Background and purpose
The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been ...only partially elucidated.
Methods
Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data.
Results
In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18–78 years), the mean age at death was 53 years (range 23–84 years) and the mean disease duration was 6.8 years (range 1–29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158–11.177). There was an age‐dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion‐restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy‐nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype−genotype correlations.
Conclusions
The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.
Background and purpose
To establish and validate diagnostic criteria for adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony‐stimulating factor 1 receptor ...(CSF1R) mutation.
Methods
We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide ‘probable’ and ‘possible’ designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation‐negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations.
Results
Among the CSF1R mutation‐positive cases, 50 cases (60%) were diagnosed as ‘probable’ and 32 (39%) were diagnosed as ‘possible,’ leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled ‘probable’ or ‘possible’ to the total number of cases. With regard to specificity, 22 cases (42%) with mutation‐negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria.
Conclusions
These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.
Abstract The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human ...placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat to the forefront in placentation research.
We report here on the early stage of the precipitation behavior of aged Al–Li–Cu alloys using transmission electron microscopy. The δ′ phase (Al
3Li, L1
2 structure (Structurbericht)) was found to ...exist in the as-quenched specimen containing 2.4 wt%-Li, whereas no precipitation was observed in the as-quenched specimen with 1.6 wt%-Li. After aging at 100 °C for 3 h, GP-I zones nucleated homogeneously in both specimens; but no δ′ phase was detected in the 1.6 wt%-Li alloy at that stage. As the aging proceeds, the δ′ phase nucleates and grows on the GP-I zones. The composite structure, in which the GP-I zone is flanked by a pair of lenticular δ′ particles, is stable in 180–200 °C. The facing lenticular δ′ particles on a GP-I zone were systematically found to be anti-phase with respect to each other.
The Diels–Alder reaction of trifluorovinyl substances with various dienes proceeded well to give the corresponding trifluorinated cyclohexene derivatives in a regiospecific manner, while ...2,3-difluorobuta-1,3-diene molecules also underwent a smooth Diels–Alder reaction with various dienophiles to afford the corresponding vic -difluorocyclohexene structure.
The atomic structure of CoPt and FePt nanoparticles (with a diameter between 2 and 5 nm) has been studied by transmission electron microscopy. The particles have been produced by a laser vaporization ...cluster source and annealed under vacuum in order to promote chemical ordering. For both alloys, we observe a coexistence of crystalline and multiply twinned particles with decahedral or icosahedral shapes. In addition to particles corresponding to a single L1(0) ordered domain, we put into evidence that even small particles can display several L1(0) domains. In particular, the chemical order can be preserved across twin boundaries which can give rise to spectacular chemically ordered decahedral particles made of five L1(0) domains. The stability of such structures, which had been recently predicted from theoretical simulations, is thus unambiguously experimentally confirmed.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate ...diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.
Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor ...that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC
value of PLC/PRF/5 cells from 13.0±0.8 μM in normoxia to 21.3±1.1 μM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore,
analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.
We herein report a significant improvement of the ductility of AZ31 (Al: 3
wt%, Zn: 1
wt%, balance Mg) sheets processed by differential speed rolling (DSR). The DSR sheets under tension in the ...rolling direction exhibited a plastic strain more than 1.5 times larger than the sheets prepared by conventional rolling (CR), and simultaneous improvements of in-plane isotropy. The origin of these changes has been examined by texture and structural characterizations. The (0
0
0
2) pole intensity of the as-rolled DSR sheet is strongly accumulated in the normal direction, which is preserved after deformation regardless of tensile directions; while that of as-rolled CR sheet show clear splitting, which further broadens after tensile tests. It is suggested that these changes are brought about by the application of a large shear strain to DSR sheets, which resulted in the clear (0
0
0
2) texture, and subsequent ease of the activation of prismatic slip during the deformation.
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