Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases.

PURPOSE: The objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Seventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0. RESULTS: The median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47-62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06-3.01; P=0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77-15.27; P<0.001) tumour volume (>12cc vs. ≤12cc; HR, 1.84; 95% CI, 1.10-3.11; P=0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19-0.70; P=0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients. CONCLUSION: With acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.

Distribution of ASIC4 transcripts in the adult wild-type mouse brain.

Acid-sensing ion channel 4 (ASIC4) belongs to the ASIC gene family of neuronal proton-gated cation channels, and is the least understood subtype among the members. Previous studies of ASIC4 expression in the mammalian central nervous system have shown that ASIC4 is abundantly expressed in the spinal cord and in various brain regions, such as the cerebral cortex, the hippocampus, and the cerebellum. However, the detailed distribution of ASIC4 transcripts in mammalian brains still remains to be elucidated. In the present study, radioactive in situ hybridization histochemistry with an ASIC4-specific cRNA probe was performed on wild-type mouse brains, followed by X-gal staining experiments with Asic4-lacZ reporter mice Asic4tm1a(KOMP)Mbp. It was found that ASIC4 mRNAs were widely expressed throughout the wild-type brain, but preferentially concentrated in the olfactory bulb, the piriform cortex, the caudate putamen, the preoptic area, the paraventricular nucleus, the medial habenular nucleus, the pretectal area, the lateral geniculate nucleus, the amygdaloid complex, the superior colliculus, the interpeduncular nucleus, and the granule cell layer of the ventral hippocampus, and these results were in agreement with the X-gal-positive reactions observed in the mutant brain. In addition, X-gal staining combined with immunohistochemistry identified intense signals for ASIC4 transcriptional activity in most of the choline acetyltransferase (ChAT)-positive principal neurons located in the basal forebrain cholinergic nuclei. Our data provide useful information to speculate possible roles of ASIC4 in diverse brain functions.

Neuropathic Pain Features in Patients with Bone Metastases.

AIMS: The results of previous randomised controlled trials suggest that radiation oncologists should consider the presence of neuropathic pain when they prescribe dose fractionations for painful bone metastases. Although validated screening tools for neuropathic pain features are currently available, the prevalence of such features among patients with painful bone metastases is still poorly understood. The purpose of this study was to estimate the prevalence of neuropathic pain features among patients who received palliative radiotherapy for painful bone metastases. MATERIALS AND METHODS: We conducted a cohort survey of consecutive patients who received palliative radiotherapy for painful bone metastases at St Luke's International Hospital between 2013 and 2014. Patients were prospectively assessed before radiotherapy using the validated screening questionnaire to identify neuropathic pain components in Japanese patients. Pain with neuropathic features was prospectively defined using the total score of the seven-item questionnaire and a cut-off score ≥9. The pain response was assessed 2 months after the start of radiotherapy according to the criteria defined by the International Bone Metastases Consensus Working Party. RESULTS: Eighty-seven patients were assessed. Twenty-four per cent of patients (95% confidence interval: 16-35%) were diagnosed as having pain with neuropathic features. On multivariate analysis, no significant correlations were seen between neuropathic pain features and patient characteristics. Sixty-four patients (74%) were assessable 2 months after the start of radiotherapy. Overall response rates were 59% (95% confidence interval: 33-82%) in patients with neuropathic features and 55% (95% confidence interval: 40-70%) in those without such features. CONCLUSIONS: A considerable proportion of the patients were proven to have bone pain with neuropathic features. Further investigations are warranted to validate symptom assessment tools in cooperation with pain distribution and image findings, and to clarify if the presence of neuropathic pain affects the response to palliative radiotherapy.

PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells.

We analyzed a complex chromosomal translocation in a case of embryonal rhabdomyosarcoma (RMS) and showed that it generates the fusion gene PAX3 (paired box 3)-NCOA2 (nuclear receptor coactivator 2). To understand the role of this translocation in RMS tumorigenesis, we established two types of stable mouse myoblast C2C12 cell lines expressing PAX3-NCOA2 and PAX3-FOXO1A (forkhead box O1A), respectively. Compared with control cells, PAX3-NCOA2 cells grew faster, were more motile, were less anchorage dependent, progressed more quickly through the G1/S phase of cell cycle and showed greater transcriptional activation of the PAX3 consensus-binding site. However, PAX3-NCOA2 cells proliferated more slowly and differentiated more weakly than did PAX3-FOXO1A cells. Both PAX3-NCOA2 cells and PAX3-FOXO1A cells formed tumors in nude mice, although the PAX3-NCOA2-induced tumors grew more slowly. Our results may explain why NCOA2 rearrangement is mainly found in embryonal rhabdomyosarcoma, which has a better prognosis than alveolar rhabdomyosarcoma, which expresses the PAX3-FOXO1A fusion gene. These results indicate that the PAX3-NCOA2 fusion gene has a dual role in the tumorigenesis of RMS: promotion of the proliferation and inhibition of the myogenic differentiation of RMS cells.

