Evaluating anthropogenic and environmental tritium effects using precipitation and Hokkaido snowpack at selected coastal locations in Asia.

Tritium dating requires a good understanding of the tritium and water inputs into hydrologic systems, including their main trends due to latitudinal, seasonal and altitudinal effects. Although tritium reached ambient levels at the end of the 20th century, tritium released from nuclear facilities and bomb tests since then has the potential to confound use of tritium for age dating. We therefore collected precipitation and snowpack samples for tritium analysis to confirm that tritium levels in Japanese precipitation had not exceeded ambient levels following the North Korean nuclear tests in January 6th 2016 and September 3rd 2017. As the result, the highest tritium concentration was 5.52(±0.27)TU at samples collected from January 8 to 11th at one Honshu and four Hokkaido locations and samples collected at six Honshu locations had 8.01(±1.5)TU from September 6 to 19th 2017. Confirming ambient tritium concentrations after both events we investigated the latitude tritium effect at selected coastal stations in Asia, indicating a break of latitude trend around Tokyo area, and established the latitude scaling factors to the north and south of the Tokyo area data. The seasonal trend was investigated during the winter-spring 2016 in precipitation samples confirming the higher spring tritium compared with winter continental tritium values. The altitude effect on tritium and stable (18O and 2H) isotopes was observed in Hokkaido snowpack, which had tritium concentrations ranging between 4.08 and 5.93 TU during March-April, and demonstrated two trends for western and central Hokkaido mountain ranges. Using established latitude and altitude scaling factors with the long-term continuous time-series of monthly Tokyo area tritium we estimated the annual weighted tritium at 110 meteorological stations in Japan with monthly precipitation demonstrating the applicability of this approach for future tritium-tracer studies across Asia.

Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones.

Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18ß-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling enhances synchronised activities among neighbouring KNDy neurones, and that both neurone-neurone and neurone-glia communications via gap junctions possibly contribute to synchronised activities among KNDy neurones.

A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia.

PURPOSE: Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC). METHODS: Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45mg to 30mg. The primary endpoint was objective response rate at 16weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R). RESULTS: 74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58years [31-87]. In PL-S group, 10 (26%) partial responses (PR) and 20 (51%) stable disease (SD) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities observed at the 30 mg starting dose were hypertension (27%), fatigue (20%) and diarrhea (14%). The median progression-free survival for all patients was 4.9months [3.9-7.0], 7.2months [4.3-9] for PL-S and 3.7months [2.6-4.5] for PL-R groups. The median overall survival was 18.9months (95% CI: 13.5-31.5); 27.7months [17.8-43.3] for PL-S and 11.9months [8.1-18.9] for PL-R groups. CONCLUSION: Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30mg od.

A new disorder of praxis in neurodegenerative disease that may be part of Alzheimer's disease.

Apraxia is a well-known disorder of praxis and is caused mainly by damage to the left parietal lobe. We presented two cases of neurodegenerative disease with a distinct disorder of praxis, predominantly involving left parietal lobe. While both patients could understand what they should do, they were not able to initiate action and often stopped during execution of actions. They had no apraxia and no temporal and spatial errors on praxis. Magnetic resonance imaging of both patients showed atrophy of the left parieto-occipital and temporo-occipital lobes, and single photon emission computed tomography showed hypoperfusion in the same lobes. Moreover, one of our cases, using [11C] PIB PET, demonstrated increased uptake in the cerebral cortices, suggesting Alzheimer's disease. The symptoms described are different from other disorders of praxis and similar to bradyphrenia or freezing.

[Intraoperative direct angiography for the diminutive central pulmonary artery in a patient with major aortopulmonary collateral arteries].

It can be difficult to judge the degree of arborization of diminutive central pulmonary arteries (cPA) in patients with major aortopulmonary collateral arteries (MAPCA). Even through preoperative cardiac catheterization may not give adequate information. We introduce intra-operative direct angiography of diminutive cPA for patients with MAPCA. This would be one of the good options to judge the degree of arborization of the diminutive cPA, and to decide an initial surgical treatment. In this case, unifocalization of MAPCA without patch augmentation of pulmonary arteries, and an aortopulmonary shunt were performed at the 1st procedure. As enough growth of the cPA was obtained, this patient did not require additional patch augmentation of the pulmonary artery at the time of complete repair.

Brodmann area 12: an historical puzzle relevant to FTLD.

