Antitumorale Wirkung von Interferonen und Interleukinen in Kombination mit Strahlentherapie

BACKGROUND: During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. METHOD: The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. RESULTS: Recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e. g., the induction of IFN-gamma expression in Th1 cells by IL-12. CONCLUSION: The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.     

Exposure to allergens of different cattle breeds and their relevance in occupational allergy

Introduction  

Cattle are an important source of allergens in the working area of farmers. Asthma caused by cow allergens is a significant occupational problem. Yet in allergological testing, the results of in vivo and in vitro diagnostic tests are often inconsistent even in cases with clearly cattle-related symptoms.     

Proximal myotonic myopathy

Three Swedish patients with proximal muscle weakness, myotonia and lack of CTG expansion on genetical analysis are presented. Clinical neurological and neurophysiological examination and muscle biopsy were performed. There was an indication of autosomal dominant inheritance in 2 of the 3 patients. The main symptoms and clinical findings in the 3 patients were weakness of the proximal muscles, myotonia, muscle stiffness, muscle pain and muscle atrophy. Neurophysiological examination showed myotonic bursts and muscle biopsy snowed a variation of fibre sizes, an increased number of muscle fibres with centralized nuclei and scattered atrophic muscle fibres. Laboratory data showed elevated CK, GT and LD in 1 patient. Before genetical analysis was performed, all 3 patients had been diagnosed as atypical cases of myotonic dystrophy. However, the symptoms, clinical signs, laboratory data, electrophysiological and muscle biopsy findings were compatible with proximal myotonic myopathy (PROMM).     

Neuropsychological changes during steady-state drug use,withdrawal and abstinence in primary benzodiazepine-dependent patients

Impairment on neuropsychological tests during steady-state drug use and withdrawal, and after discontinuation of benzodiazepines, was studied in primary benzodiazepine-dependent patients. One group of patients was tested before and the other group after the initiation of a gradual tapering-off of the drug, and both groups were tested approximately 1 year later. At the initial assessment, both groups of patients showed impairment on most of the tests of general intelligence and on several of the tests in the Halstead-Reitan battery, as well as on a test of nonverbal memory, in comparison with healthy controls. At follow-up the patient groups had reached the level of the control group. This study confirmed earlier observations of neuropsychological deficits in long-term benzodiazepine-using patients and demonstrated that these changes are at least partly reversible by discontinuing drug intake.     

Release of vasopressin from supraoptic neurons within the median eminence in vivo. A combined microdialysis and push-pull perfusion study in the rat

The present study was designed to investigate whether or not arginine vasopressin (AVP) is released from magnocellular neurons within the median eminence (ME) in vivo. Urethane-anesthetized adult male Wistar rats were equipped with a microdialysis probe aimed at the supraoptic (SON) or paraventricular nucleus (PVN), a push-pull perfusion probe resting in the ME, and a blood microdialysis probe within the jugular vein. Dialysis of the SON (but not the PVN) with Ringer's solution containing 56 mmol l⁻¹ K⁺ resulted in an increase in AVP release within the ME (to 492 ± 192% of release during basal conditions,P < 0.05) and into blood (to 138 ± 9%,P < 0.01) whereby the release probably occurred from axonal swellings and nerve terminals of supraoptic neurons which project through the internal zone of the ME to the posterior pituitary. The calculated amount of AVP released into the extracellular fluid of the ME was high enough (approximately 1 pg/μ1) to hypothesize that the neuropeptide could enter the portal blood capillaries in physiologically relevant concentrations. Taken together, the present study indicates that activation of magnocellular neurons is accompanied by release of AVP within the median eminence. We assume that AVP released in this way might mediate a communication between the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis in response to selected stressful stimuli.     

Personality and quality of life: The importance of optimism and goal adjustment

This article concerns the relations between personality and quality of life. In the first part, we discuss different conceptualizations of personality and quality of life. We argue that personality affects quality of life by influencing how people approach and react to critical life situations. In the second part, we address the beneficial role played by two individual difference variables in promoting quality of life: dispositional optimism and goal adjustment. Literature is reviewed demonstrating that dispositional optimism facilitates subjective well-being and good health, mediated by a person's coping behaviors. In addition, we discuss studies that examine people who confront unattainable goals. The reported evidence supports the conclusion that individual differences in people's abilities to adjust to unattainable goals are associated with a good quality of life.     

Studies on the immunological effects of fatty alcohols--I. Effects of n-hexacosanol on murine macrophages in culture.

n-Hexacosanol (hexa), a long chain fatty alcohol extracted from Hygrophila erecta, has proved to possess neurotrophic activities on cultured neurons, and to attenuate the degeneration of cholinergic neurons after injury. In the present study, we show that hexa has also interesting properties on macrophages, a cell type largely represented in the brain: when added to mice resident peritoneal macrophages, it provokes significant morphological changes, and increases their phagocytosis capacity. These results may indicate that some membrane properties involved in these different effects and in macrophage functions are affected by n-hexacosanol, but other sites of action could also be considered.     

CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric,pancreatic, and esophageal carcinomas

CD97 expression is related closely to the dedifferentiation and tumor stage in thyroid carcinomas. We systematically examined the role of CD97 and its closest relative, EMR2, in normal and malignant gastric, esophageal, and pancreatic tissue. The normal tissues were EMR2-, whereas CD97 was expressed slightly in the parietal cells of gastric mucosa and in exocrine pancreatic cells. Interestingly, intralobular and interlobular pancreatic ducts were CD97+. All tumors were EMR2-. CD97 was expressed by 44 of 50 gastric, 14 of 18 pancreatic, and 10 of 13 esophageal carcinomas. Of the 44 gastric cancers, 27 showed disseminated or scattered tumor cells at the invasion front with stronger CD97 expression than tumor cells located in solid tumor formations. There was no correlation between CD97 levels in the tumors or soluble CD97 in the serum samples and the clinicopathologic features of the patients. Taken together, significant numbers of gastric, esophageal, and pancreatic carcinomas are CD97+, whereas its homolog, EMR2, does not have any role in such tumors.