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Exosomes are potent players in the development of metastases and they play an important role in cancer angiogenesis and exacerbation. However, it is unclear how proteins on exosomes affect development of blood vessel networks. In this study, we focused on relationships between membrane proteins on exosomes and angiogenesis using human umbilical vein endothelial cells (HUVEC). Lung tumor cell-derived exosomes induced tube formation and growth of endothelial cells in vitroin a dose-dependent manner involving MAPK activation, but this was not seen in normal lung epithelial cells. Ephrin type-A receptor 2 (EphA2) was identified by proteomic analysis and an inhibition assays showed it is a major MAPK activator on exosomes. Thus EphA2 on exosomes participates in angiogenesis as a ligand of the ephrin signaling pathway. These results support the development of novel therapeutic strategies such as blockade of remote cancer communications through exosomes.

At the present, the grid-tied solar power system is the most promising as a renewable energy technology for replacing the fossil energy sources. The usage efficiency of the power conditioner system in the grid-tied solar power system is not high because the electricity generation from solar panels depends on the weather. The utilization rate of the power conditioner system can be increased by adding the small scale wind turbine to the existing grid-tied solar power system. We introduced a novel design solution in the previous study to connect the small wind turbine with the power conditioner system of the grid-tied solar power system by emulating technical characteristics of the solar panel in series connection mode. By which, the utilization rate of the power conditioner system has been increased. However, this improved utilization rate of the power conditioner system is not high in the cloudy and rainy days because the voltage of the solar panel changes slightly and the maximum input voltage of the power conditioner system is limited. Therefore, we propose a novel performance enhancement method for solar–wind hybrid power plant using photovoltaic cell emulating system in this research.

AimsThe aims of this study were to evaluate the morphology of the ankle in patients with an osteochondral lesion of the talus using 3D CT, and to investigate factors that predispose to this condition.Patients and MethodsThe study involved 19 patients (19 ankles) who underwent surgery for a medial osteochondral lesion (OLT group) and a control group of 19 healthy patients (19 ankles) without ankle pathology. The mean age was significantly lower in the OLT group than in the control group (27.0 vs38.9 years; p = 0.02). There were 13 men and six women in each group. 3D CT models of the ankle were made based on Digital Imaging and Communications in Medicine (DICOM) data. The medial malleolar articular and tibial plafond surface, and the medial and lateral surface area of the trochlea of the talus were defined. The tibial axis-medial malleolus (TMM) angle, the medial malleolar surface area and volume (MMA and MMV) and the anterior opening angle of the talus were measured.ResultsThe mean TMM angle was significantly larger in the OLT group (34.2°, sd4.4°) than in the control group (29.2°, sd4.8°; p = 0.002). The mean MMA and MMV were significantly smaller in the OLT group than in the control group (219.8 mm2, sd42.4) vs(280.5 mm2, sd38.2), and (2119.9 mm3, sd562.5) vs(2646.4 mm3, sd631.4; p < 0.01 and p = 0.01, respectively). The mean anterior opening angle of the talus was significantly larger in the OLT group than in the control group (15.4°, sd3.9°) vs(10.2°, sd3.6°; p < 0.001).Conclusion3D CT measurements showed that, in patients with a medial osteochondral lesion of the talus, the medial malleolus opens distally, the MMA and MMV are small, and the anterior opening angle of the talus is large. This suggests that abnormal morphology of the ankle predisposes to the development of osteochondral lesions of the talus.Cite this article: Bone Joint J2018;100-B:1487–90.

AimsThe aims of this study were to analyse the long-term outcome of vascularised fibular graft (VFG) reconstruction after tumour resection and to evaluate the usefulness of the method. Patients and MethodsWe retrospectively reviewed 49 patients who had undergone resection of a sarcoma and reconstruction using a VFG between 1988 and 2015. Their mean follow-up was 98 months (5 to 317). Reconstruction was with an osteochondral graft (n = 13), intercalary graft (n = 12), inlay graft (n = 4), or resection arthrodesis (n = 20). We analysed the oncological and functional outcome, and the rate of bony union and complications.ResultsFive- and ten-year overall survival rates were 89% and 86%, respectively. Local recurrence occurred in two patients. Eight patients developed pulmonary metastases. Bone union was achieved in 44 patients (90%). Fracture occurred in six patients (12%), infection in three (6%), and nonunion in five (10%). The mean Musculoskeletal Tumor Society (MSTS) scores were as follows: osteochondral graft 70%; intercalary graft 73%; inlay graft 89%; and resection arthrodesis 83%.ConclusionAlthough associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome.Cite this article: Bone Joint J2017;99-B:1237–43.