BACKGROUND: Brodmann brain maps, assembled in 1909, are still in use, but understanding of their animal-human homology is uncertain. Furthermore, in 1909, Brodmann did not identify human area 12 (BA12), a location now important to understanding of frontotemporal lobar degeneration (FTLD). METHODS: We re-examined Brodmann's areas, both animal and human, in his 1909 monograph and other literature, both historical and contemporary, and projected BA12 onto the medial surface of a fixed human brain to show its location. RESULTS: We found Brodmann did identify human BA12 in later maps (1910 and 1914), but that his brain areas, contrary to his own aims as a comparative anatomist, are now used as physiologic loci in human brain. CONCLUSION: Because of its current link with frontotemporal dementia, BA12's transition from animal (1909) to human (1910 and 1914) is not only an historical puzzle. It impacts how Brodmann's areas, based on comparative animal-human cytoarchitecture, are widely used in current research as functional loci in human brain.

Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

BACKGROUND: Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. METHODS: Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. RESULTS: A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) CONCLUSIONS: Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.

Intra- and extracranial solitary fibrous tumor of the trigeminal nerve: CT and MR imaging appearance.

We describe a rare case of SFT existing along the mandibular division of the trigeminal nerve and extending down into the infratemporal fossa through the foramen ovale. The tumor showed heterogeneous hypointensity on T2-weighted images and marked enhancement on CT and MR images.

Clinical significance of topical instillation technique in Japanese glaucoma patients.

The clinical significance of a proper eye drop application technique was evaluated in Japanese glaucoma patients. Patients diagnosed with primary open-angle glaucoma having intraocular pressure (IOP) greater than 21 mmHg were treated with eye drops at home. In some patients, however, the topical treatment was ineffective. They returned to the hospital to receive surgical treatment. On admission, 56% of these patients had IOP greater than 21 mmHg. Patient instillation technique was evaluated based on the proximity of the eyedropper tip to the eyes, application position, eyelid closure, treatment (removal) of excess fluid, and nasolacrimal occlusion. In addition, pharmacists interviewed patients to determine the level of understanding of glaucoma, knowledge of prescribed drugs, home application technique, and sensation after application. Multivariate analysis revealed that the key factors influencing the control of IOP to less than 21 mmHg with topical medication were: application of drops in the center of the eye and removal of excessive fluid, in addition to gender and age. Proper topical application at home was dependent on the patient's understanding of the disease, knowledge of prescribed drugs, patient education on the use of drugs, the competence of the instructor, and knowledge of correct application technique. This study indicates that easily comprehensible patient education on the use of eye drops, the nature of glaucoma and the proper use of prescribed drugs is vital to improving the clinical efficacy of topical ophthalmic medication of glaucoma in adult patients.

Is adjuvant therapy necessary for stage IA and IB uterine papillary serous carcinoma and clear cell carcinoma after surgical staging?

Adjuvant therapy of early-stage uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) is controversial. We conducted a prospective cohort study to evaluate outcomes of patients with early-stage UPSC or CCC who were followed without adjuvant therapy after complete surgical staging. From 2000 to 2006, we evaluated all consecutive patients with stage IA/IB UPSC or CCC who had surgical staging by a gynecological oncologist at the London Health Sciences Centre, Canada. Follow-up consisted of history and physical examination every 3 months for 2 years, then every 6 months for the next 3 years. Primary outcome measure was 2-year disease-free survival. There were 22 evaluable patients. Mean patient age was 63.4 years. Median number of pelvic and para-aortic lymph nodes resected was 15 (range 2-39) and 4 (range 0-12), respectively. Thirteen had UPSC, seven had CCC, and two had both UPSC and CCC. Nine had stage IA and 13 had stage IB disease. Median follow-up was 25 months (range 6-72). Only one patient has recurred (stage IB UPSC, isolated vault recurrence 10 months after surgery), but she is well 9 months after receiving pelvic radiotherapy and vault brachytherapy. Two-year disease-free survival was 95%. These results suggest that adjuvant therapy may not be necessary for stage IA and IB UPSC and CCC after surgical staging. Further prospective evaluation of different adjuvant therapy practices is required for early-stage UPSC and CCC, which may be useful in the design of future clinical trials.

Very close relationship of the chloroplast genomes among Saccharum species.

