AS RECENTLY as 1900, tuberculosis, influenza, and pneumonia were the leading causes of death in our country (1). For the most part, however, these infectious diseases, as well as those of poor hygiene or undernutrition, no longer plague us. Instead, we succumb most frequently to heart disease and cancer, diseases of slow degeneration (1). Most of all, unlike so many in the generations before us, we are in a position to age. Regardless of what else occurs, we age, we become more constrained by the discrepancy between what we were and what we have become, and each step becomes harder. The goal in the study of aging is not to halt the process, because we can no more be cured of aging than of birth. The goal, instead, is to slow and soften the sharpest edges of the biological unraveling that constitutes aging. Over the past 5 yr, we have examined some of the sharpest edges of the pathology of aging. We have studied the capacity of aged organisms to respond appropriately to stress and the capacity of stress to...

The Neuroendocrinology of Stress and Aging: The Glucocorticoid Cascade Hypothesis*

Over the past 5 yr, we have examined some of the sharpest edges of the pathology of aging. We have studied the capacity of aged organisms to respond appropriately to stress and the capacity of stre...

The Neuroendocrinology of Stress and Aging: The Glucocorticoid Cascade Hypothesis

1. This paper reviews recent findings on cellular and humoral immunity and inflammatory markers in depression. 2. It is shown that major depression may be accompanied by systemic immune activation or an inflammatory response with involvement of phagocytic (monocytes, neutrophils) cells, T cell activation, B cell proliferation, an "acute" phase response with increased plasma levels of positive and decreased levels of negative acute phase proteins, higher autoantibody (antinuclear, antiphospholipid) titers, increased prostaglandin secretion, disorders in exopeptidase enzymes, such as dipeptidyl peptidase IV, and increased production of interleukin (IL)-1 beta and IL-6 by peripheral blood mononuclear cells. 3. It is hypothesized that increased monocytic production of interleukins (Il-1 beta and Il-6) in severe depression may constitute key phenomena underlying the various aspects of the immune and "acute" phase response, while contributing to hypothalamic-pituitary-adrenal-axis hyperactivity, disorders in serotonin metabolism, and to the vegetative symptoms (i.e. the sickness behavior) of severe depression.

Evidence for an immune response in major depression: a review and hypothesis

Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

/pdf/the-influence-of-bio-behavioural-factors-on-tumour-biology-144zmhhl5z.pdf

The influence of bio-behavioural factors on tumour biology: pathways and mechanisms

The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions.

Emotional, psychosocial, or anxiety-stimulated stress produces increased plasma concentrations of adrenal corticoids and other hormones though well-known neuroendocrine pathways. A direct consequence of these increased corticoid concentrations is injury to elements of the immunological apparatus, which may leve the subject vulnerable to the action of latent oncogenic viruses, newly transformed cancer cells, or other incipient pathological processes that are normally held in check by an intact immunological apparatus. This article describes studies that examine the adverse effects of increased plasma concentrations of adrenal corticoids on the thymus and thymus-dependent T cells, inasmuch as these elements constitute a major defense system against various neoplastic processes and other pathologies. The studies demonstrate that anxiety-stress can be quantitatively induced and the consequences measured through specific biochemical and cellular parameters, providing that authentic quiescent baselines of these conditions are obtained in the experimental animals by the use of low-stress protective housing and handling techniques.

http://science.sciencemag.org/content/sci/212/4499/1100.full.pdf

Psychoneuroendocrine influences on immunocompetence and neoplasia

Application of Chromatography to the Separation of Subcellular, Enzymatically Active Granules

Application of Chromatography to Segregation Studies of the Agent of Chicken Tumor I (Rous Sarcoma Virus).

SummaryAsparaginase, injected in conventional therapeutic doses into mice previously inoculated with the lactate dehydrogenase-elevating virus (LDH-virus), disappeared from the peripheral blood at a significantly slower rate than in corresponding virus-free mice. Direct testing of the transplanted tumors and leukemias employed in the earlier studies on the antitumor properties of asparaginase have indicated that the virus, was unknowingly present. The evidence indicates that the virus, through its impairment of host enzyme clearance and possibly other factors, played a significant role in the observed therapeutic effects of EC-2 l-asparaginase against sensitive mouse leukemia and lymphosarcoma.We thank J. D. Loveless, M. A. Fitzmaurice, and Edith R. Shapiro for assistance.

Asparaginase clearance: influence of the LDH-elevating virus.

SummaryFollowing infection of intact mice with the LDH-virus, a significant thymus involution was observed. Since there was no thymus involution in adrenalectomized mice infected with the virus, a virus-induced adrenal cortical hormone increase or activation is postulated. The observation of an increase in spleen and lymph node weight in both intact and adrenalectomized LDH-virus infected mice may result from a virus-induced proliferation of thymus-independent lymphatic tissue, which is unaffected by the adrenal cortical hormones.

Vernon Riley

Papers

Psychoneuroendocrine influences on immunocompetence and neoplasia

Application of Chromatography to the Separation of Subcellular, Enzymatically Active Granules

Application of Chromatography to Segregation Studies of the Agent of Chicken Tumor I (Rous Sarcoma Virus).

Asparaginase clearance: influence of the LDH-elevating virus.

Thymolytic and adrenal cortical responses to the LDH-elevating virus.