Visualization of Nigrosome 1 from the Viewpoint of Anatomic Structure.

BACKGROUND AND PURPOSE: Parkinson disease is related to neurodegeneration and iron deposition in the substantia nigra pars compacta and nigrosome 1. However, visualization of nigrosome 1 via MR imaging is poor owing to the bilateral asymmetry, regardless of whether it is healthy. We focused on the magic angle and susceptibility effect and evaluated the anatomic slant structure of nigrosome 1 by tilting subjects' heads in the B0 direction. MATERIALS AND METHODS: To investigate the effectiveness of the magic angle, we tilted the volunteers' heads to the right and left in the B0 direction or not at all for evaluating correlations between the degree of head tilting and visualization of the right nigrosome 1 and left nigrosome 1 using 3D spoiled gradient-echo sequences with multiecho acquisitions. We evaluated the susceptibility of nigrosome 1 and the local field using quantitative susceptibility mapping to assess static magnetic field inhomogeneity. RESULTS: The heads tilted to the right and left showed significantly higher contrasts of nigrosome 1 and the substantia nigra pars compacta than the nontilted heads. No significant differences were observed in the visualization and susceptibility between the right nigrosome 1 and left nigrosome 1 for each head tilt. The effect of the magic angle was remarkable in the nontilted heads. This finding was supported by quantitative susceptibility mapping because the anatomic slant structure of nigrosome 1 was coherent between the axis of nigrosome 1 and the magic angle. CONCLUSIONS: The asymmetric visualization of nigrosome 1 is affected by the magic angle and susceptibility. The anatomic slant structure of nigrosome 1 causes these challenges in visualization.

Treatment of refractory non-union after maxillary osteotomy: A case report.

Maxillary non-union is a rare complication that occurs after an orthognathic surgery such as Le Fort I osteotomy. Here, we report a case of refractory non-union after maxillary osteotomy, which required a second surgery with bone graft. A 33-year-old man who had undergone bimaxillary osteotomy complained of an abnormal sensation in the right alar part about 1 year after the surgery. The patient was diagnosed as having maxillary non-union. Although surgical stabilization was performed using titanium plates, the non-union remained. The re-fusion surgery was performed about 3 years after the bimaxillary osteotomy with autologous bone graft using a biodegradable fixation system. At the 1-year follow up, the maxillary non-union was healed both clinically and radiographically. Re-fusion surgery using bone graft with biodegradable fixation might be an effective treatment option in cases of prolonged non-union that becomes evident after a long period following the initial maxillary osteotomy.

Considerations on the Factors Influencing Living Kidney Donors' Autonomous Decision-Making: A Systematic Literature Review.

As outcomes of organ transplantation have improved with advances in medicine, managing medical ethics issues has become increasingly more important. Although a basic consensus has been formed on the respect of autonomy in decision-making by prospective donors regarding living kidney transplantation, concrete and practical measures at the clinical site are required to ensure donor autonomy. The aim of the study was to identify elements related to autonomy in the kidney donor decision-making process. METHODS: We systematically collected relevant studies from multiple databases in and out of Japan and conducted qualitative and inductive analyses. RESULTS: The identified elements were categorized into 12 subcategories and then regrouped into the following 4 categories based on the similarity of the contents: donor personality and values, inability to fully understand the implications of donation, possibility of direct pressure on donor's decision-making process, and donor's environment and situation. DISCUSSION: The autonomy-related elements were highly diverse, including obvious pressure upon the donor and their values as well as influences from health care professionals. Some elements had room for change, such as the informed consent procedure, while some elements were unchangeable. Other elements were changeable by intervention, but discussion is required about the appropriateness of the intervention itself. Further, a classification of clinical approach was suggested by the development of an analytical framework using 2 axes of "site where the element arises" and "room for change" based on the practical viewpoint of clinical circumstances.

Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab.

