On the structure of liver ribosomes

The morphology of liver ribosomes and their subparticles, large and small, has been investigated. Analysis of the images has been carried out by successive selection of models and by X-raying them under conditions simulating negative staining. The relation between the main views has been checked by tilting the specimens in an electron microscope through ± 30 °.The small subparticle consists of an elongated body, to one of the ends of which a short “head” is attached. A model has been proposed, whose projections on rotation with respect to the longitudinal axis would satisfy all observable types of images. According to the proposed model, the “head” is tilted with respect to the elongated portion. The length of the subparticle is 230 Å. The dimensions of the elongated portion in the transverse direction are 110 Å × 75 to 80 Å.The large subparticles in lateral view resemble short “rods” 220 to 240 Å long and about 70 to 95 Å wide. At a distance of about 60 Å from the left end of the particles a projection (60 Å in length) is seen, on the inner side of which a depression, or “channel”, filled with the contrasting substance is always observed. Next to this depression a second projection is located, whose height is about 30 Å. The channel is either a cavity in the body of the large subparticle or a part of the RNA without protein. The length of the channel is about 80 Å, the width is about 50 to 60 Å. The left end of the particles is characterized by two sharpened portions; as a result, a cavity that shows an obtuse angle profile makes its appearance. The opposite end of the particles is cut off at an angle of 45 °. In another view, the subparticles appear to be almost rectangular in shape; they are characterized by dimensions of 150 Å × 220 to 240 Å. It is likely that the large projection is displaced sideways with respect to the longitudinal axis of the particles. The asymmetry associated with this displacement gives rise to preferred arrangements of the subparticles on the supporting film. An analysis has been made of the most typical images of monomeric ribosomes, on the basis of which a suggestion is made about mutual orientation of subparticles in a monomer.     

Intérêt de la TEP/TDM au 18F-FDG dans la neurofibromatose de type 1, expérience du centre national de référence Henri-Mondor sur 10 ans

ObjectiveMalignant peripherals nerve sheath tumours (MPNST) are one of the leading causes of death in neurofibromatosis type 1 (NF1). Given the temporal and spatial multiplicity of suspicious lesions, the histological diagnosis of certainty might require iterative and decaying surgical procedure. Our objective was to determine the threshold values of metabolic metrics determined on ¹⁸F-FDG PET/CT (SUV_max, total lesion glycolysis [TLG], total metabolic tumour volume [TMTV], tumour-to-liver [T/L] ratio and heterogeneity index [HI]) in order to distinguish at best MPNST from benign lesion (simple neurofibromas [NF] or dysplastic NF).Patients and methodsHundred and seven patients from the national reference centre of NF1 Henri-Mondor, clinically suspects of TMGN, underwent 160 ¹⁸F-FDG PET/CT over a period of 10 years, between 2005 and 2015. The hypermetabolics lesions identified on ¹⁸F-FDG PET/CT were confronted with pathological analysis or clinico-radiological and metabolic follow-up of more than 6 months.ResultsFour hundred and eight hypermetabolics lesions were identified, of which 112 were histologically confronted with 38 simple NF, 29 dysplastic NF, 39 TMGN and 6 incidentalomas. The remaining 296 hypermetabolics lesions experienced a median follow-up of 40.4 months [13.5–137 months]. The optimal cut-off values for malignant lesions, determined by ROC curves, were in order of decreasing performance: T/L ratio > 2.03 (sensitivity 96%, specificity 88%); SUVmax > 4.74 (sensitivity 93%, specificity 86%); TLG > 172 (sensitivity 84%, specificity 76%); TMTV > 53.5 (sensitivity 83%, specificity 68%); HI > 1.63 (sensitivity 84%, specificity 54%).Conclusions¹⁸F-FDG PET/CT is a powerful diagnostic and prognostic tool in the management of TMGN. Metabolic metrics allow with good sensitivity and specificity to identify lesions transformed into TMGN. The advent of PET/MRI will undoubtedly allow in the near future to reinforce the diagnostic and prognostic performances for the detection of transformations of neurofibromas in TMGN.     

Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells

Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1–3/5–8) increased 3–13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6–4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy = 16% ± 3.6 vs. 5 Gy = 4.5% ± 0.3), 20 Gy increased it (21.4% ± 1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile.     

Automated recognition of malignancy mentions in biomedical literature

Background  

The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining.     

Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on chromosome 3p and in each case the LOH included the region to which the VHL gene has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC, haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest region of overlap was between D3S1038 and D3S18, a region that corresponds to the target region for the VHL gene from genetic linkage studies. The parental origin of the chromosome 3p25-p26 allele loss could be determined in seven tumours from seven familial cases; in each tumour, the allele lost had been inherited from the unaffected parent. Our results suggest that the VHL disease gene functions as a recessive tumour suppressor gene and that inactivation of both alleles of the VHL gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL gene mutations may be required but may not be sufficient for tumourigenesis in VHL disease.     

Properties of reticulum cell sarcomas in SJL/J mice: II. Fate of labeled tumor cells in normal and irradiated syngeneic mice

Transplantable reticulum cell sarcoma (RCS) cells were labeled with ³H-uridine or ³H-thymidine in vitro and injected intravenously into normal and irradiated syngeneic SJL/J mice. RCS cells exhibited typical B cell migration characteristics in peripheral lymphoid organs in both normal and irradiated recipients, localizing in follicles in a pattern resembling that of labeled normal bone marrow cells. However, over the first 72 hr after transfer, RCS cells diluted their label much less in irradiated than in normal recipients, reflecting their inability to proliferate in the irradiated hosts. The presence of unlabeled tumor cells did not significantly affect the distribution of labeled normal bone marrow or lymph node cells in the recipients. Thus, RCS fails to grow in irradiated recipients in spite of undisturbed homing characteristics and in the absence of any evidence of cytotoxic influences from the host.