Monitoring of methylergometrine in human breast milk by solid-phase extraction and high-performance liquid chromatography with fluorimetric detection.

A high-performance liquid chromatographic assay has been developed for the detection and quantification of the conventional postnatal uterotonic drug, methylergometrine, in human breast milk using a C-18 reversed-phase column by isocratic elution. The analytical method consisted of sample clean-up by solid-phase extraction, and the fluorescence detection required only 8.5 min per sample for separation and quantitation. This assay gave intra- and inter-assay coefficients of variation of less than 7.9% and 7.7%, respectively, and the detection limit was approximately 50 pg/ml. This method was applied for drug level monitoring in the breast milk of patients given methylergometrine.

[Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade; report of a case].

We report a case of successful treatment of a ruptured distal aortic arch aneurysm with cardiac tamponade by using selective cerebral perfusion for protecting the brain. A 79-year-old man had sudden onset of severe chest and back pain. Chest computed tomography (CT) suggested an acute aortic dissection. He was immediately transferred to the emergency room of our hospital. Echocardiography performed on admission revealed intrapericardial fluid, and hemodynamic monitoring suggested cardiac tamponade. After pericardiocentesis and removal of 400 ml bloody fluid, his hemodynamic condition became stable. Enhanced chest CT showed ruptured distal aortic arch aneurysm with pericardial and pleural effusion. Emergency patch plasty of the aneurysm under extracorporeal circulation (ECC) was performed, assisted by selective cerebral perfusion and deep hypothermia. The patient's postoperative course was uneventful, except for minor transient respiratory troubles, and he was able return to his usual activity.

Semiaphis dauci (Fabricius) (Insecta, Hemiptera, Aphididae) ­ formal record of occurrence on arracacha (Arracacia xanthorrhiza Bancr) (Apiaceae) in Brazil, morphological characterization, description of damages and arthropods associated to the culture / Semiaphis dauci (Fabricius) (Insecta, Hemiptera, Aphididae) ­ registro formal de ocorrência em mandioquinha­salsa (Arracacia xanthorrhiza Bancr) (Apiaceae) no Brasil, caracterização morfológica, descrição dos danos e artrópodes relacionados à cultura

This paper reports formally the occurrence and describes the damages by Semiaphis dauci (Fabricius, 1775) (Insecta, Hemiptera, Aphididae, Aphidinae, Macrosiphini) on arracacha (Arracaciaxanthorrhiza Bancr.) (Apiaceae) in Brazil. The infestation was initially noted on April/2002 at Núcleo de Produção de Mudas, Departamento de Sementes Mudas e Matrizes, Coordenadoria de Assistência Técnica Integral, Secretaria de Agricultura e Abastecimento, São Bento do Sapucaí, State of São Paulo. Posteriorly the occurrence was detected in other parts of the municipality of São Bento do Sapucaí such as Serrano, Paiol Grande and Cantagalo, being the incidence higher in localities at lower altitudes. The colonies, with large number of individuals, were settled on both sides of the leaves and also hidden under petiole, but with lower number of specimens. The adult plants were underdeveloped and the growing of aphid colonies induced the blossoming. In the seedlings the symptoms were severer with reduction in the development and death of plants. When the colonies were placed in the dorsal side of the leaves, there was a tendency to wrinkling and rolling to upper side that was used as shelter by the aphids. Morphological characterization, illustrations and notes on biology of S. dauci and a survey of the Arthropoda related with A. xanthorrhiza are also presented.

Este trabalho efetua o registro formal de ocorrência e descreve os danos de Semiaphis dauci (Fabricius, 1775) (Insecta, Hemiptera, Aphididae, Aphidinae, Macrosiphini) em cultura de mandioquinha-salsa (Arracacia xanthorrhiza Bancr.) (Apiaceae) no Brasil. A infestação foi observada, inicialmente, em abril/2002, no Núcleo de Produção de Mudas, Departamento de Sementes Mudas e Matrizes, Coordenadoria de Assistência Técnica Integral, Secretaria de Agricultura e Abastecimento, São Bento do Sapucaí, SP. Posteriormente, a ocorrência foi detectada em outras localidades do município como Serrano, Paiol Grande e Cantagalo sendo que a incidência foi maior nas áreas de menor altitude. As colônias estavam localizadas em ambas as faces das folhas, e em menor número no pecíolo escondidas na bainha da folha. As plantas adultas apresentavam subdesenvolvimento e o aumento das colônias induzia o florescimento. Nas mudas os sintomas foram mais severos com redução no desenvolvimento e posterior morte das plantas. Quando havia formação de colônias na superfície superior das folhas, havia tendência de encarquilhamento e enrolamento para cima, servindo de abrigo para os pulgões. Caracterização morfológica, ilustrações, notas sobre a biologia de S. dauci e levantamento dos Arthropoda relacionados com A. xanthorrhiza também são apresentados.