We recently determined the complete sequence of the sugarcane chloroplast genome. Here, we have used the information for a comprehensive phylogenetic analysis of the genus Saccharum, using all six species (13 accessions). The polymorphisms between sugarcane and maize in 26 chloroplast genome regions were used for the analysis. In 18 of the 26 regions (a total of 5,381 bp), we found 41 mutations involving 17 substitutions, three inversions, six insertion/deletion mutations, and 15 simple sequence repeat length polymorphisms. Based on these results, we calculated a phylogenetic tree of the genus Saccharum, in which all six species are clearly separated. By the analysis, (1) S. sinense and S. barberi, which have identical sequences, belong to the same clade, whereas the other four species, S. officinarum, S. robustum, S. edule, and S. spontaneum, form an independent clade; (2) S. spontaneum has a paraphyletic relationship with the other five species; and (3) no or very low intraspecific variation was observed in S. officinarum, S. robustum, S. sinense, S. barberi, and S. edule, whereas higher intraspecific variation was observed in S. spontaneum. Based on the number of nucleotide substitutions, the divergence time between S. officinarum and S. spontaneum, and between S. officinarum and maize were calculated to be about 730-780 thousand years ago and about 5.9 million years ago, respectively. These results suggest that the cytoplasm of Saccharum species are very closely related.

Inhibitory effect of green tea catechins on cysteine proteinases in Porphyromonas gingivalis.

The purpose of this study was to examine the effects of catechins and their derivatives on the activities of Arg-gingipain (Rgp) and Lys-gingipain (Kgp) in Porphyromonas gingivalis. Catechin derivatives, which included (-)-epigallocatechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-catechin gallate, significantly inhibited the Rgp activity. The 50% inhibitory concentrations (IC50s) of these catechin derivatives for Rgp ranged from 3 to 5 microm. While (-)-epigallocatechin and (-)-gallocatechin moderately inhibited Rgp activity (IC50s, 20 microm), (-) -epicatechin, (+)-catechin, and gallic acid were not effective, with IC50s greater than 300 microm. Further, some of the catechin derivatives tested also inhibited the Kgp activity, though to a lesser extent than inhibition of the Rgp activity. These findings suggest that green tea catechins may have the potential to reduce periodontal breakdown resulting from the potent proteinase activity of P. gingivalis.

Inhibitory effects of green tea catechins on protein tyrosine phosphatase in Prevotella intermedia.

Members of the Prevotella intermedia group possess protein tyrosine phosphatase (PTPase). The purpose of this study was to investigate the effects of catechin derivatives from Japanese green tea on the activity of PTPase in P. intermedia and related organisms. Multilocus enzyme electrophoresis of alkaline phosphatase derived from P. intermedia, Prevotella nigrescens, Prevotella pallens and Porphyromonas gingivalis revealed a species-specific migration pattern. Among the tea catechin derivatives tested, (-)-epigallocatechin gallate (EGCg), similar to orthovanadate, a specific inhibitor for PTPase, was effective in inhibiting the PTPase activity in P. intermedia at 0.5 microm, and related species at 5 microm. The results suggested that the inhibitory effect observed is due to the presence of galloyl moiety in the structure. In contrast, neither the green tea catechins nor orthovanadate inhibited the phosphatase activity in P. gingivalis, suggesting that this organism possessed a different family of alkaline phosphatase.

Important role of junctophilin in nematode motor function.

Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are shared by excitable cells and seem to be the structural ground for cross-talk between cell-surface and intracellular ionic channels. Our current studies have identified junctophilins (JPs) as members of a novel transmembrane protein family in the junctional membrane complex. Biochemical and gene-knockout studies have suggested that JPs contribute to the formation of the junctional membrane complex by spanning the intracellular store membrane and interacting with the plasma membrane. We report here invertebrate JPs in fruit fly and nematode. Three distinct JP subtype genes are found in the mammalian genome, while a single JP gene exists in either invertebrate genome. Mammalian and invertebrate JPs share characteristic structural features, although some intervening sequences are found in invertebrate JPs. A reporter assay indicated that the JP gene is predominantly activated in muscle cells in nematode. Nematodes, in which expression of JP was inhibited by RNA-mediated interference (RNAi), showed hypolocomotion. Taking account of the cell-type-specific expression and data from previous reports, the hypolocomotion is likely to be due to the deficiency of junctional membrane structures and the resulting reduction of Ca(2+) signaling during excitation-contraction coupling in muscle cells.

Purification, characterization, and cDNA cloning of a novel soluble saxitoxin and tetrodotoxin binding protein from plasma of the puffer fish, Fugu pardalis.

