Multimodality imaging of direct ureteric involvement in non-Hodgkin's lymphoma using PET/CT, CT urography and antegrade CT pyelography

Positron emission tomography/computed tomography (PET/CT), CT urography (CTU) and antegrade CT pyelography (ACTP) findings of ureteric involvement in non-Hodgkin's lymphoma (NHL) are presented. PET/CT performed for restaging in a patient with a 2-year history of Stage 4 NHL showed increased 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) activity in a distended ureteric segment. CTU and ACTP, performed to further evaluate PET/CT findings, demonstrated diffuse, irregular and concentric thickening of the affected ureteric walls, accompanied by severe irregular narrowing of affected ureteric lumen. Tissue sampling using percutaneous CT-guided biopsy revealed NHL involvement of the ureter. To the best of our knowledge, this is the first report of PET/CT, CTU and ACTP findings of ureteric NHL.     

Ovarian tissue cryopreservation in hematologic malignancy: ten years' experience

Cryopreservation of ovarian tissue is currently practiced in an attempt to preserve fertility before commencing potentially sterilizing chemotherapy. Clinical and laboratory guidelines are needed to standardize the procedure. Over the last 10 years ovarian tissue was stored in female patients with hematologic malignancies. Patients' records and consultation charts were evaluated, surgical and laboratory reports were revised and ovarian histology was investigated. Fifty-six patients with hematologic malignancies (age 24 ± 5.5) had cryopreserved ovarian tissue. Thirty-three patients had Hodgkin's disease, 14 non-Hodgkin's lymphoma, 6 acute leukemia, and 3 chronic myelocytic leukemia. Harvesting of ovarian tissue was also performed following previous exposure to chemotherapy (33 patients), 13 of them shortly after the chemotherapy. Partial oophorectomy was the preferred surgical procedure. Fertility was restored with ovarian tissue transplantation in a sterilized patient and following fertility treatment in a patient with very low ovarian reserve. We recommend that indications and timing of ovarian tissue banking should be individualized. Patients previously exposed to chemotherapy can consider ovarian tissue freezing. The extent of tissue removed should take into account the large number of follicles lost and the risk of future sterilization. Tissue handling should enable further investigation of primordial follicles and identification of cancer cells.     

Four-factor prothrombin complex concentrate use for on-label versus off-label indications: a retrospective cohort study

Journal of Thrombosis and Thrombolysis - This study aimed to characterize the utilization of four-factor prothrombin complex concentrate (4F-PCC) at a tertiary academic medical center and evaluate...     

Endophthalmitis panorama in the Jerusalem area

International Ophthalmology - The spectrum of microbial infections and the pattern of their susceptibility are variable among communities. Researching these data will lead to the establishment of...     

A novel transgenic mouse expressing double mutant tau driven by its natural promoter exhibits tauopathy characteristics

The neurofibrillary-tangles (NTFs), characteristic of tauopathies including Alzheimer's-disease (AD), are the pathological features which correlate best with dementia. The objective of our study was to generate an authentic transgenic (tg) animal model for NFT pathology in tauopathy/AD. Previous NFT-tg mice were driven by non-related/non-homologous promoters. Our strategy was to use the natural tau promoter for expressing the human-tau (htau) gene with two mutations K257T/P301S (double mutant, DM) associated with severe phenotypes of frontotemporal-dementia in humans. Cellular, biochemical, behavioral and electrophysiological studies were subsequently conducted. The tg mice showed a tolerated physiological level of the DM-htau protein, mostly in cortex and hippocampus. The mice demonstrated tauopathy-like characteristics, which increased with age, that included NFT-related pathology, astrogliosis, argyrophilic plaque-like (amyloid-free) structures in brain, with memory deficits and signs of anxiety. Moreover, the tg mice showed a robust synaptic plasticity deficit selectively expressed in a severe impairment in their ability to maintain hippocampal long-term-potentiation (LTP) in response to stimulation of the perforant path, providing evidence that “tau-pathology only” is sufficient to cause this memory and learning-associated deficit. This is a unique mutant-htau-tg model which presents a wide spectrum of features characteristic of tauopathy/AD, which does not show unrelated motor deficits described in other models of tauopathy. In addition, expressing the DM-htau in a neuronal cell model resulted in tau-aggregation, as well as impaired microtubule arrangement. Both animal and cell models, which were regulated under the natural tau promoter (of rat origin), provide authentic and reliable models for tauopathy, and offer valuable tools for understanding the molecular events underlying tauopathies including AD.     

Astrocytes facilitate melanoma brain metastasis via secretion of IL‐23

Melanoma is the leading cause of skin cancer mortality. The major cause of melanoma mortality is metastasis to distant organs, frequently to the brain. The microenvironment plays a critical role in tumourigenesis and metastasis. In order to treat or prevent metastasis, the interactions of disseminated tumour cells with the microenvironment at the metastatic organ have to be elucidated. However, the role of brain stromal cells in facilitating metastatic growth is poorly understood. Astrocytes are glial cells that function in repair and scarring of the brain following injury, in part via mediating neuroinflammation, but the role of astrocytes in melanoma brain metastasis is largely unresolved. Here we show that astrocytes can be reprogrammed by human brain‐metastasizing melanoma cells to express pro‐inflammatory factors, including the cytokine IL‐23, which was highly expressed by metastases‐associated astrocytes in vivo. Moreover, we show that the interactions between astrocytes and melanoma cells are reciprocal: paracrine signalling from astrocytes up‐regulates the secretion of the matrix metalloproteinase MMP2 and enhances the invasiveness of brain‐metastasizing melanoma cells. IL‐23 was sufficient to increase melanoma cell invasion, and neutralizing antibodies to IL‐23 could block this enhanced migration, implying a functional role for astrocyte‐derived IL‐23 in facilitating the progression of melanoma brain metastasis. Knocking down the expression of MMP2 in melanoma cells resulted in inhibition of IL‐23‐induced invasiveness. Thus, our study demonstrates that bidirectional signalling between melanoma cells and astrocytes results in the formation of a pro‐inflammatory milieu in the brain, and in functional enhancement of the metastatic potential of disseminated melanoma cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The role of the heterochronic microRNA let-7 in the progression of aging

Aging results in reduced tissue homeostasis and declined ability to replace damaged cells by new functional ones. In many tissues, homeostasis and repair are supported by tissue-specific stem cells that induce to generate differentiated cells in accordance with physiological requirements. Heterochronic genes, initially described in worms, specify the timing of fate decisions in each cell type and thus ensure a synchronized program of development throughout the animal. The heterochronic let-7 microRNA plays an important role in development by repressing cell fate regulators to promote stage progression. Recent studies reveal a new role of let-7 which occurs much later in life and regulates aging of several tissues, across species. In this article I review the current knowledge on the fate mechanisms of tissue stem cells during aging that are modulate by let-7, as well as its co-partners and its target genes. I also discuss the therapeutic potential of controlling heterochronic events as a possible treatment for aging‐related disorders. Timing is a clear dimension of organisms' development that may be difficult to witness in aging stages that are not as defined as in embryonic development. Exploring the regulation of stem cell aging by let-7 may ultimately reveal novel timing mechanisms.