In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0–7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110–149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24). The median follow-up was 2.7 years. Patients in the moderate/severe hyperglycemia group had significantly worse characteristics. The cumulative incidences of 2-year non-relapse mortality (NRM) and the probabilities of 2-year overall survival (OS) in the normoglycemia, mild hyperglycemia and moderate/severe hyperglycemia groups were 7.5%, 19% and 29%, respectively (P<0.01), and 69%, 53% and 33%, respectively (P<0.01). In multivariate analyses, hyperglycemia was an independent predictor of high NRM (vs normoglycemia; mild hyperglycemia, hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.56–4.18; moderate/severe hyperglycemia, HR 4.46, 95% CI 1.92–10.3) and poor OS (vs normoglycemia; mild hyperglycemia, HR 1.54, 95% CI 1.14–2.07; moderate/severe hyperglycemia, HR 1.61, 95% CI 0.89–2.91). In conclusion, hyperglycemia on days 0–7 after allo-SCT was associated with inferior outcomes.

Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus—conserved across mice and humans—contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3'-untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome.

The seizure resistance in the ironing process of stainless steel cups was improved with lubricants containing Al2O3particles, and the ironing limit of the cups was increased. The effects of suspending different concentrations of Al2O3particles in paraffin based oils on increasing the ironing limit of SUS430 cylindrical cups before seizure were investigated using a lapped tungsten carbide die. By containing c= 2vol% of Al2O3particles having nominal diameter dbetween 0.02 to 4 micrometres in an oil with a kinematic viscosity of 500 mm2/s, the ironing limit of the cup was 8% under a punch speed of 100 mm2/s. The limit was similar to the limit using a commercial low-viscosity oil with chlorine additive. The kinematic viscosity of the base oil was reduced. In d= 0.2 μm and c= 0.5vol%, the limit of the oil more than kinematic viscosity of 180 mm2/s was similar to the limit by the commercial oil. In d= 4 μm and c= 1vol%, the limit of the oil having more than kinematic viscosity of 100 mm2/s was effective. It was found that the seizure resistance in the ironing process was improved by the proper ironing conditions with lubricants containing particles.

Context. A comprehensive framework for comparing spectral data from different planets has yet to be established. This framework is needed for the study of extrasolar planets and objects within the solar system.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has curative potential against hematological malignancies. However, there are concerns about the associated risk of non-relapse mortality (NRM). We performed a retrospective single-center study to assess changes in outcomes after allo-HSCT and causes of NRM over three 5-year periods. The rates of 2-year NRM and overall survival (OS) were 16% and 59%, respectively. We found a significant decrease in NRM (P<0.001), with 2-year NRM of 26, 14 and 9%, and a significant increase in OS (P=0.005), with 2-year OS of 52%, 58% and 65%, over the three periods (1998–2002, 2003–2007 and 2008–2012), respectively. Of note, a steady improvement was observed in NRM, period by period, among patients aged 50 years or older, patients who underwent HSCT from an unrelated bone marrow donor and patients who underwent HSCT with a reduced-intensity conditioning regimen. Our data showed that the improved NRM can mainly be attributed to a decreased mortality related to infection after starting systemic steroid as GVHD treatment, and a decreased mortality related to organ failure.

In order to realize advanced self-driving car, a high-speed and high-reliability network connecting surrounding monitoring sensors and artificial intelligence and control area systems is necessary [1]. As for their communication protocol, "Automotive Ethernet" is the favorite and standardization activities are proceeding at IEEE, ISO and IEC. We are participating in this standardization activity and are in charge of building a simulator for communication performance evaluation. In our presentation, we will introduce the trend of Automotive Ethernet standardization and simulation technology developed for automotive application. [ABSTRACT FROM AUTHOR]

We have studied the CDW transport in different mesoscopic structures with size variation from the micro to the nanometer scale. The structures of three types, all based on thin NbSe3crystals, were investigated : 1) periodic system of antidots (holes) with size and spacing variation from micron to the submicron scale, 2) randomly distributed columnar defects (CDs) of various concentration with diameter of 16 nm, 3) short bridges across the conducting bc-planes with the length of 30-50 nm. We report here a number of new features of the CDW transport in mesostructures, in particular, non-linear properties of submicron network, the experimental evidence of quantum interference effect of sliding CDW on CDs threaded by magnetic flux, zero bias conductance peak in the a*-axis transport.

