How does anxiety sensitivity increase risk of chronic medical conditions?

Anxiety sensitivity (AS; fear of anxiety‐related symptoms) is an established transdiagnostic risk factor for psychiatric disorders and is related to a variety of chronic medical conditions. However, AS has not been established as a risk factor for chronic medical conditions. In this study, we review studies on AS and chronic medical conditions (and symptoms/behaviors related to chronic medical conditions) and propose four pathways through which AS may increase risk of chronic medical conditions: (a) increasing fear of medical condition‐specific symptoms, (b) perpetuating avoidance of healthy activities, (c) promoting engagement in unhealthy behaviors, and (d) increasing risk of detrimental pathophysiological and pathomechanical alterations. We also discuss the potential utility of using AS reduction interventions as a means of reducing risk of chronic medical conditions.     

How does antigen retrieval work?

The introduction of antigen retrieval has enabled immunohistology to become an integral component of morphologic diagnosis, routinely employed in cancer diagnosis, and for the identification of therapeutic and prognostic markers. The mechanism of antigen retrieval, however, remains speculative with the key to our understanding embedded in the actions of formaldehyde on proteins. One commonly held concept is that heat primarily breaks down protein cross-linkages that occur with aldehyde fixation, thus "unmasking" protein epitopes of interest. Enzymatic pretreatment is also thought to have a similar action whereas such "breakages" are the result of extremely rapid molecular movement induced by microwaves and ultrasound. The formation of rigid cagelike calcium complexes during formaldehyde fixation is another suggested mechanism of antigen masking requiring chelating agents for reversal. A more recent suggestion for the antigen retrieval phenomenon has evoked the Mannich reaction, which occurs with the cross-linking of some proteins. Such cross-linkages can be hydrolyzed by heat or alkalis so that the process of antigen retrieval may be the simple removal of such cross-linked proteins that are sterically interfering with the binding of antibodies to linear protein epitopes in the tissue section. We are clearly not yet in possession of all the answers to the problem.     

How does exercise cause asthma attacks?

PURPOSE OF REVIEW: To remind readers that evaporative water loss from the airway surface is the stimulus for exercise-induced bronchoconstriction. To emphasize that recruitment of the peripheral airways determines severity of exercise-induced bronchoconstriction. To draw attention to the potential for injury of the epithelium and for plasma exudation to contribute to the pathogenesis of exercise-induced bronchoconstriction in athletes. To emphasize that many inflammatory mediators are involved in exercise-induced bronchoconstriction and that some are found in both asthmatic and healthy subjects. RECENT FINDINGS: That inflammatory mediators are released into the airways in response to exercise and can be measured by inducing sputum (histamine, cysteinyl leukotrienes) or collecting condensate from exhaled air (cysteinyl leukotrienes and adenosine). The concentration of mediators was reduced in response to a combination of loratadine and montelukast. Exercise is a stimulus for upregulating the genes coding for the 5-lipoxygenase pathway in healthy subjects. SUMMARY: Dehydration of the airways results in release of mediators. The likely source of these mediators is the mast cell. Epithelial injury occurs in exercise-induced bronchoconstriction. The process of repair may contribute to the development of airway hyperresponsiveness in healthy subjects. Measuring the airway response to exercise, or a surrogate for exercise, as an indicator of airway hyperresponsiveness is warranted in patients with symptoms of asthma.     

How does the brain control lifespan?

There is generally a positive correlation between brain/body size ratio and lifespan, particularly among mammals, suggesting a role for the brain in determining lifespan. Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that, indeed the brain may control lifespan. Signaling pathways involved in both central nervous system and peripheral stress responses and regulation of energy metabolism may play important roles in lifespan determination. Indeed, genetic and environmental manipulations of these systems can greatly affect lifespan by changing levels of hormones that modulate energy metabolism, stress resistance and regenerative capacity of cells throughout the body. A signal transduction pathway in neurons involving receptors coupled to phosphatidylinositol-3-kinase, Akt and glycogen synthase kinase-3beta appears to play a key role in regulation of longevity by the brain. Mutations in genes that encode proteins in the insulin signaling pathway can increase lifespan in C. elegans and Drosophila, this signaling pathway in neurons in the brain may be particularly important in limiting lifespan. Dietary restriction results in the upregulation of brain-derived neurotrophic factor (BDNF) in the brain, which may increase the resistance of neurons to aging. Interestingly, BDNF signaling in the brain can increase peripheral insulin sensitivity, suggesting a mechanism whereby the brain can control lifespan. We speculate that during evolution the brain took on the task of monitoring and controlling peripheral energy metabolism, and thereby regulating lifespan in the context of food availability. Roles for other evolutionarily conserved brain signaling pathways in lifespan determination are likely to be discovered in the near future.     

Why does diabetes mellitus increase the risk of cardiovascular disease?

The main etiology for mortality and a great percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The pathogenesis of cardiovascular disease (CVD) in diabetes is multifactorial and can be affected by metabolic and other factors. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. The way endothelial function altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.     

How much TCR does a T cell need?

Kinetic features of TCR:MHC/peptide interactions dictate their outcome in vitro, some important parameters of which include the number of molecules engaged and the duration of engagement. We explored the in vivo significance of these findings in transgenic mice expressing TCRs in a quantitatively and temporally controlled manner. As anticipated, reduced TCR levels resulted in attenuated reactivity, but response thresholds were substantially lower than expected-at as low as 1/20th the normal TCR numbers and with no indication of phenotypic skewing at suboptimal levels. We also studied survival of T lymphocytes stripped of their TCRs. Unlike B cells, T cells lacking antigen receptors did not die precipitously; instead, populations decayed gradually, just as previously reported in the absence of MHC molecules.     

How does epidermal pathology interact with mental state?

The hypothesis is presented that human emotional state is influenced by epidermal pathology via the release from epidermal keratinocytes of a wide variety of chemical mediators (including neurotransmitters) that act on the brain. It has long been recognized that epidermal keratinocytes play a key role in the function of the stratum corneum as an impermeable barrier, and that skin diseases such as atopic dermatitis and psoriasis, which cause itching, sleep disturbance and concern over appearance, are associated with depression and anxiety. On the other hand, epidermal keratinocytes are known to produce and release multiple cytokines and chemical mediators in response to barrier impairment or insult, such as environmental dryness or UV radiation. Elevation of plasma cytokines is associated with depression in cancer patients. Serum levels of oxytocin and glucocorticoid have been shown to influence mental state, and a recent study showed that glucocorticoid is generated in injured epidermis. Thus, there are multiple plausible pathways through which changes in skin can affect emotional state.     

How does psychotherapy influence personality? A theoretical integration

A given type of psychotherapy (e.g., psychodynamic) is associated with a set of specific change techniques (e.g., interpreting defenses, identifying relationship themes). Different change techniques can be conceived of as influencing different parts of personality (e.g., interpreting defense increases conscious awareness). An integrated model of personality is presented. Then, change techniques from different theoretical perspectives are assigned by judges to areas of personality the techniques are believed to influence. The results suggest that specific change techniques can be reliably sorted into the areas of personality. Thinking across theoretical perspectives leads to important new opportunities for assessment, therapy outcome research, and communication with patients concerning personality change.