Detection of current-sheet and bipolar ion flows in a self-generated antiparallel magnetic field of laser-produced plasmas for magnetic reconnection research.

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

Sandwich ELISA Using a Mouse/Human Chimeric CSLEX-1 Antibody.

BACKGROUND: An assay using a mouse antisialyl Lewis X (sLeX) antibody (CSLEX-1) is used clinically for screening and monitoring patients with breast cancer in Japan. However, the IgM isoform of CSLEX-1 is not preferred for the assay because the bulkiness of IgM generally causes poor accessibility to the antigen. To solve this problem, we developed an antisLeX mouse/human chimeric IgG antibody, CH-CSLEX-1, using transgenic silkworms. The performance of a homologous sandwich ELISA of CH-CSLEX1 was then evaluated. METHODS: To generate CH-CSLEX-1, we used a GAL4/UAS binary gene expression system in transgenic silkworms. The reactivities of CSLEX-1 and CH-CSLEX-1 were determined in a Biacore analysis. To confirm antigen specificity, 3 antigens [sLeX, sLeA, and Lewis Y (LeY)] were used. RESULTS: CH-CSLEX-1 formed correctly as an IgG class of immunoglobulin molecule with an isoelectric point close to the predicted value. The best combination for capturing and probing in a sandwich ELISA was determined as a homologous combination of CH-CSLEX-1. The CH-CSLEX-1 assay specifically detected sLeX, but not sLeA and LeY. A correlation analysis with 107 human samples showed good concordance between the conventional CSLEX-1 assay (homologous sandwich ELISA using CSLEX-1) and the CH-CSLEX-1 assay (r = 0.98). Moreover, the CH-CSLEX-1 assay was not affected by either human antimouse IgG antibodies (HAMA IgG) or HAMA IgM. CONCLUSIONS: The mouse/human chimeric antibody CH-CSLEX-1 allowed the establishment of a highly specific sandwich ELISA for sLeX that was not affected by HAMA.

siRNA-lipid nanoparticles with long-term storage stability facilitate potent gene-silencing in vivo.

Considerable efforts have been directed towards discovering and developing delivery vehicles for RNA therapeutics. While most studies emphasize the efficacy and safety of these delivery vehicles, few reports conduct a comprehensive assessment of their storage stability, a critical property for practical applications. Here, we report a potent and safe lipid nanoparticle with long-term storage stability. Through chemical synthesis and screening of cationic lipids, a formulation has been identified that enables potent knockdown of hepatocyte proteins in mice upon intravenous administration (siRNA ED50 ~0.02 mg/kg). Toxicity studies revealed that a dose of 2mg/kg was well tolerated in rats, the most sensitive rodent model. We identified that a cyclic chemical structure in cationic lipids improved particle stability. The nanoparticles showed over 1.5 year storage stability as a liquid, with over 90% siRNA encapsulation without any changes in particle size. This novel delivery material has promising potential as a drug product that could bring RNA therapeutics to the treatment of liver-related disorders.

Cerebral hemodynamic benefits after contralateral carotid artery stenting in patients with internal carotid artery occlusion.

CEA contralateral to an ICA occlusion is considered a surgical risk, and CAS may be an alternative for these patients. Our goal was to examine whether CAS improves cerebral hemodynamics on the treated side and on the side of the ICA occlusion, on the basis of measurement of CBF and CVR by using SPECT. The subjects were 8 patients who underwent contralateral CAS. Resting CBF and CVR to acetazolamide were measured by using (123)I-IMP SPECT before and chronically (3-6 months) after CAS. Resting CBF was also measured immediately (<2 hours) after CAS by using (123)I-IMP SPECT. There were no significant differences in resting CBF in both hemispheres immediately after CAS. However, resting CBF and CVR both significantly increased in the chronic period in both hemispheres. Contralateral CAS in patients with ICA occlusion resulted in cerebral hemodynamic improvement on the treated side and on the side of ICA occlusion.

Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

BACKGROUND: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. METHODS: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. RESULTS: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. CONCLUSION: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.

Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers.