We studied the interlayer tunneling in Bi-2212 stacks with in plane size variation down to submicron size. For submicron junctions we found experimental evidence of Coulomb charging effcts. The Coulomb blockade leads to the drop down of the Josephson critical current density and to appearance of periodic Coulomb staircase structure of current peaks on the IV characteristics. The period of the structure corresponds to the charge energy of the single Cooper pair charge soliton including the total number of the elementary junctions in the stack (~ 50). We analyzed conditions of the existence of charging effects in layered high-Tcmaterials of Bi-2212 type.

Distinctive "flickering" movements are observed in TEM images of the microstructure of Cu-Mn alloys after aging within the miscibility gap. Analyses of two-beam image extinction and electron diffraction streaks indicate that the underlying tweed and "V-shaped" images involve a static displacement field of the type {110} <1-10>. Atomic force microscopy and other microanalyses show the presence of Mn-enriched colonies of 15-40 nm, formed throughout the microstructure, in which twinned fct crystallites are induced and confined. The flickering movements are interpreted as a direct manifestation of the fcc→fct transformation event and in particular of a rotation of the fct c-axis, these effects being caused by an inelastic interaction between <110> <1-10> phonons and the accelerated electrons of the incident TEM beam.

Time-dependent dielectric breakdown (TDDB) measurement of MOS capacitors on an n-type 4 ° off-axis 4H-SiC(0001) wafer free from step-bunching showed specific breakdown in the Weibull distribution plots. By observing the as-grown SiC-epi wafer surface, two kinds of epitaxial surface defect, Trapezoid-shape and Bar-shape defects, were confirmed with confocal microscope. Charge to breakdown (Qbd) of MOS capacitors including an upstream line of these defects is almost the same value as that of a Wear-out breakdown region. On the other hand, the gate oxide breakdown of MOS capacitors occurred at a downstream line. It has revealed that specific part of these defects causes degradation of oxide reliability. Cross-sectional TEM images of MOS structure show that gate oxide thickness of MOS capacitor is non-uniform on the downstream line. Moreover, AFM observation of as-grown and oxidized SiC-epitaxial surfaces indicated that surface roughness of downstream line becomes 3-4 times larger than the as-grown one by oxidation process.

Triangular shaped defects with obtuse-angles at tops and long bases are often observed in surfaces of epitaxial films. We have investigated the origins of them, and it became clear that these defects without clear origins were formed by contaminations of tantalum carbide particles. Formations of micro-order pipes at the origin points of these defects were also observed. These micro-order pipes did not accompany strain and dislocations around them, though their appearances were very similar to the ones so-called micro-pipes.

Experimentally,the grazing-incident X-ray topography at different diffraction conditions, and room temperature photo-luminescence spectroscopy, various different types of stacking-faults in epitaxial films on 4-degrees-off 4H-SiC wafers were identified precisely without wafer cutting. Their types and the numbers were investigated statistically. It became clear that (4,4) type stacking-faults were the most common ones and two different types were identified. Still 34% of the stacking-faults were unknown types in the present investigation.Several different kinds of stacking-faults formed on the surface of 4-degrees-off 4H-SiC epitaxial wafers were investigated. Their types could be identified and type distribution in a wafer could be obtained using X-ray topography and room temperature Photo-Luminescence without wafer cutting. Type determination of 8H(4,4)- stacking fault ; with or without strain field, could also be decideddemonstrated using this method.

Second-harmonic-generation (SHG) microscopy is useful to visualize collagen fiber in biological tissues in vivo. In this paper, we applied our SHG microscopy equipped with a Cr:Forsterite laser to visualize human dermal collagen fiber in vivo. The obtained SHG images indicated the structural difference of dermal collagen fiber between different ages, for example, fine collagen fiber is densely distributed in 20's subjects whereas only thick collagen fiber is remained in 60's subjects. These results reflect structural change of collagen fiber caused by natural aging and/or photoaging. The SHG microscopy has a potential to become an in vivo collagen-sensitive microscopy for assessment of skin aging.

