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BACKGROUND Hemifacial spasm (HFS) is caused by neurovascular contact along the facial nerve’s root exit zone (REZ). The authors report a rare HFS case that was associated with ipsilateral subclavian steal syndrome (SSS). OBSERVATIONS A 42-year-old man with right-sided aortic arch presented with progressing left HFS, which was associated with ipsilateral SSS due to severe stenosis of the left brachiocephalic trunk. Magnetic resonance imaging showed contact between the left REZ and vertebral artery (VA), which had shifted to the left. The authors speculated that the severe stenosis at the left brachiocephalic trunk resulted in the left VA’s deviation, which was the underlying cause of the HFS. The authors performed percutaneous angioplasty (PTA) to dilate the left brachiocephalic trunk. Ischemic symptoms of the left arm improved after PTA, but the HFS remained unchanged. A computational fluid dynamics study showed that the high wall shear stress (WSS) around the site of neurovascular contact decreased after PTA. In contrast, pressure at the point of neurovascular contact increased after PTA. LESSONS SSS is rarely associated with HFS. Endovascular treatment for SSS reduced WSS of the neurovascular contact but increased theoretical pressure of the neurovascular contact. Physical release of the neurovascular contact is the best treatment option for HFS.

Background Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases. Objective To apply a novel treatment method, convection-enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead to remarkable regression of enlarging tumors that are, otherwise, difficult to control. Methods Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemotherapy and radiotherapy induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord at 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan. Results After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms, including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the 2 patients were as long as 67 and 33 mo. Conclusion The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC, especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

Background The management of intracranial aneurysm (IA) is challenging. Clinicians often rely on varied and intuitively disparate ways of evaluating rupture risk that may only partially take into account complex hemodynamic and morphologic factors. We developed a prototype of a clinically oriented, streamlined, computational platform, AView, for rapid assessment of hemodynamics and morphometrics in clinical settings. To show the potential clinical utility of AView, we report our initial multicenter experience highlighting the possible advantages of morphologic and hemodynamic analysis of IAs. Methods AView software was deployed across 8 medical centers (6 in the United States, 2 in Japan). Eight clinicians were trained and used the AView software between September 2012 and January 2013. Results We present 12 illustrative cases that show the potential clinical utility of AView. For all, morphology and hemodynamics, flow visualization, and rupture resemblance score (a surrogate for rupture risk) were provided. In 3 cases, AView could confirm the clinicians' decision to treat; in 3 cases, it could suggest which aneurysms may be at greater risk among multiple aneurysms; in 5 cases, AView could provide additional information for use during treatment decisions for ambiguous situations. In one stent-assisted coiling case, flow visualization predicted that the intuitive choice for stent placement could have resulted in sacrifice of an anterior cerebral artery due to blockage by coils and led clinicians to reconsider treatment plans. Conclusions AView has the potential to confirm decisions to treat IAs, suggest which among multiple aneurysms to treat, and guide treatment decisions. Furthermore, the flow visualization it affords can inform aneurysm treatment planning and potentially avoid poor outcomes.

Background: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. Methods: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. Results: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. Conclusions: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients.

We thank Hu and Wang for their interest in our study. We also think that the use of a stent to assist coil embolization alters the bifurcation angle in an upward direction, which …

