From psychobiological stress research to neuropsychoimmunology]

Psychoimmunology--a neologism--is a short term for the growing evidence that there are multiple interactions between central nervous system, vegetative nervous system, endocrinological system and immunological system. In the history of research the psychobiological stress concept of Hans Selye has been the most powerful basis for the ongoing empirical work in investigating aspects of systemic processes of psychoimmunology. Nowadays there is no doubt that the immunological system must not be seen as an independently functioning organic system. Simple causal links (like stressor-strain-relations) are not useful in explaining the complex interactions that we observe when biological phenomena simultaneously are taken into consideration. Especially with psychological stressors--the most frequent kind of troubles in our contemporary way of life--we have to stress the importance of the individual's evaluation of potentially stressful situations. In a wide variety a stressor becomes the potential of provoking strain because of my own appraisal. This multiple-step-process of appraisal is dependent on my coping abilities and coping strategies regarding an objectively or subjectively dangerous situation. Although there are common genetic and predispositional factors influencing the stress reaction we have to focus more on psychological phenomena, especially the possibility of conditioning stress reactions. As we know by empirical data some reactions of the immunological system are also influenced by learning processes like classical conditioning procedures. This knowledge may be used for a better understanding of a lot of chemical findings.     

A contribution to the natural history of breast cancer. V. Bilateral primary breast cancer: incidence, risks and diagnosis of simultaneous primary cancer in the opposite breast

Tissue from contralateral breast was taken from 505 patients with invasive breast cancer. Every 5th patient had simultaneous carcinoma in the opposite breast, 7.7% (39/505) had invasive cancer, and 13.1% (66/505) had carcinoma in situ. Invasive cancers in the opposite breast were diagnosed at an earlier stage as compared with the neoplasm of the primary breast. However, 26% of the patients already had positive axillary nodes. The following risk indicators of the bilateral disease were found: age at time of diagnosis, histologic type of tumours, familial breast cancer, suspicious mammography, P2/DY-breast parenchymal pattern (Wolfe) and multicentric cancer of primary breast. Our findings support the proposal to consider bilaterality of breast cancer as a sign of systemic disease of the breasts, involving the ductal and lobular system within eight quadrants of a paired organ (Ober).     

Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis

Bacterial meningitis causes neuronal apoptosis in the hippocampal dentate gyrus, which is associated with learning and memory impairments after cured disease. The execution of the apoptotic program involves pathways that converge on activation of caspase-3, which is required for morphological changes associated with apoptosis. Here, the time course and the role of caspase-3 in neuronal apoptosis was assessed in an infant rat model of pneumococcal meningitis. During clinically asymptotic meningitis (0-12 h after infection), only minor apoptotic damage to the dentate gyrus was observed, while the acute phase (18-24 h) was characterized by a massive increase of apoptotic cells, which peaked at 36 h. In the subacute phase of the disease (36-72 h), the number of apoptotic cells decreased to control levels. Enzymatic caspase-3 activity was significantly increased in hippocampal tissue of infected animals compared to controls at 22 h. The activated enzyme was localized to immature cells of the dentate gyrus, and in vivo activity was evidenced by cleavage of the amyloid-beta precursor protein. Intracisternal administration of the caspase-3-specific inhibitor Ac-DEVD-CHO significantly reduced apoptosis in the hippocampal dentate gyrus. In contrast to a study where the decrease of hippocampal apoptosis after administration of a pan-caspase inhibitor was due to downmodulation of the inflammatory response, our data demonstrate that specific inhibition of caspase-3 did not affect inflammation assessed by TNF-alpha and IL-1beta concentrations in the cerebrospinal fluid space. Taken together, the present results identify caspase-3 as a key effector of neuronal apoptosis in pneumococcal meningitis.