Essentials The activated partial prothrombin time (aPTT) cannot predict the activity of emicizumab (Emi). Adjusted clot waveform analyses using a prothrombin time (PT)/aPTT initiator were developed. Activity of Emi in the co-presence of factor VIII or bypassing agents was quantified. This assay is useful for assessing coagulation potential in Emi-treated hemophilia A. SUMMARY: Background Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function. Emicizumab does not require activation by thrombin, and its effect on shortening the activated partial thromboplastin time (APTT) is much greater than that of FVIII. Therefore, the APTT has limited utility in hemophilia A (HA) patients treated with emicizumab. Aim To evaluate the global coagulation potential of emicizumab. Methods Clot waveform analysis (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define hemostatic monitoring protocols in HA patients. A modified parameter, adjusted-|min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance were defined as 100% and 0% in the precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated as an index of the maximum velocity of the coagulation process. Results Ad|min1| obtained with mixed-trigger reagent (PT/APTT/buffer, 1 : 15 : 135) in the presence of emicizumab optimally corresponded to the conversion rate estimated in animals; 0.2-0.4 IU dL-1 equivalent FVIII per 1 µg mL-1 emicizumab). Ex vivo addition of emicizumab to HA plasma with or without inhibitors resulted in concentration-dependent increases in Ad|min1|, with some individual variations. The addition of various concentrations of FVIII to HA plasma mixed with emicizumab resulted in dose-dependent increases in Ad|min1|. Similarly, mixtures of activated prothrombin complex concentrate and emicizumab added to HA plasma resulted in dose-dependent increases in Ad|min1|. In contrast, enhanced coagulation potential appeared to be better defined by the clot time than by Ad|min1| in experiments using recombinant activated FVII. Conclusion The PT/APTT reagent-triggered adjusted CWA could provide a useful means of assessing global coagulation potential in emicizumab-treated HA patients, with enhanced activity neither masking nor being masked by FVIII or bypassing agents.

Clot waveform analysis using CS-2000i™ distinguishes between very low and absent levels of factor VIII activity in patients with severe haemophilia A.

INTRODUCTION: A recently developed method to assess comprehensive coagulation function, clot waveform analysis (CWA), accurately detect low levels (<1 IU/dL) of factor VIII activity (FVIII:C) in haemophilia A patients (HA-pts). Improvements are needed, however, to differentiate patients with very low from absent levels of FVIII:C. AIM: We attempted to optimize CWA using the coagulation analyser CS-2000i™ to distinguish between very low levels and absent FVIII:C in severe HA-pts. METHODS AND RESULTS: Activated partial thrombin time (aPTT)-based clot waveforms were determined in FVIII-deficient plasmas mixed with various amounts of recombinant FVIII. Clot times (CT) were shortened, and maximum coagulation velocity (|min1|) and acceleration (|min2|) were increased in FVIII dose-dependently at levels ranging from 0.25 to 100 IU/dL. The lowest level of FVIII:C detected was 0.25 IU/dL. Plasma samples from modestly severe (MS-HA; 0.5-<1.0 IU/dL), very severe (VS-HA; 0.25-<0.5 IU/dL), extremely severe (ES-HA; <0.25 IU/dL) and inhibitor-positive HA-pts (HA-inh) were examined. The CT was markedly prolonged in all instances but showed significant differences between the different groups insufficiently. The |min1| and |min2| in HA-inh were lower compared to the other groups (P<.05). A new parameter (slope-|min1|) reflecting average coagulation acceleration was derived. This index (median) was lower in HA-inh (0.0042) compared to ES-HA (0.0068) and VS-HA (0.011) with greater significant differences (P<.01), and an index of <.005 reflected the total absence of FVIII in the presence of inhibitor. CONCLUSION: The slope-|min1| parameter could provide a useful index for evaluating very low and absent levels of FVIII and/or the development of FVIII inhibitor in HA-pts.

Ventilatory and behavioural responses of the marbled sole Pseudopleuronectes yokohamae to progressive hypoxia.

This study identified ventilatory and behavioural responses in the marbled sole Pseudopleuronectes yokohamae under experimentally induced progressive decreases in dissolved oxygen (DO) levels. Ventilation frequency showed an increase with decreasing DO levels from normoxia to 2·75 mg O2 l-1 , followed by a decrease in ventilation frequency at decreased DO levels from 2·00 to 0·75 mg O2 l-1 . At DO levels below 2·00 mg l-1 , behaviours at the bottom were suppressed, whereas avoidance behaviours increased. A decrease in avoidance behaviours was observed from 1·00 to 0·75 mg O2 l-1 . Upside-down reversal and incapacitation at DO levels of 1·00-0·75 mg O2 l-1 suggested that sublethal effects on P. yokohamae were induced. The responses observed before the sublethal DO level could be interpreted as an effort to maintain oxygen uptake, reduce routine activities and facilitate avoidance. The observed DO level thresholds that induce behavioural responses, in addition to sublethal effects, indicate hypoxia-tolerance that is important for understanding the effects of hypoxia on coastal ecosystems.