Familial amyloid polyneuropathy (FAP), which is a fatal disorder inherited in an autosomal dominant fashion, is characterized by systemic accumulation of polymerized transthyretin (TTR) in the peripheral nerves and systemic organs. Liver transplantation has become an accepted treatment of this disorder because it stops the major production of amyloidogenic TTR. However, improved survival of transplant patients compared with that of nontransplant patients has not been sufficiently demonstrated. This study investigated whether transplantation improved the long-term outcome of patients by comparing the survival of patients who had transplantations with that of patients who had not had transplantations.

Total hip replacement for high dislocation of the hip joint remains technically difficult in terms of preparation of the true acetabulum and restoration of leg length. We describe our experience of cementless total hip replacement combined with a subtrochanteric femoral shortening osteotomy in 20 hips with Crowe grade IV dislocation with a mean follow-up of 8.1 years (4 to 11.5). There was one man and 17 women with a mean age of 55 years (44 to 69) at the time of the operation.After placment of the acetabular component at the site of the natural acetabulum, a cementless porous-coated cylindrical femoral component was implanted following a subtrochanteric femoral shortening osteotomy.The mean Japanese Orthopedic Association hip score improved from a mean of 38 (22 to 62) to a mean of 83 points (55 to 98) at the final follow-up. The mean lengthening of the leg was 14.8 mm (-9 to 34) in patients with iliofemoral osteoarthritis and 35.3 mm (15 to 51) in patients with no arthritic changes. No nerve palsy was observed.Total hip replacement combined with subtrochanteric shortening femoral osteotomy in this situation is beneficial in avoiding nerve injury and still permits valuable improvement in inequality of leg length.

We undertook a prospective study to evaluate the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma. The levels were measured by an enzyme-linked immunosorbent assay in 15 patients with osteosarcoma before commencing treatment. The patients were divided into two groups, with a high or a low serum VEGF level, and the incidence of metastases and overall survival rate were compared.No significant relationship was observed between the serum VEGF levels and gender, age, the size of the tumour or the response to pre-operative chemotherapy. Patients with a serum VEGF > 1000 pg/ml had significantly worse survival than those with a level < 1000 pg/ml (p = 0.002). The serum VEGF level may be useful in predicting the prognosis for survival in patients with osteosarcoma.

Context. Massive young stellar objects?(MYSO) are surrounded by massive dusty envelopes, whose physical structure and geometry are determined by the star formation process.Aims. Our principal aim is to establish the density structure of MYSO envelopes on scales of ~1000?AU. This constitutes an increase of a factor ~10 in angular resolution compared to similar studies performed in the (sub)mm.Methods. We have obtained diffraction-limited (0.6??) 24.5??m?images (field of view of 40??30?) of 14 well-known massive star formation regions with the COMICS instrument mounted on the 8.2?m Subaru telescope. We construct azimuthally averaged intensity profiles of the resolved MYSO envelopes and build spectral energy distributions?(SEDs) from archival data and the COMICS 24.5??m?flux density. The SEDs range from near-infrared to millimeter wavelengths. Self-consistent 1-D radiative transfer models described by a density dependence of the form n(r) ?r-pare used to simultaneously compare the intensity profiles and SEDs to model predictions.Results. The images reveal the presence of discrete MYSO sources which are resolved on arcsecond scales, and, to first-order, the observed emission is circular on the sky. For many sources, the spherical models are capable of satisfactorily reproducing the 24.5??m?intensity profile, the 24.5??m??flux density, the 9.7??m?silicate absorption feature, and the submm emission. They are described by density distributions with p =1.0?0.25. Such distributions are shallower than those found on larger scales probed with single-dish (sub)mm studies. Other sources have density laws that are shallower/steeper than p=1.0 and there is evidence that these are viewed near edge-on or near face-on respectively. In these cases spherical models fail to provide good fits to the data. The images also reveal a diffuse component tracing somewhat larger scale structures, particularly visible in the regions S?140, AFGL?2136, IRAS?20126+4104, Mon?R2, and Cep?A.Conclusions. We find a flattening of the MYSO density law going from scales probed with single-dish submm observations down to scales of ~1000?AU probed with the observations presented here. We propose that this may be evidence of rotational support of the envelope. This finding will be explored further in a future paper using 2-D axisymmetric radiative transfer models.