Escherichia coli PhoB protein is the transcriptional activator of the phosphate (pho) regulon genes involved in phosphate utilization. To gain further insight into the potential roles of PhoB in the phosphate starvation response, we attempted to identify PhoB-regulated promoters using a random shotgun library of E. coli O157:H7 genomic fragments that were fused to a promoterless lacZ reporter gene on a low-copy-number plasmid. Using this approach, numerous chromosomal regions containing phosphate-starvation-inducible (psi) promoters, including nearly all known pho regulon promoters, were identified. β-Galactosidase and electrophoretic mobility shift assays showed that transcription from the 22 identified psi promoters was directly regulated by PhoB. PhoB-binding sites within the promoter regions were identified by DNase I footprinting. The genes for yoaI, rpsG, galP, rnr, udp, sstT, ybiM, and vgrE were located downstream of these promoters, indicating that these genes are members of the pho regulon. Surprisingly, the other 14 promoters were located within sense or antisense strands of open reading frames (ORFs), and/or at a distance from ORFs. Our results suggest that PhoB has broader roles in gene regulation and RNA expression in E. coli strains than was previously supposed. Our shotgun-library cloning approach represents a powerful tool for identifying promoters activated or repressed by transcriptional regulators that respond to environmental stimuli.

To introduce porphyrins such as the alcoholic-hydroxyl-group-appended free base porphyrin derivative (HP) of 5-[4-(3-hydroxylpropyloxycabonyl)phenyl]-10,15,20-triphenylphorphine into mesopores of MCM-41, samples were treated with 0-4.0 mmol dm-3 HP toluene solutions and the materials obtained were characterized by various means. The framework structure of MCM-41 was not altered by the treatment. With increasing HP concentration, the specific surface area and pore size decreased; in contrast, the number of HP molecules in the material increased almost linearly from 0 to 0.17 groups nm-2. These facts reveal that the HP molecules are incorporated into mesopores of MCM-41. IR results indicated that the hydroxyl group of the HP molecule reacts with surface free SiOH groups of the MCM-41 by a dehydration reaction. Diffuse reflection UV-vis spectra of the HP-introduced material were almost the same as that of pure HP molecules. The Beers plot suggested that the HP molecules in the material are dispersed at an HP concentration less than 1.0 mmol dm-3, and above that concentration, aggregation or flattening of the HP molecules on the MCM-41 surface takes place.

POB1 was previously identified as a RalBP1-binding protein. POB1 and RalBP1 function downstream of small G protein Ral and regulate receptor-mediated endocytosis. To look for additional functions of POB1, we screened for POB1-binding proteins using a yeast two-hybrid method and found that POB1 interacts with mouse ASAP1, which is a human PAG2 homolog. PAG2 is a paxillin-associated protein with ADP-ribosylation factor GTPase-activating protein activity. POB1 formed a complex with PAG2 in intact cells. The carboxyl-terminal region containing the proline-rich motifs of POB1 directly bound to the carboxyl-terminal region including the SH3 domain of PAG2. Substitutions of Pro(423) and Pro(426) with Ala (POB1(PA)) impaired the binding of POB1 to PAG2. Expression of PAG2 inhibited fibronectin-dependent migration and paxillin recruitment to focal contacts of CHO-IR cells. Co-expression with POB1 but not with POB1(PA) suppressed the inhibitory action of PAG2 on cell migration and paxillin localization. These results suggest that POB1 interacts with PAG2 through its proline-rich motif, thereby regulating cell migration.

Background Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients’ growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission. Methods In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11–19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. Results Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8–17, and the average endoscopic index was 8.5 ± 1.5, range 7–11. The corresponding values at week 12 were 2.1 ± 0.2, range 1–4 (P

Using a hydroxyl group appended free base porphyrin derivative (HP), porphyrin-introduced silica gels were synthesized by a sol-gel process. The HP content in the materials linearly increased with increasing the HP concentration. Meanwhile, free base tetraphenylporphyrin (TPP) with no hydroxyl groups were almost not incorporated into the silica gels. These facts suggested that the interaction between hydroxyl groups of the HP molecules and silica network is considerably strong. The UV-vis characters of HP-introduced materials were almost the same as pure HP molecules. The Beer's plot indicated that the HP molecules in the materials are dispersed.

Objective: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. Design: Descriptive, controlled study. Setting: Tohoku University School of Medicine. Patient(s): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. Intervention(s): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. Main Outcome Measure(s): Immunostaining. Result(s): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. Conclusion(s): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.