In vitro synergistic effects of zoledronic acid and calcium on viability of human epithelial cells.

OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw is a common complication with defective wound healing of oral mucosa and frequently occurs in patients receiving zoledronic acid (ZA). The aim of this in vitro study was to investigate whether ZA has a cytotoxic effect at clinically relevant concentrations on epithelial cells when calcium conditions are altered. METHODS: HaCaT human keratinocyte cells were treated with ZA in the presence of various concentrations of calcium. The concentrations of ZA included submicromolar ones, which are comparable with those found in the plasma of patients. Cell viability and apoptosis were assessed using MTT assay and annexin V flow cytometry. RESULTS: Under standard culture conditions, cell growth was inhibited at 1 µM of ZA or above, but was unaffected by lower concentrations. However, when calcium concentrations were moderately increased, cell viability was decreased and apoptosis was induced at 0.2-0.3 µM of ZA. Moreover, a 50% reduction in serum in the hypercalcemic medium resulted in a significant decrease in cell viability at a much lower concentration (0.05 µM). CONCLUSION: These results suggest that clinically relevant concentrations of ZA, which alone have little effects, can be toxic to the epithelial cells depending on the conditions of extracellular calcium.

Central cystadenocarcinoma of the mandible.

Papillary cystadenocarcinoma (PCAC) of the salivary gland is a rare malignant tumour and occurs in major and minor salivary glands. PCAC of the mandible is exceptionally rare; only 2 cases have been reported. In this study, the authors report a case of PCAC within the mandible. The patient presented with a painful right mandibular mass that had gradually increased in size. The lesion appeared radiographically as a well-demarcated multilocular radiolucent area, similar to an odontogenic cystic lesion. The authors present a case of PCAC with reference to the relevant literature.

The N-terminal amino acid of apolipoprotein D is putatively covalently bound to 3-hydroxy-3-methyl hexanoic acid, a key odour compound in axillary sweat.

Axillary sweat is odourless when freshly collected at the surface of human skin, but it contains non-odoriferous precursors, which can be transformed into odorous substances by bacteria. E-3-methyl-2-hexanoic acid (3M2H) is one of the key odorous substances, but there are two contradictory reports about its precursor form. One report states that 3M2H linked non-covalently to apolipoprotein D (apoD) is the precursor, while a second report states that 3M2H-Gln identified in human axillary sweat is the precursor. Recently, 3-hydroxy-3-methyl hexanoic acid (HMHA) and 3-methyl-3-sulfanylhexane-1-ol (3M3T) have also been identified and reported as characteristic components found in apocrine sweat. To better understand the formation of axillary odours and the structural relationships between these compounds and apoD, we characterized the linkage between odorous substances and apoD in human axillary secretions. ApoD was purified from human axillary secretions collected from 50 healthy female volunteers and was then digested by trypsin and analysed by MALDI-TOF mass spectrometry. A Mascot search showed that 8 peaks identified in the trypsin-digested samples correspond to the masses calculated for theoretically digested apoD sequences and the purified protein was assigned as a precursor of apoD [Homo sapiens]. One spectrum corresponded to the theoretical peak of HMHA linked covalently to the N-terminal fragment of apoD. In contrast, no spectrum corresponded to the theoretical peak of a 3M2H adduct or to an unmodified N-terminal fragment of apoD. These results indicate a possibility that HMHA binds covalently to the N-terminal amino acid of apoD in human axillary secretions.

Radiologic and neuropathologic findings in patients in a family with dentatorubral-pallidoluysian atrophy.

We describe the cases of 2 patients, a father and his son, with DRPLA who underwent MR examinations prior to death and in whom postmortem examinations of the brain were obtained. MR imaging findings had the following features: 1) atrophy of the cerebellum and brain stem were the common findings, 2) high-signal-intensity lesions in the cerebral white matter and brain stem were observed on T2-weighted images in the patient with adult-onset DRPLA, 3) signal-intensity changes in the cerebral white matter were restricted to the periventricular white matter in the patient with juvenile-onset DRPLA, but these changes appear in the advanced stage, and 4) progressive cerebral atrophy was more marked in the patient with juvenile-onset DRPLA. In the patients with DRPLA, the abnormal high signal intensity of the cerebral white matter or brain stem on MR images reflect the loss of myelinated fibers. Cerebral atrophy mainly reflects atrophy of the neuropile.

Effects of a tropical cyclone on the distribution of hatchery-reared black-spot tuskfish Choerodon schoenleinii determined by acoustic telemetry.

