Beaumont health system biobank: a multidisciplinary biorepository and translational research facility.

The Beaumont BioBank model is a multidisciplinary facility that is designed to provide access and opportunity for research-minded clinicians to become involved in research without the need for their own research infrastructure, thus increasing the research effort across the Health System. We describe a biobank model that works primarily in operating rooms for tissue collection and utilizes a generic consent process to facilitate rapid and accurate collection of biospecimens. The model combines both a biorepository that collects specimens based on clinical questions and also a translational research facility that undertakes biomarker-based research on those specimens in a seamless and efficient process.

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by L-Deprenyl.

Background: Development of mammary tumors is an age-associated phenomenon that is likely due to deficits in the neuroendocrine-immune interactions. Previously, we demonstrated that L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, can enhance immune responses and restore noradrenergic (NA) innervation in the spleens of rats with carcinogen-induced and spontaneously developing mammary tumors.

Objectives: To investigate whether (1) treatment of early middle-aged female rats would prevent the spontaneous development of mammary tumors accompanied by restoration of immunity in the spleen and draining lymph nodes (DLN) and sympathetic NA innervation in the spleen and (2) deprenyl can influence the proliferation of estrogen receptor (ER)-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231 and Hs 578T) human breast cancer cells.

L-Deprenyl reverses age-associated decline in splenic norepinephrine, interleukin-2 and interferon-γ production in old female F344 rats.

Unlabelled: Aging in female rats is associated with cessation of reproductive cycles, development of mammary cancer, and increased incidence of autoimmune diseases. Previously, we demonstrated an age-related decline in sympathetic noradrenergic (NA) innervation in the spleen and lymph nodes of female F344 rats accompanied by significantly reduced natural killer cell activity, interleukin (IL)-2 and interferon (IFN)-γ production, and T- and B-cell proliferation, suggesting possible links between sympathetic activity and immunosenescence.

Objectives: The aim of this study is to investigate the effects of L-(-)-deprenyl, a monoamine oxidase-B inhibitor, on the sympathetic nervous system and cell-mediated immune responses in old female rats.

Increasing accrual in cancer clinical trials with a focus on minority enrollment: The William Beaumont Hospital Community Clinical Oncology Program Experience.

Background: The authors reviewed changes in accrual to cancer clinical trials over the last 2 decades at their institution with a focus on minority participation after the implementation of a community clinical oncology program (CCOP) and an aggressive, education-orientated minority outreach program (MOP).

Methods: Data on patient enrollment in clinical trials for the years 1988 to 2010 was obtained from the William Beaumont Hospital (WBH) Cancer Clinical Trials Office. The type and number of cancers diagnosed and treated during the same period were obtained from the WBH tumor registry data.

Age-associated alterations in sympathetic noradrenergic innervation of primary and secondary lymphoid organs in female Fischer 344 rats.

Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation.

Age effects on macrophage function vary by tissue site, nature of stimulant, and exercise behavior.

We explored the effects of aging on macrophage function in male BALB/c mice from three age groups: young (2 months), middle-aged (12 months), and old (21 months). Macrophages were collected from alveoli, peritonea, and spleens of each age group. Cells were cultured in vitro with LPS or LPS+IFN-gamma and assayed for production of IL-1, IL-12, NO, and TNF-alpha.

Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats.

In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography.

Sympathetic nerve destruction in spleen in murine AIDS.

In susceptible strains of mice, the LP-BM5 mixture of murine retroviruses induces the fatal immunodeficiency disease known as murine acquired immunodeficiency syndrome (murine AIDS or MAIDS). We have previously reported that murine AIDS produces a profound depletion of splenic norepinephrine (NE). Here, we demonstrate that NE depletion is limited to the spleen, a major site affected by LP-BM5 infection.

Modulation of neuroendocrine--immune signaling by L-deprenyl and L-desmethyldeprenyl in aging and mammary cancer.

The aging process is characterized by a decline in cellular functions of diverse systems of the body, including the neuroendocrine-immune network. One neuroendocrinological theory of aging is based on findings that the loss of hypothalamic neurotransmitter functions and an imbalance in hormonal secretion contribute to the cessation of reproductive cycles and the development of mammary and pituitary tumors. One potential cause of immunosenescence is an age-related decline in the regulatory functions of sympathetic noradrenergic nerve fibers whose neurotransmitters signal lymphoid cells in the bone marrow, thymus, spleen, and lymph nodes.

Age-related changes in noradrenergic sympathetic innervation of the rat spleen is strain dependent.

Previous findings from our laboratory revealed an age-related decline in noradrenergic (NA) sympathetic innervation of the spleen in male Fischer 344 (F344) rats. The purpose of this study was to determine whether other rat strains also progressively lose NA sympathetic nerves in the aging spleen. Sympathetic innervation of spleens from 3- and 21-month-old male F344, Brown Norway (BN), BN X F344 (BNF(1)), and Lewis rats was examined using fluorescence histochemistry to localize catecholamines combined with morphometric analysis and using high-performance liquid chromatography with electrochemical detection for measuring norepinephrine (NE).

Chemical sympathectomy has no effect on the severity of murine AIDS: murine AIDS alone depletes norepinephrine levels in infected spleen.

Numerous studies have shown that alterations in sympathetic nervous system (SNS) function produced by beta-adrenergic receptor blockade or chemical sympathectomy can produce changes in T and B lymphocyte function and both innate and acquired immune responses. However, fewer studies have investigated changes in immune response following SNS alterations in animal models of disease. We tested whether blocking SNS activity using 6-OHDA or the beta-receptor antagonist nadolol alters the typical pattern in production of T helper 1 (Th1) and Th2 cytokines seen in cultures of spleen cells from C57BL/6 mice infected with murine AIDS (MAIDS).