BACKGROUND: We established the cell cycle profiling (C2P) assay for specific activity (SA; activity/expression) of cyclin-dependent kinases (CDKs). C2P risk score (C2P-RS) based on CDK1 and CDK2 SAs was significantly associated with relapse in breast cancer (BC). This study was conducted to investigate the predictive value of C2P-RS for neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Among 124 eligible patients, 122 were treated with weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide (P-FEC) and 2 were treated with paclitaxel monotherapy. C2P-RS was determined via C2P using frozen biopsy samples before NAC. RESULTS: Negative estrogen receptor (ER), negative progesterone receptor (PR), positive human epidermal growth factor receptor 2 (HER2), high Ki-67 expression and intermediate + high C2P-RS were significantly associated with high pathological complete response (pCR) rates compared with positive ER (30% versus 9%), positive PR (25% versus 6%), negative HER2 (34% versus 11%), low Ki-67 expression (24% versus 7%) or low C2P-RS (24% versus 9%), respectively. The combination of C2P-RS and Ki-67 had a stronger impact on pCR than each parameter alone, and a multivariate analysis showed that the combination was an independent predictor of pCR (odds ratio 3.3, 95% confidence interval 1.1-9.5). CONCLUSIONS: C2P-RS was significantly associated with pCR after P-FEC and may be a useful predictor for chemotherapy in BCs.

Combination of rare right arterial variation with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. A case report.

A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed.

Endovascular treatment of a vertebral artery aneurysm via puncture of the surgically exposed vertebral artery.

We describe a case of subarachnoid hemorrhage due to a ruptured right vertebral artery (VA) aneurysm where endovascular therapy via a trans-femoral route was not feasible. Therefore we surgically exposed the VA and directly punctured it at the C4 level, followed by successful coil embolization. Direct access to the vertebral artery using an anterior surgical approach is an alternative in cases where the proximal side of the artery is occluded.

Development of indirect cavernous dural arteriovenous fistula after trapping for direct carotid cavernous fistula. A case report.

SUMMARY: A 60-year-old man with direct carotid cavernous fistula (CCF) due to a motor vehicle accident underwent internal carotid artery trapping following high-flow external carotid to internal carotid artery bypass (EC-IC bypass). Follow-up angiography revealed ipsilateral complex indirect cavernous arteriovenous fistula. Although the traumatic indirect CCF angioarchitecture differs from cavernous-sinus dural arteriovenous fistula (CS-DAVF), the present indirect fistula was similar to the latter. Complex indirect CCF can occur after treatment of direct CCF caused by severe head injury.

Frequency and risk factors for sepsis resulting from neuroendovascular treatment.

OBJECTIVE: Endovascular treatments are minimally invasive and rarely cause complicating infections. Although cases complicated by device infections have been reported, we could not find any studies evaluating infections following neuroendovascular treatment in particular. Therefore, we assessed the frequency of sepsis and other associated risk factors. METHODS: From September 2006 to May 2008, we investigated 256 prospective neuroendovascular treatment cases at our facility. We examined the frequency of sepsis and other associated risk factors as well as organisms and the early detection tests such as various cultures and serodiagnoses. RESULTS: The rate of sepsis due to complications was 8.6% in the aggregate and 5.7% in 193 procedures without a central venous catheter and hemodialysis. All sepsis cases were successfully treated with antibiotics. However, in 2 cases, the patients developed methicillin-resistant STAPHYLOCOCCUS AUREUS infections, which were intractable. The highest risk factors for sepsis were a large sheath size [>7 F; OR =5.03; P =0.01; 95% confidence interval (CI) 1.29-19.47] and meningioma embolization (OR =13.25; P =0.04; 95% CI 1.07-163.56). The degree to which experienced staff (OR =0.09; P =0.05; 95% CI 0.09-0.97) affected the incidence of sepsis was less significant. Microorganisms were isolated from half the operating field, and the risk factor, in this case, depended on inexperienced surgical staff (OR =1.98; P =0.03; 95% CI 1.07-3.67). Although we were unable to find a means to predict sepsis, we presumed antibiotic prophylaxis would be useful. CONCLUSIONS: The frequency of sepsis following neuroendovascular treatment is high. We should pay particular attention to the sterilization process and the operating field when undertaking neuroendovascular treatment that requires the use of a large-size sheath in patients with serious conditions.

Endoscopic submucosal dissection for colorectal tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a state-of-the-art method that enables resection of larger tumors than those resectable by conventional endoscopic mucosal resection (EMR). However, the individual role of each method in the treatment of colorectal tumors remains undetermined. OBJECTIVE AND METHODS: To consider the respective indications of ESD and EMR for colorectal tumors, we analyzed the results of the two treatments retrospectively. RESULTS: Tumors treated by ESD (44 tumors) were significantly larger, more often located in the rectum and more often coexistent with cancer than those treated by EMR (512 tumors). EMR was used in the majority of adenomas, and showed high rates of both one-piece resection (OPR) and complete resection (CR) for adenomas less than 20 mm. However, for adenomas and cancers greater or equal to 20 mm, the CR rate for EMR was significantly lower than that for ESD because of the incidence of OPR with a positive lateral margin (16% vs 0% with ESD vs EMR). Histopathology (cancer), size (> or =20 mm) and macroscopic type (laterally spreading tumors) were shown to be significant risk factors for that incidence. For tumors with these factors, ESD showed a higher CR rate than did EMR. However, ESD required longer operating times and tended to have a higher rate of perforation compared with EMR. ESD was aborted halfway in seven cases due to technical difficulties and perforation. CONCLUSION: ESD and EMR have different characteristics as treatment for colorectal tumors. Careful evaluation of the lesion and of the balance between benefits and risks are mandatory before selecting either of these treatments for colorectal tumors.

