Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors

Adhesive interactions with the extracellular matrix of the bone marrow (BM) stroma are of critical importance in the regulation of hematopoiesis. In part, these interactions are presumed to play an important role in retaining CD34+ hematopoietic progenitor cells (HPCs) within the BM environment, in close proximity with BM stromal cells and the cytokines they produce. Evidence of a more direct role for cell adhesion in the regulation of hematopoiesis is provided by recent data showing that adhesive interactions can also provide important costimulatory signals. We have previously shown that normal CD34+ HPCs express high levels of fibronectin (Fn) receptors very late antigen-4 (VLA-4) and VLA-5 in a low-affinity state, which do not allow HPCs to strongly adhere on immobilized Fn, and that cytokines such as interleukin-3, granulocyte-monocyte colony-stimulating factor, and stem cell factor transiently activate these receptors, providing HPCs with an adhesive phenotype on Fn. Thus, knowledge of the functional states of adhesion receptors is critical to our understanding of the physiological mechanisms responsible for the regulation of normal hematopoiesis. Herein, we show that combinations of cytokines that synergize to stimulate the proliferation of CD34+ HPCs result in additive stimulation of the adhesion of these cells to Fn. Thus, the activation level of Fn receptors expressed by normal CD34+ HPCs is highly correlated with their proliferative state, suggesting a functional link between these two events. Therefore, we propose a 2- step model with an initial activation of VLA-4 and VLA-5 generated by cytokine receptors that is followed by a secondary signal resulting from Fn binding to VLA-4 and VLA-5, which may cooperate with those generated by cytokine receptors.     

Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings

Computed tomography (CT) was compared with chest radiography in the assessment of disease severity in 27 patients with sarcoidosis. The CT scans and radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by visual scoring (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification. The severity of parenchymal changes on the CT scan and on the radiograph was significantly correlated with the severity of dyspnea (r = .61 and .58, respectively; P less than .001), diffusing capacity (r = -.62 and -.52, P less than .01), and vital capacity (r = -.49 and -.51, P less than .01). Patients with predominantly irregular opacities had more severe dyspnea and lower lung volumes than patients with predominantly nodular opacities (P less than .05). The authors conclude that in patients with sarcoidosis, the radiographic and CT assessments of disease severity show similar correlation with clinical and functional impairment.     

A model for estimating incremental benefits and costs of testing donated blood for human immunodeficiency virus antigen (HIV-Ag)

We propose a model for estimating the benefit of adding a test for the human immunodeficiency virus antigen (HIV-Ag) to current procedures for testing donated blood. Using this model, data on HIV infection from published studies, and certain assumptions about blood donor behavior, we estimate that the probability of detecting an additional HIV-infective blood component is approximately 1 in 4,860,000. If this estimate is correct, adding HIV-Ag testing would prevent approximately 4 cases of primary transfusion-transmitted HIV infection annually in the United States. After adjustments for the median incubation period for AIDS, and for mortality due to primary illnesses, this estimate represents prevention of approximately 1 case of AIDS per year, within the 4 years after transfusion. A primary advantage of this model is its adaptability for recalculating cost-benefit analyses if more sensitive tests for HIV infection become available. In addition, we propose that comparing the anticipated costs and benefits of HIV-Ag testing to other possible uses of these funds should be an important factor in assessing the desirability of HIV-Ag testing.     

Low tuberculosis notification in mountainous Vietnam is not due to low case detection: a cross-sectional survey

Background  

Studies show that tuberculosis notification declines with increasing altitude. This can be due to declining incidence or declining case detection. In Vietnam notification rates of new smear-positive tuberculosis in the central mountainous provinces (26/100,000 population) are considerably lower than in Vietnam in general (69/100,000 population). In order to clarify whether this is explained by low incidence or low case detection, we aimed to assess the prevalence of new smear-positive tuberculosis among adults with prolonged cough in three mountainous provinces in central Vietnam.     

Synthesis of coagulation factor V by cultured aortic endothelium

Bovine aortic endothelium has been examined with respect to the synthesis of coagulation factor V. After cultured cells reached confluency, samples of supernatant culture media and solubilized cells were analyzed for factor V in a two-stage bioassay and in a double- antibody radioimmunoassay. In addition, preconfluent cells were pulsed for 4 days with 35S-methionine in methionine-free media. After the 4- day pulse, supernatant media were chromatographed on a factor V monoclonal antibody-Sepharose resin to isolate 35S-labeled factor V. The isolated material and 125I-factor V standards were analyzed by electrophoresis and autoradiography. The bioassay indicated an increase, with time, of unactivated factor V in the culture supernatant, whereas solubilized cells were negative for factor V. The radioimmunoassay indicated an increase, with time, of factor V antigen in the culture supernatants, and the solubilized cells yielded a constant level of antigen per cell. Autoradiograms of electrophoretograms of immunoadsorbed 35S-culture supernatant with 125I- factor V/Va standards revealed labeled proteins with electrophoretic mobilities compatible with 125I-factor V/Va standards. The data obtained from three different sources-bioassay, radioimmunoassay, and 35S-methionine incorporation-all indicate that factor V is synthesized by cultured bovine aortic endothelium.     

Glomerulus Detection Using Segmentation Neural Networks

Journal of Digital Imaging - Digital pathology is vital for the correct diagnosis of kidney before transplantation or kidney disease identification. One of the key challenges in kidney diagnosis is...     

SHARING THE CARE: A project to enable prostate cancer care to be delivered in the community

Prostate cancer has become the 2nd most common cancer in men worldwide. An ageing population and treatment improvements are increasing the number of men living with and beyond cancer. In 2013, there was both scant evidence to guide as to when, where or how men with prostate cancer should be followed up and neither, it appears, pointing to agreed pathways. Generally, follow up regimes are based on tradition and expert medical opinion rather than research or patient need. For men to have their follow up with their GP, several factors need to be in place such as a single system, an improved exchange of experiences, as well as information and knowledge sharing. A recent presentation of a randomized control trial has shown that there are no differences between secondary and primary care follow up. Understanding that the current model of follow up was not working and was unsustainable, a review of urological services was undertaken in 2011 in a large National Health Service (NHS) district general hospital in the north of England. The review evaluated current services, noting that some follow up pathways did not necessarily need to be undertaken within a secondary are setting. The process of relocating patients for primary care review, involved creating a shared care process for prostate cancer. A workstream consisting of consultant urologists, nurse specialists, GPs, service managers and clinical commissioners was convened. Protocols containing specific responsibilities for secondary and primary care were devised. The review and workstream, included a shared vision for improving and sustaining services. Whilst safely moving follow up from secondary to primary care, benefits were realized such as care closer to the home. In conclusion a radical approach to follow up was needed and undertaken. Shared care has yielded success for the patient, primary and secondary care.     

Integrating next‐generation sequencing into the diagnostic testing of inherited cancer predisposition

The clinical application of next‐generation sequencing (NGS) as a diagnostic tool has become increasingly evident. The coupling of NGS technologies with new genomic sequence enrichment methods has made the sequencing of panels of target genes technically feasible, at the same time as making such an approach cost‐effective for diagnostic applications. In this article, we discuss recent studies that have applied NGS in the diagnostic setting in relation to hereditary cancer.