Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository

The National Institutes of Health have placed significant emphasis on sharing of research data to support secondary research. Investigators have been encouraged to publish their clinical and imaging data as part of fulfilling their grant obligations. Realizing it was not sufficient to merely ask investigators to publish their collection of imaging and clinical data, the National Cancer Institute (NCI) created the open source National Biomedical Image Archive software package as a mechanism for centralized hosting of cancer related imaging. NCI has contracted with Washington University in Saint Louis to create The Cancer Imaging Archive (TCIA)—an open-source, open-access information resource to support research, development, and educational initiatives utilizing advanced medical imaging of cancer. In its first year of operation, TCIA accumulated 23 collections (3.3 million images). Operating and maintaining a high-availability image archive is a complex challenge involving varied archive-specific resources and driven by the needs of both image submitters and image consumers. Quality archives of any type (traditional library, PubMed, refereed journals) require management and customer service. This paper describes the management tasks and user support model for TCIA.     

Objectively characterizing Huntington’s disease using a novel upper limb dexterity test

Journal of Neurology - The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent...     

Enrichment of prostate cancer cells from blood cells with a hybrid dielectrophoresis and immunocapture microfluidic system

The isolation of circulating tumor cells (CTCs) from cancer patient blood is a technical challenge that is often addressed by microfluidic approaches. Two of the most prominent techniques for rare cancer cell separation, immunocapture and dielectrophoresis (DEP), are currently limited by a performance tradeoff between high efficiency and high purity. The development of a platform capable of these two performance criteria can potentially be facilitated by incorporating both DEP and immunocapture. We present a hybrid DEP-immunocapture system to characterize how DEP controls the shear-dependent capture of a prostate cancer cell line, LNCaP, and the nonspecific adhesion of peripheral blood mononuclear cells (PBMCs). Characterization of cell adhesion with and without DEP effects was performed in a Hele-Shaw flow cell that was functionalized with the prostate-specific monoclonal antibody, J591. In this model system designed to make nonspecific PBMC adhesion readily apparent, we demonstrate LNCaP enrichment from PBMCs by precisely tuning the applied AC electric field frequency to enhance immunocapture of LNCaPs and reduce nonspecific adhesion of PBMCs with positive and negative DEP, respectively. Our work shows that DEP and immunocapture techniques can work synergistically to improve cancer cell capture performance, and it informs the design of future hybrid DEP-immunocapture systems with improved CTC capture performance to facilitate research on cancer metastasis and drug therapies.     

Culture of primary rat hippocampal neurons: design, analysis, and optimization of a microfluidic device for cell seeding, coherent growth, and solute delivery

We present the design, analysis, construction, and culture results of a microfluidic device for the segregation and chemical stimulation of primary rat hippocampal neurons. Our device is designed to achieve spatio-temporal solute delivery to discrete sections of neurons with mitigated mechanical stress. We implement a geometric guidance technique to direct axonal processes of the neurons into specific areas of the device to achieve solute segregation along routed cells. Using physicochemical modeling, we predict flows, concentration profiles, and mechanical stresses within pertiment sections of the device. We demonstrate cell viability and growth within the closed device over a period of 11 days. Additionally, our modeling methodology may be generalized and applied to other device geometries.     

A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non‐specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post‐treatment symptoms.