We evaluated triple-phase bone scintigraphy in the differential diagnosis of peri-prosthetic infection in 46 patients with a total hip replacement or bipolar hemiarthroplasty who were due for revision surgery. There were 18 men and 28 women, with a mean age at operation of 64.6 years (28 to 81). We defined peri-prosthetic infection as an increased uptake of radioisotope in all the phases of triple-phase bone scintigraphy and validated these results against the histological and/or microbiology results in every case.The positive and negative predictive values for the presence of infection were 83% and 93%, respectively. The diagnostic sensitivity was 88% and the specificity was 90%.This study indicates that triple-phase bone scintigraphy is a useful tool in the detection of peri-prosthetic infection and offers a cost-effective method of screening.

It is now widely believed that tumors originate from normal cells as a result of accumulated genetic/epigenetic changes. These alterations affect the signaling pathways at transcriptional and post-transcriptional level that drive cells into uncontrolled cell division, growth, and migration. Recent advancement of molecular technologies have yielded comprehensive gene expression profiling techniques that have successfully provided candidate diagnostic and prognostic markers in human cancers. Serial Analysis of Gene Expression (SAGE) is a technology to facilitate the measurement of mRNA transcripts of normal and malignant tissues in a non-biased and highly accurate and quantitative manner. SAGE produces a comprehensive gene expression portrait without a priori gene sequence information, leading to the identification of novel transcripts potentially involved in the pathogenesis of human cancer. In this review, we provide a brief outline of SAGE to underscore the advantages of the method relative to the other gene expression profiling approaches in cancer research. We also summarize the progression of recent gene expression profiling studies and discuss the current topics of SAGE analysis in cancer research for the development of novel therapeutic interventions.

Patients with amyloidogenic transthyretin (ATTR) Tyr114Cys develop amyloid deposits in cerebral blood vessels, cerebral hemorrhage, and rapidly progressive dementia that presents with hereditary cerebral amyloid angiopathy (CAA). However, no treatment has been identified for CAA. Although liver transplantation has become an acceptable treatment of TTR-related amyloidosis, liver transplantation may not successfully treat CNS manifestations of the disorder. In this study, we examined the effect of liver transplantation on these manifestations of TTR-related CAA.

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation.On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 µm to 10 µm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia.The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly.We consider that the sympathetic nervous system plays an important role in the generation of radicular pain.

The effectiveness of phosphorus diffusion gettering (PDG) and related segregation coefficients for different metal impurities were measured applying thermal treatments in the temperature range 800-950 °C for different times. We used multi-crystalline and mono-crystalline CZ p-type wafers with different boron concentrations and different levels of dislocations and bulk micro-defects (BMD). In all sample types, for Cu and Ni we found complete gettering in the temperature range investigated. In the case of Fe, the segregation coefficient increases with both increase in temperature and extension of time. The increase is qualitatively changing when going above 900 °C. At 950 °C the segregation coefficient increases faster at shorter diffusion time but at extended diffusion time it increases slower as compared to diffusion at 900 °C. At the same temperature and time of phosphorus diffusion the segregation coefficient is found to be independent of the metal impurity concentration in the range of 1012-1015 cm-3 investigated. We have shown that the presence of BMD and dislocations in bulk silicon does not impede the ability of PDG to completely remove Fe, Ni and Cu metal impurities from the bulk. Further analysis suggests that the PDG has the same gettering efficiency for mono-crystalline silicon and multi-crystalline silicon. We conclude that if any bulk precipitation of Fe, Ni and Cu impurities is present in multi-crystalline silicon it cannot seriously compete with PDG. However we found that increasing the boron concentration in the samples reduces the segregation coefficient of Fe, and this reduction is more severe at lower temperatures. Finally, by applying a post anneal ramp down from 900 °C to 700 °C after phosphorus diffusion, we found that the Fe segregation coefficient increases by a factor of 36 for lightly B doped samples, from 53 to 1919, leading to a significant reduction of Fe in the bulk after 2 hours ramp down anneal.