Two dimensional density and its fluctuation measurements by using phase imaging method in GAMMA 10.

Two dimensional (2D) plasma image analysis is useful to study the improvement of plasma confinement in magnetically confined fusion plasmas. We have constructed a 2D interferometer system with phase imaging method for studying 2D plasma density distribution and its fluctuation measurement in the tandem mirror GAMMA 10. 2D profiles of electron density and its fluctuation have been successfully obtained by using this 2D phase imaging system. We show that 2D plasma density and fluctuation profiles clearly depends on the axial confining potential formation with application of plug electron cyclotron heating in GAMMA 10.

Radial density profile measurement by using the multichannel microwave interferometer in GAMMA 10.

Plasma density radial profile measurements are an important study for fusion plasma researches. We reconstructed a multichannel microwave interferometer for radial plasma electron density and density fluctuation measurements with both changing the transmission horn position and using the Teflon lens by only using this system in a single plasma shot. By using this system, we can successfully measure the radial density and density fluctuation spectra in a single plasma shot.

Involvement of the protein kinase Cgamma isoform in development of tolerance to nitrous oxide-induced antinociception in mice.

Prolonged exposure to nitrous oxide (N2O) results in development of acute tolerance to its antinociceptive effect. Cross-tolerance to N2O-induced antinociception is also observed in morphine-tolerant animals. Despite increasing evidence of tolerance development to N2O-induced antinociception, the details of the mechanisms that underlie this tolerance remain unknown. The present study was conducted to investigate the involvement of brain protein kinase C (PKC) isoform in these two types of tolerance to N2O-induced antinociception in mice. Prolonged exposure (41 min in total, including 30 min pre-exposure and 11 min of antinociceptive testing) to 70% N2O produced a reduction in N2O-induced antinociception, indicating development of acute tolerance. The prolonged exposure to 70% N2O caused an activation of PKCgamma isoform in the brain, but not the PKCepsilon isoform. Pretreatment with a PKCgamma-antisense oligonucleotide but not the corresponding mismatch oligonucleotide (i.c.v.) prevented the development of acute tolerance to N2O-induced antinociception. Chronic morphine treatment (10 mg/kg, s.c., b.i.d. for 5 days) resulted in development of tolerance to morphine-induced antinociception and cross-tolerance to N2O-induced antinociception. The development of tolerance to morphine and cross-tolerance to N2O were both inhibited by pretreatment with PKC inhibitor, chelerythrine (1 nmol, i.c.v.). Morphine-tolerant mice showed an activation of PKC within the brain, which was suppressed by pretreatment with chelerythrine (1 nmol, i.c.v.). Thus, activation of brain PKC, in particular, the PKCgamma isoform, appears to play an important role in the development of both acute tolerance and cross-tolerance to N2O-induced antinociception in mice.

[Ventricular septal perforation due to weak blunt chest trauma; report of a case].

We report a 67-year-old female patient with ventricular septal perforation after weak blunt chest trauma. She tumbled down on a frozen street. Approximately 1 week later, the patient was aware of shortness of breath on exertion. On admission, holosystolic murmur was detected on chest wall and routine electrocardiogram examination showed ST-T change which suggested myocardial ischemia. Acute myocardial infarction and ventricular septal defect with left-to-right shunt was suspected. The echocardiography and cardiac catheterization revealed the muscular type ventricular septal perforation near the apex with large left-to-right shunt flow (82% shunt ratio). The congestive heart failure was controlled successfully by conservative medical treatment. Surgical repair was scheduled on the 28th day after initial chest trauma because of large left-to-right shunt. A hole of about a diameter of 2 cm with fibrous edge of the muscular septum was closed through a left ventriculotomy using a Dacron patch under cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged without symptoms of congestive heart failure.

Observation and control of transverse energy-transport barrier due to the formation of an energetic-electron layer with sheared ExB flow.