The effects of a tropical cyclone on the distribution of hatchery-reared black-spot tuskfish Choerodon schoenleinii were examined using acoustic telemetry. Nine fish were released in Urasoko Bay, Ishigaki Island, Japan, in September 2006, and another nine were released in June to July 2007, before a cyclone's passing through the area in September 2007. Data for the fish released in 2006 were used as the cyclone-inexperienced group to compare their distribution pattern to that of the 2007 cyclone-experienced group. Both groups of fish were monitored for up to 150 days. Of the nine fish in each group, four (44%) and two (22%) were monitored for over 150 days in the cyclone-inexperienced and the cyclone-experienced groups, respectively. Three of the five fish that had settled in the monitoring area left the area within a few days of the cyclone event. To estimate the time of disappearance of the fish, maximum wind speed during a period of 7 days (indicating the occurrence and intensity of the tropical cyclone), fish size and release year were evaluated as explanatory variables using a Cox proportional hazards model with Akaike's information criterion. The best predictive model included the effect of maximum wind speed. One fish that left the monitoring area displayed movement patterns related to strong winds, suggesting that wind-associated strong currents swept the fish away. No relationships were found between the movement patterns of the other two fish and any physical environmental data. The daily detection periods of one of the two fish gradually decreased after the cyclone hit, and this fish eventually left the monitoring area within 3 days, suggesting that it shifted to a habitat outside the monitoring area. These results indicate that tropical cyclones have both direct and indirect effects on the distribution of hatchery-reared C. schoenleinii.

Self-organized nanodot pattern fabrication using the reverse sputtering method.

We demonstrate the synthesis of high density periodic 2D nanodot patterns using reverse sputtering in magnetron sputtering equipment on a single crystal Si substrate and sputter-deposited Si-thin film. In this etching process, a minute amount of Ta is supplied by DC sputtering or splashing from the substrate holder surface. STEM, EDX, TEM and XPS analyses confirmed preferentially localized Ta-silicide in the nanodots. The nanodot pattern formation is attributed to the repeated adsorption and desorption of Ta and Si molecules forming Ta-silicide, and its segregation with self-organization. We also discuss power and time dependence of the nanodot pattern sizes and hole structure formation as a side-effect. This simple process is conducted at room temperature and makes use of an extremely simple setup. Our result promises a significant improvement in the productivity of quantum dot devices and has the potential to trigger their worldwide spread.

Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice.

Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro. On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human NE. Bronchoalveolar lavage fluid (BALF) and lung sections were analysed on days 8, 11 and 14. The effect of late administration of tiotropium on the goblet cell metaplasia by NE aspiration was also assessed. NE-induced MUC5AC production by NCI-H292 cells was measured with ELISA. Repeated NE aspiration induced marked goblet cell metaplasia. The grading of goblet cell metaplasia, neutrophil count and eosinophil count in BALF, keratinocyte-derived chemokine level and leukotriene B(4) level in BALF, and M(3) receptor expression by immunohistochemistry, were lower in the tiotropium group than in the vehicle group. Late administration of tiotropium inhibited the established goblet cell metaplasia. Tiotropium inhibited NE-induced MUC5AC production. Tiotropium inhibited NE-induced goblet cell metaplasia and mucin production, probably mediated by suppression of inflammation and a direct action on epithelial cells. This result suggests that tiotropium may be useful for the treatment of mucus overproduction in COPD.

Effect of the preliminary hydration on gastric emptying time for water in healthy volunteers.

BACKGROUND: International guidelines allow healthy patients to drink clear liquid up to 2 h before general anesthesia. Recently, MRI measurements have been used for tracking gastric volume in humans. Hence, we used MRI to examine the gastric emptying rate of water in healthy volunteers with or without prior water loading. METHODS: Fifteen healthy volunteers were enrolled. The participants had MRI examinations on separate days under two different protocols: The preliminary hydration protocol (group H) and the water restriction protocol (group R). After the intake of water, MR imaging was performed every 10 min for 60 min. The gastric content was outlined as area of interest (AOI), and the AOI area of each slice was summated to calculate the volume of gastric contents. RESULTS: The 50% reduction time of gastric volume in group R and group H was 18+/-9 and 16+/-8 min (mean+/-SD), respectively. There were no significant changes between the two groups. CONCLUSION: The gastric emptying time for water evaluated with MRI was not affected by preliminary hydration, which shows the safety of repeated oral hydrations in the pre-operative period.

Difference in intracortical inhibition of the motor cortex between cortical myoclonus and focal hand dystonia.