We evaluated the construct validity of the Musculoskeletal Tumour Society rating scale (Enneking score) as a functional measure for patients with sarcoma involving the upper limb. We compared the Enneking score by examining the correlation between two patient-derived outcome measures, the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Medical Outcomes Study Short Form-36 (SF-36) as indicators of functional status in 40 patients with malignant or aggressive benign bone and soft-tissue tumours of the upper limb who had undergone surgical treatment.The frequency distributions were similar among the three scoring systems. As for the validity, Spearman’s rank correlation coefficient of the Enneking score to the DASH questionnaire was -0.79 and that of the Enneking to the SF-36 subscales ranged from 0.38 to 0.60. Despite being a measure from the surgeon’s perspective, the Enneking score was shown to be a valid indicator of physical disability in patients with malignant or aggressive benign tumours of the upper limb and reflected their opinion.

A 57-year-old woman in Japan, the first recipient of part of a liver from a 58-year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs for 3 years, started to develop sensory neuropathy 7 years after transplantation. Before the July 1998 sequential transplantation, she had been in a hepatic coma at the terminal stage of primary biliary cirrhosis and waiting for deceased donor liver transplantation. In September 2004, biopsy samples of her duodenum first showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no changes in amyloid deposition, decreased temperature sensation and pain in fingertips and toes were detected at a neurologic examination in March 2006. Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition started. Nerve conduction velocity studies revealed mild to moderate axonal sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic sensory neuropathy induced by amyloid deposition 7 years after sequential liver transplantation.

To clarify the pathomechanisms of discogenic low back pain, the sympathetic afferent discharge originating from the L5-L6 disc via the L2 root were investigated neurophysiologically in 31 Lewis rats. Sympathetic afferent units were recorded from the L2 root connected to the lumbar sympathetic trunk by rami communicantes. The L5-L6 discs were mechanically probed, stimulated electrically to evoke action potentials and, finally, treated with chemicals to produce an inflammatory reaction. We could not obtain a response from any units in the L5-L6 discs using mechanical stimulation, but with electrical stimulation we identified 42 units consisting mostly of A-delta fibres. In some experiments a response to mechanical probing of the L5-L6 disc was recognised after producing an inflammatory reaction. This study suggests that mechanical stimulation of the lumbar discs may not always produce pain, whereas inflammatory changes may cause the disc to become sensitive to mechanical stimuli, resulting in nociceptive information being transmitted as discogenic low back pain to the spinal cord through the lumbar sympathetic trunk. This may partly explain the variation in human symptoms of degenerate discs.

Single-crystal whiskers of Eu-123 were grown from Te and Ca doped precursor pellets. The Eu-123 whiskers contained a certain amount of Ca but were not contaminated with Te. Our composition analysis and superconducting property measurements reveal that the whiskers inherited certain site disorders and oxygen deficiencies in the as-grown state, which is reflected in the very low Tc. High pressure oxygen annealing was required to increase the Tcto about the 80 K level. Submicron sized junctions fabricated by focused ion-beam etching showed clear multi-branch structure with hysteresis in the I-Vcurve. The Eu-123 whiskers were found to possess excellent crystalline quality both in the as-grown state and after high pressure annealing, despite the site disorders. The critical current density Jcof a Eu-123 whisker (Tc= 45 K) was estimated to be 1.43 × 105A cm?2at 4.2 K, twice that observed for Y-123 having a similar Tc.

p63 is critical for squamous development and exists as multiple isotypes of two subclasses, TA and ΔN. ΔNp63 isotypes can antagonize transcription by TAp63 and p53, and are highly expressed in squamous cell cancers. Using mouse keratinocytes as a biological model of squamous epithelium, we show that multiple p63 isotypes, ΔN- and TA-containing, are expressed and differentially modulated during in vitro murine keratinocyte differentiation. ΔNp63α declines with Ca2+-induced differentiation, while a smaller ΔN-form, ΔNp63s, persists, suggesting unique functions of the two ΔN-forms. To investigate the impact of dysregulated p63 expression that is observed in cancers and to define the biological contribution of the different domains of the p63 isotypes, ΔNp63α, ΔNp63p40, TAp63α, TAp63γ or β-galactosidase were overexpressed in primary murine keratinocytes. Microarray, RT–PCR and western blot analyses revealed that overexpression of ΔNp63p40, which lacks the entire α-tail present in ΔNp63α, permits expression of a full panel of differentiation markers. This is in contrast to overexpression of the full-length ΔNp63α, which blocks induction of keratin 10, loricrin and filaggrin. These findings support a role for the α-tail of ΔNp63α in blocking differentiation-specific gene expression. Overexpression of either TAp63 isotype permits keratin 10 and loricrin expression, thus the α-terminus requires the cooperation of the ΔN domain in blocking early differentiation. However, both TA isotypes block filaggrin induction. The ΔN-terminus is sufficient to maintain keratinocytes in a proliferative state, as both ΔN forms block Ca2+-mediated p21WAF1 induction and S-phase arrest, while sustaining elevated PCNA levels. No alteration in cell cycle regulation was observed in keratinocytes overexpressing TAp63α or TAp63γ. Clarifying the functional distinctions between p63 isotypes and domains will help to elucidate how their dysregulation impacts tumor biology and may suggest novel therapeutic strategies for modulating behavior of tumor cells with altered expression of p53 family members.

We performed rotational acetabular osteotomy in order to treat dysplasia of the hip in five ambulatory adults with cerebral palsy. There was one man and four women, with a mean age of 21 years (16 to 27) who were followed up for a mean of 12 years and two months.The mean Sharp angle improved from 52° to 43°, the mean acetabular index from 30.2° to 2.8°, the mean centre-edge angle from -5.6° to 29.2°, and the mean acetabular head index from 49.2 to 88.2. There was no progression of joint degeneration and relief from pain was maintained.Our results suggest that rotational acetabular osteotomy is a valuable option for the treatment of acetabular dysplasia in adults with cerebral palsy who have incapacitating pain in the hip.

To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C).

Treatment of tennis elbow is a problem. We performed magnetic resonance imaging (MRI) examinations of 11 elbows in 11 patients who were referred to us with refractory tennis elbow. Of the 11 elbows, 6 showed a high signal intensity focus on MRI T"2 images in the tendon of the extensor carpi radialis brevis at the lateral epicondyle. The other 5 elbows showed various abnormal findings on MRI. The mean age of the 6 patients with a high T"2 signal focus was 52.0 years, and the mean morbidity period was 25 months. We performed enucleation of the granulation focus through a surgical approach without detachment of the tendon origin of the extensor carpi radialis brevis. Pain was relieved and elbow function recovered in all 6 cases. This study demonstrates that MRI is an important decision-making tool in the surgical treatment of this condition. Enucleation of the granulation focus with high T"2 signal has proved to be effective in 6 selected cases.

OBJECTIVE: We aimed to determine the serum level of fibroblast growth factor-23 (FGF-23) in patients with primary hyperparathyroidism (pHPT) to understand its physiological role in the disorder. PATIENTS AND METHODS: Ninety-eight patients with pHPT who underwent parathyroidectomy formed the study group. We also measured serum FGF-23 in 11 of these patients on postoperative day 6. RESULTS: Serum FGF-23 levels was significantly higher in pHPT patients than in healthy controls (35.6+/-17.8 ng/l vs 28.9+/-11.2 ng/l (mean+/-s.d.); P<0.001 (Pearson's correlation coefficient)), but there was no significant difference in the serum FGF-23 level between pHPT patients with normal renal function (creatinine clearance (Ccr) of >or=70 ml/min) and healthy controls. Serum FGF-23 correlated positively with serum calcium (P<0.0001) and intact parathyroid hormone (PTH) (P<0.01), and negatively with Ccr (P<0.001), serum phosphate (P<0.05), and serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) (P<0.05). Multiple linear regression analysis of factors potentially determining serum FGF-23 levels in pHPT patients showed serum calcium (P<0.01) and Ccr (P<0.001) to be significant predictors. The serum levels of FGF-23 did not change after parathyroidectomy despite the normalization of serum calcium values. Multiple linear regression analysis revealed that serum FGF-23 was not a significant predictor of serum phosphate or 1,25(OH)(2)D in pHPT patients. CONCLUSIONS: FGF-23 may not play a significant role in regulating phosphate or 1,25(OH)(2)D in pHPT patients, especially in those with normal renal function. Further studies are warranted to determine the role of FGF-23 in renal insufficiency or failure.