Off-axis electron-cyclotron heating in an axisymmetric barrier mirror produces a cylindrical layer with energetic electrons, which flow through the central cell and into the end region. The layer, producing a localized bumped ambipolar potential Phi(C), forms a strong shear of radial electric fields E(r) and peaked vorticity with the direction reversal of E(r)xB sheared flow near the Phi(C) peak. Intermittent vortexlike turbulent structures near the layer are suppressed in the central cell by this actively produced transverse energy-transport barrier; this results in T(e) and T(i) rises surrounded by the layer.

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

Prototype of simulation of orthognathic surgery using a virtual reality haptic device.

A maxillofacial simulator can support education and training. In the present study, cutting, separation, and quantitative rearrangement of bone during orthognathic surgery were simulated by means of a haptic device with virtual tactile perception. Computed tomographic (CT) images of two patients with severe jaw deformity, one women and one man, were input into the device. In the woman, Le Fort I osteotomy of the maxilla and sagittal splitting ramus osteotomy of the mandible were initially simulated. During surgery with the haptic device, separation and rearrangement of the maxilla and the ramus of the mandible were initially processed. However, there was discrepancy and overlapping of the ramus with the mandible. Intraoral vertical osteotomy of the right ramus was then performed, with satisfactory results and less discrepancy and interference. The simulation was referred to at surgery, and satisfactory surgical assistance was postoperatively confirmed on CT images. The male patient had severe jaw deformity due to unequal growth between the ramuses, resulting in anterior crossbite. Sagittal splitting ramus osteotomy with rotation of the mandible was successfully simulated. Because of its versatility and functions, the present device was found to be useful for simulating various procedures for orthognathic surgery and thereby three-dimensionally determine surgical movements.

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Absence of somatic hypermutation of immunoglobulin heavy chain variable region genes in precursor B-lymphoblastic lymphoma: a study of four cases in childhood and adolescence.

Somatic mutation (SM) analysis provides a useful tool for understanding the suitable stage of differentiation of normal and neoplastic B cells. B-cell precursor neoplasms are considered to be somatically premutational. However, no reports have been made on the sequence analysis of SM in rearranged immunoglobulin heavy chain variable region (VH) genes in precursor B-lymphoblastic lymphoma (PB-LBL); as for B-cell acute lymphoblastic leukemia (B-ALL), the variable frequency of SM of the VH genes has been described. To better distinguish PB-LBL from B-ALL based on the stage at which differentiation occurs, we analyzed the SM of the VH genes in 4 children and adolescents with PB-LBL. In all 4 cases, there was no SM in complementarity-determining regions 1, 2, and 3 and in framework regions 2 and 3 of the VH genes, except for 1 mutation in 1 of 2 polymerase chain reaction products from 1 patient. Our data showed the absence of SM of lymphoma cells in PB-LBL, in addition to the developmentally regulated rearrangement of VH genes at the stage of B-cell precursor cells. The lack of mutation in VH gene sequences suggests that SM may differ between PB-LBL and B-ALL.

High-performance liquid chromatographic-fluorimetric assay of chymotrypsin-like esterase activity.

A sensitive and reproducible assay for the determination of chymotrypsin-like esterase activity is reported. This method is based on fluorimetric detection of a dansylated amino acid, 5-dimethylaminonaphthalene-1-sulfonyl-L-phenylalanine, enzymatically formed from the substrate 5-dimethylaminonaphthalene-1-sulfonyl-L-phenylalanine ethyl ester, after separation by high-performance liquid chromatography using a C18 reversed-phase column and isocratic elution. This method is sensitive enough to measure 5-dimethylaminonaphthalene-1-sulfonyl-L-phenylalanine at concentrations as low as 40 pmol/ml, yields highly reproducible results and requires less than 9.5 min per sample for quantitation. The optimum pH for chymotrypsin-like esterase activity was 7.7-8.3. The Km and Vmax values were, respectively 25 microM and 0.241 pmol/microg protein/h with the use of enzyme extract obtained from mouse kidney. The approximate molecular mass of this enzyme was estimated to be 67000 by gel filtration. Chymotrypsin-like esterase activity was strongly inhibited by N-tosyl-L-phenylalaline chloromethyl ketone. Among the mouse organs examined, the highest specific activity of the enzyme was found in lung. This new method would be useful for clarification of the physiological role of this enzyme.

Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori.

BACKGROUND: Human beta-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces. Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma. AIMS: To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa. SUBJECTS: Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used. H pylori was determined by the presence of urease activity and microscopic examination. METHODS: The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10(-9), 10(-8), 10(-7), 10(-6), or 10(-5) M of hBD-2 peptide. RESULTS: All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR. Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens. In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased. In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens. Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10(-5) M hBD-2 completely inhibited the proliferation of H pylori. CONCLUSIONS: H pylori infection induces hBD-2 expression in the human gastric epithelium. hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis.