the activation of telomerase. However, the expression of hTERT mRNA in esophageal tissues has not been reported. We investigated hTERT gene expression in cancerous and noncancerous esophageal tissues, and determined the relationship between hTERT mRNA expression and telomerase activity., Methods: Tissues from esophageal carcinomas in 14 patients, reflux esophagitis in 12 patients, esophageal acanthosis in 2 patients, esophageal papilloma in 1 patient, radiation esophagitis in 1 patient, and normal esophageal epithelium in 11 patients (including 3 specimens of normal epithelium from patients with esophageal carcinoma) were examined. All specimens were taken endoscopically. hTERT gene expression was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Quantitative analysis of telomerase activity was analyzed by fluorescence telomeric repeat amplification protocol (F-TRAP) assay., Results: Thirteen of the 14 (93%) esophageal carcinoma specimens expressed hTERT mRNA and revealed detectable telomerase activity. Noncancerous esophageal lesions had not only hTERT mRNA expression with a high frequency (14 of 16 cases; 88%) but also detectable telomerase activity (12 of 13 cases; 92%). Normal esophageal epithelium also highly expressed hTERT mRNA (10 of 11 cases; 91%) and revealed detectable telomerase activity (all 9 cases; 100%). In 32 of the 35 specimens analyzed for both hTERT mRNA and telomerase activity (91%), the expression of hTERT mRNA was consistent with detectable telomerase activity., Conclusions: The expression of hTERT mRNA was detected not only in cancerous but also in noncancerous esophageal tissues at a high frequency. This result was different from that reported for other gastrointestinal epithelium. Moreover, telomerase activity in esophageal carcinoma was significantly stronger than that in reflux esophagitis and normal epithelium. In addition, there was a strong relation ship between the detection of telomerase activity and the expression of hTERT mRNA in cancerous and noncancerous esophageal tissues. Thus, the qualitative analysis of hTERT mRNA expression may not be useful as a biomarker of carcinoma in esophageal tissues. Nevertheless, the quantitative analysis of telomerase activity may be somewhat useful.

Background: The superficial spreading type of gastric carcinoma may originate from either a single cellular clone or from several different clones; this issue remains controversial. Indeed, the p53 gene has been shown to play an important role in gastric carcinogenesis, but there have been only a few reports on the heterogeneity of gastric carcinoma with respect to the p53 gene., Methods: We analyzed seven cases of the superficial spreading type of gastric submucosal carcinomas (80 lesions; 10 to 17 per case) which showed different histological types and/or different p53 protein staining patterns. Direct sequences of polymerase chain reaction products were used for the analysis., Results: p53 Gene heterogeneity in mucosal carcinoma lesions was detected in three cases. However, in all of the cases, the p53 mutational pattern was identical to that found in the submucosal carcinoma lesions. In the heterogeneous cases, the mutation in the submucosal carcinoma was one of the mutation patterns found among the mucosal carcinoma lesions. More precisely, the mutational pattern of both submucosal carcinoma lesions and the mucosal lesions located just above them, was identical., Conclusion: These data suggest that, with regard to the p53 gene, in some superficial spreading types of gastric carcinomas, there are various subclones in the mucosal carcinoma; one of these subclones becomes predominant through clonal selection, and, thus, invades the submucosa.

Background and Aims: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia., Methods: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol., Results: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P=0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA., Conclusions: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.

Background: Antimicrobial susceptibility testing of Helicobacter pylori isolates is the most useful tool for guiding specific therapy, especially when primary resistance is suspected. However, the most informative gastric biopsy site for detection of resistant H. pylori isolates is uncertain. We sought to determine whether susceptibilities to commonly used antimicrobials (amoxicillin, clarithromycin, minocycline, and metronidazole) were related to biopsy site., Methods: H. pylori isolates were obtained from patients who had duodenal ulcer and had not received any therapy directed against H. pylori. Agar-dilution minimum inhibitory concentrations of each antimicrobial were compared between paired H. pylori isolates from the antrum and the proximal corpus., Results: Differences in minimum inhibitory concentrations exceeding twofold were observed within the pairs of H. pylori isolates in 5 of the 40 patients tested. In three patients with clarithromycin-resistant isolates and two with metronidazole-resistant isolates, both antral and corporeal specimens revealed resistance. However, no patient had pairs of isolates categorized as resistant at one site and sensitive at the other., Conclusions: While we found that an individual may have a mixed H. pylori infection with respect to differing antimicrobial susceptibility in different parts of the stomach, a single biopsy specimen from either the antrum or the corpus should provide reliable detection of H. pylori isolates with primary resistance.