Some species of puffer fish have been reported to possess both of tetrodotoxin and saxitoxin, which share one binding site on sodium channels. We purified a novel soluble glycoprotein that binds to these toxins from plasma of the puffer fish, Fugu pardalis, and named puffer fish saxitoxin and tetrodotoxin binding protein (PSTBP). PSTBP possessed a binding capacity of 10.6 +/- 0.97 nmol x mg(-1) protein and a K(d) of 14.6 +/- 0.33 nm for [(3)H]saxitoxin in equilibrium binding assays. [(3)H]Saxitoxin (10 nm) binding to PSTBPs was half-inhibited by the presence of tetrodotoxin and saxitoxin at 12 microm and 8.5 nm, respectively. From the results of gel filtration chromatography (200 kDa) and SDS/PAGE (104 kDa), PSTBP was suggested to consist of noncovalently linked dimers of a single subunit. PSTBP was completely deglycosylated by glycopeptidase F, producing a single band at 42 kDa. Two highly homologous cDNAs to each other coding PSTBP (PSTBP1 and PSTBP2, the predicted amino-acid identity 93%), were obtained from a cDNA library of F. pardalis liver. These proteins consisted to two tandemly repeated homologous domains. The predicted amino-acid sequences of PSTBP1 and 2 were not homologous to that of saxiphilin, a reported saxitoxin binding protein, or sodium channels, but their N-terminus sequences were homologous to that of the reported tetrodotoxin binding protein from plasma of Fugu niphobles, which has not been fully characterized. The partially homologous cDNA sequences to PSTBP1 and 2 were also found in expressed sequence tag clones of nontoxic flounders liver. Presumably, PSTBP is involved in accumulation and/or excretion of toxins in puffer fish.

Effects of lidocaine on basilar membrane vibration in the guinea pig.

The effects of lidocaine on basilar membrane (BM) vibration and compound action potential (CAP) were studied in guinea pigs in order to elucidate the site of lidocaine action in the cochlea. BM vibration was measured with a laser Doppler vibrometer through an opening made in the lateral bony wall of the scala tympani at the basal turn. Ten min after local administration of lidocaine (250 microg) into the scala tympani, the velocity of BM vibration and the CAP amplitude decreased significantly at around the characteristic frequency of the stimulus sound (p < 0.05). The maximum decreases were 4 dB in the velocity of the BM vibration and 40 dB in the CAP amplitude. In contrast, such changes were not observed after i.v. injection of lidocaine (1.5 mg/kg). These results suggest that when lidocaine is administered locally in the cochlea it acts not only on the cochlear nerve but also on the outer hair cells.

Hysteroscopic endomyometrial resection of three uterine sarcomas.

STUDY OBJECTIVE: To describe our experience with three uterine sarcomas associated with hysteroscopic endometrial ablation. DESIGN: Cohort study (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospitals. PATIENTS: Three of 2402 women undergoing hysteroscopic endometrial ablation who had uterine sarcomas. INTERVENTION: Hysteroscopic endomyometrial resection. MEASUREMENTS AND MAIN RESULTS: One low-grade endometrial stromal sarcoma and two carcinosarcomas were resected. After hysterectomy in two patients, no residual cancer was identified in one of them. The third patient was an 82-year-old woman with moderate menorrhagia who refused hysterectomy. After endomyometrial resection she remained amenorrheic for the last 14 months of her life. CONCLUSION: From our experience the incidence of uterine sarcomas is approximately 1/800 women undergoing hysteroscopic ablation for abnormal uterine bleeding. Complete endomyometrial resection is feasible and may be offered as diagnostic and palliative therapy in women at high risk for hysterectomy.

Diamagnetic activity above Tc as a precursor to superconductivity in La2-xSrxCuO4 thin films.

Superconductors show zero resistance to electric current, and expel magnetic flux (the Meissner effect) below the transition temperature (Tc). In conventional superconductors, the 'Cooper pairs' of electrons that are responsible for superconductivity form only below Tc. In the unconventional high-Tc superconductors, however, a strong electron correlation is essential for pair formation: there is evidence that some pairs are formed above Tc in samples that have less than the optimal density of charge carriers (underdoped) and an energy gap-the 'pseudogap'-appears to be present. Moreover, excitations that look like the vortices that carry magnetic flux inside the superconducting state have been reported above Tc (refs 6, 7). Although the origin of the pseudogap remains controversial, phase fluctuations above Tc, leading to some form of local superconductivity or local pairing, seem essential. Here we report magnetic imaging (scanning SQUID microscopy) of La2-xSrxCuO4 thin films. Clear quantized vortex patterns are visible below Tc (18-19 K), and we observe inhomogeneous magnetic domains that persist up to 80 K. We interpret the data as suggesting the existence of diamagnetic regions that are precursors to the Meissner state.