Dural arteriovenous fistula presenting as an acute subdural hemorrhage that subsequently progressed to a chronic subdural hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: Non-traumatic subdural hemorrhage (SDH) caused by dural arteriovenous fistula (DAVF) is rare and is usually accompanied by intracerebral hemorrhage (ICH) and/or subarachnoid hemorrhage (SAH). This report describes a very rare case of DAVF that caused non-traumatic acute SDH without ICH or SAH, which subsequently progressed into chronic SDH. CASE REPORT: The patient presented with a sudden-onset severe headache, and was diagnosed with acute SDH by computed tomography. Cerebral angiography showed a DAVF on the left convexity adjacent to the superior sagittal sinus (SSS). This DAVF drained to the SSS and to the pterygoid venous plexus via the left middle fossa without retrograde flow (Type I according to the Cognard classification). The SDH was thickest at the lower convexity, which suggested that the draining vein of the DAVF was responsible for the bleeding. INTERVENTION: The SDH slowly progressed for two weeks. The DAVF was successfully treated with transarterial embolization using N-butyl 2-cyanoacrylate. The SDH was resolved via burr-hole drainage surgery. CONCLUSION: This is the first reported case of DAVF that caused non-traumatic progression to SDH. As DAVF can be the cause of acute and chronic SDH, cerebral angiography is recommended for non-traumatic acute SDH as well as for intractable chronic SDH.

Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients.

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice.

Two cases of a dural arteriovenous fistula mimicking a brain tumor.

SUMMARY: Dural arteriovenous fistula (d-AVF) is relatively rare. Some cases of atypical locations are often difficult to distinguish from other vascular disorders or tumors because those d-AVFs show various onsets, such as subcortical bleeding and venous infarctions. We encountered two cases of d-AVF with severe brain edema that took adequate time to distinguish from brain tumors. A 68-year-old man visited his local physician complaining of dizziness. He was diagnosed with a cerebral infarction due to the presence of an abnormal cerebellar signal on magnetic resonance imaging (MRI) and was treated by drip infusion. However, he did not recover and was admitted to our hospital with suspicion of a brain tumor. A 75-year-old woman with an onset of progressive dementia and gait disturbance showed severe edema of the right-front temporal lobe on MRI. Both these cases were examined by single photon emission computed tomography or positron emission tomography and were scheduled for craniotomy and biopsy based on the diagnosis of brain tumor. We performed preoperative angiography and found d-AVFs. We embolized the d-AVFs with liquid material and both patients recovered well. Brain edema from d-AVF or a tumor can be distinguished by carefully reading the MRI with findings such as the distribution of the edemas, differences on diffusion-weighted images, and contrast-enhanced images. Therefore, it is important to provide initial accurate diagnoses to prevent patient mistrust and irreversible disease conditions.

A successful treatment with carotid arterial stenting for symptomatic internal carotid artery severe stenosis with ipsilateral persistent primitive hypoglossal artery: case report and review of the literature.

A 68-year-old male presented with a syncopal attack subsequent to acute myocardial infarction. His ultrasonographic and radiological examination revealed severe left internal carotid artery (ICA) stenosis and the presence of a persistent primitive hypoglossal artery (PPHA) immediately distal to the stenosis. The bilateral anterior and left middle cerebral arteries, and the vertebrobasilar system were opacified via the stenotic ICA. Carotid arterial stenting was selected as the treatment method because the lesion was high and a shunt placement during carotid endarterectomy was considered to be technically difficult. A self-expanding stent was successfully deployed with flow control, and the patient was discharged six days after surgery without any neurological deficit. There are sixteen reported cases including ours of PPHA associated with ICA stenosis presenting with ischemic attacks of the vertebrobasilar system. To the best of our knowledge, the current case is the first report of a cervical ICA stenosis with ipsilateral carotid-basilar anastomosis treated with carotid arterial stenting.

Fine mapping and DNA fiber FISH analysis locates the tobamovirus resistance gene L3 of Capsicum chinense in a 400-kb region of R-like genes cluster embedded in highly repetitive sequences.