OBJECTIVE: The short interval intracortical inhibition (SICI) of the motor cortex (M1) is reduced in both cortical myoclonus and focal hand dystonia. This reduction has been attributed to the dysfunction of GABAergic system within the motor cortex. However, the precise mechanisms underlying the reduction may not be entirely identical in these two disorders, being due to primary pathological involvement in M1 or secondary to functional changes outside M1. The aim of this study was to elucidate possible differences in intracortical inhibition between these two disorders. METHODS: Subjects were 11 patients with benign myoclonus epilepsy, 7 with focal hand dystonia, and 11 normal volunteers. We studied SICI using anterior-posterior (AP) directed and posterior-anterior (PA) directed induced currents in the brain. RESULTS: In both disorders, SICI with PA-directed currents was reduced as reported previously. In contrast, SICI studied with AP currents was normal in patients with focal hand dystonia, but reduced in patients with cortical myoclonus. CONCLUSIONS: The difference between the two disorders might reflect the underlying pathological difference. In cortical myoclonus, the inhibitory interneurons of the motor cortex are affected, whereas the same interneurons are intact in dystonia. The difference in SICI induced by AP and PA directed currents in dystonia may be explained by the following possibilities: the difference in composition of I-waves contributing to EMG generation and the difference in modulation of the interneuronal activity by voluntary contraction. These changes may be secondary to dysregulation of the motor cortex by the basal ganglia or related cortices in dystonia. SIGNIFICANCE: The SICI using AP directed currents together with the conventional SICI using PA directed currents was able to demonstrate some difference in the intrinsic circuits of M1 between myoclonus and focal hand dystonia. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.

Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation.

OBJECTIVE: To assess corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS) by correlating diffusion tensor imaging (DTI) measures with intra- and extracranial central motor conduction time (CMCT) and clinical features of the patients. METHODS: We investigated 31 patients with ALS and 31 normal volunteers by DTI and measured fractional anisotropy (FA) within the corticospinal tracts and in the extramotor white matter. We measured CMCT for the first dorsal interosseous muscle and segmented it into cortical-brainstem (CTX-BS CT) and brainstem-cervical root (BS-CV CT) conduction times by magnetic brainstem stimulation at the foramen magnum level. Clinical status of each patient was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and upper motor neuron (UMN) score devised for this study. RESULTS: We found a significant decrease of mean FA in all regions of the corticospinal tracts in patients with ALS as compared with controls. We found that FA along the corticospinal tract decreased significantly with higher UMN scores. There was no significant correlation between FA and ALSFRS-R, to which both upper and lower motoneuron involvements contribute. FA showed a significant correlation with the intracranial part of the central motor conduction (CTX-BS CT) but not with the extracranial conduction time. CONCLUSIONS: Fractional anisotropy reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of upper motor neuron impairment in amyotrophic lateral sclerosis.

Ceramide and adenosine 5'-monophosphate-activated protein kinase are two novel regulators of 11beta-hydroxysteroid dehydrogenase type 1 expression and activity in cultured preadipocytes.

Increased activity of intracellular glucocorticoid reactivating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in obese adipose tissue contributes to adipose dysfunction. As recent studies have highlighted a potential role of preadipocytes in adipose dysfunction, we tested the hypothesis that a variety of metabolic stress mediated by ceramide or AMP-activated protein kinase (AMPK) would regulate 11beta-HSD1 in preadipocytes. The present study is the first to show that 1) expression of 11beta-HSD1 in 3T3-L1 preadipocytes was robustly induced when cells were treated with cell-permeable ceramide analogue C(2) ceramide, bacterial sphingomyelinase, and sphingosine 1-phosphate, 2) 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced activation of AMPK augmented the expression and enzyme activity of 11beta-HSD1, and 3) these results were reproduced in human preadipocytes. We demonstrate for the first time that C(2) ceramide and AICAR markedly induced the expression of CCAAT/enhancer-binding protein (C/EBP) beta and its binding to 11beta-HSD1 promoter. Transient knockdown of C/EBPbeta protein by small interfering RNA markedly attenuated the expression of 11beta-HSD1 induced by C(2) ceramide or AICAR. The present study provides novel evidence that ceramide- and AMPK-mediated signaling pathways augment the expression and activity of 11beta-HSD1 in preadipocytes by way of C/EBPbeta, thereby highlighting a novel, metabolic stress-related regulation of 11beta-HSD1 in a cell-specific manner.