The tobamovirus resistance gene L(3) of Capsicum chinense was mapped using an intra-specific F2 population (2,016 individuals) of Capsicum annuum cultivars, into one of which had been introduced the C. chinense L(3) gene, and an inter-specific F2 population (3,391 individuals) between C. chinense and Capsicum frutescence. Analysis of a BAC library with an AFLP marker closely linked to L(3)-resistance revealed the presence of homologs of the tomato disease resistance gene I2. Partial or full-length coding sequences were cloned by degenerate PCR from 35 different pepper I2 homologs and 17 genetic markers were generated in the inter-specific combination. The L(3) gene was mapped between I2 homolog marker IH1-04 and BAC-end marker 189D23M, and located within a region encompassing two different BAC contigs consisting of four and one clones, respectively. DNA fiber FISH analysis revealed that these two contigs are separated from each other by about 30 kb. DNA fiber FISH results and Southern blotting of the BAC clones suggested that the L(3) locus-containing region is rich in highly repetitive sequences. Southern blot analysis indicated that the two BAC contigs contain more than ten copies of the I2 homologs. In contrast to the inter-specific F2 population, no recombinant progeny were identified to have a crossover point within two BAC contigs consisting of seven and two clones in the intra-specific F2 population. Moreover, distribution of the crossover points differed between the two populations, suggesting linkage disequilibrium in the region containing the L locus.

Side selection of pterional approach for anterior communicating artery aneurysms--surgical anatomy and strategy.

BACKGROUND: To evaluate our decision policy based on vertical aneurysm projection for selecting the side of the pterional approach for the surgical treatment of anterior communicating artery aneurysms. METHODS: Inferiorly projecting aneurysms were treated through the dominant A1 side, and superiorly projecting aneurysms were treated through the side of aneurysm fundus projection. We analysed postoperative outcome and surgical complications, and the correlations between the anatomical factors such as position (high or low), projection (dorsal or anterior), and the plane containing both A2 vessels (open A2 plane defined as the A2 of the approach side located more posteriorly than the contralateral A2; closed A2 plane as the ipsilateral A2 located more anteriorly than the contralateral A2), to assess the surgical requirements of approaches in patients with superiorly projecting aneurysms. FINDINGS: A favorable outcome was achieved in 95.1% of patients with inferior type aneurysms and 85.2% of patients with superior type aneurysms (P = 0.088). Surgical complications occurred in 8.9% of patients with inferior type aneurysms and 17.9% with superior type aneurysms. However, there was a distinct group of patients with superior type aneurysms characterised by a closed A2 plane, in which the ipsilateral A2 was located anterior to the contralateral A2, in whom the approach toward the neck was significantly more difficult, requiring A2 displacement or gyrus aspiration, and resulting in a neck remnant and more surgical complications such as vascular injury or cerebral contusion. This group also had a significantly high correlation with high position and dorsal projection of aneurysms causing more difficult dissection. CONCLUSIONS: This policy provided good postoperative outcomes. However, use of skull base techniques or the interhemispheric approach, instead of the normal pterional approach, may further improve the postoperative outcome for closed A2 plane aneurysms.

Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer.

BACKGROUND: We recently established a novel assay for specific activity (SA) of cyclin-dependent kinases (CDKs) using small tumor samples (>/=8 mm(3)). The aim of this study was to investigate the prognostic significance of CDK1SA and CDK2SA in human breast cancer. METHODS: CDK1SA and CDK2SA were determined in 284 breast cancer patients and their prognostic significance was investigated. RESULTS: Tumors with high CDK1SA and high CDK2SA showed significantly poorer 5-year relapse-free survival than those with low CDK1SA and low CDK2SA, respectively (66.9% vs 84.2% for CDK1SA; 43.6% vs 83.6% for CDK2SA). Moreover, combined analysis of CDK1SA and CDK2SA enabled the classification of breast tumors into high-risk and low-risk groups, where tumors in the high-risk group were strongly associated with unfavorable prognosis (5-year relapse-free survival 69.4% for the high-risk group and 91.5% for the low-risk group). Multivariate analysis showed that the risk determined by combined analysis of CDK1SA and CDK2SA is a significant (hazard ratio 3.09, P < 0.001) prognostic indicator for relapse, especially in node-negative patients (hazard ratio 6.73, P < 0.001). CONCLUSION: Determination of CDK1SA and CDK2SA may be useful in the prediction of outcomes in breast cancer patients and has potential for use as a routine laboratory test.

Nodular-type muscle sarcoidosis developing after a dog bite.

We report a 46-year-old woman who experienced swelling of the right thigh around the wound caused by a dog bite. Physical findings, laboratory findings, imaging studies, and muscle biopsy showed that this was nodular-type muscle sarcoidosis. This is an unusual case of sarcoidosis, and the possibility is discussed that a dog bite may serve as a trauma to trigger sarcoidosis in genetically predisposed individuals.