[Immunological foundations of modern (tumor) immunotherapy]. / Immunologische Grundlagen moderner (Tumor­)Immuntherapie.

Understanding the fundamental principles underlying the development, activation, regulation, plasticity, diversification, and even death of immune cells is a prerequisite for the development of targeted strategies to modulate the immune system in the fight against cancer. As our understanding of these processes evolves, their translation has led to the development of pioneering therapeutic approaches in the treatment of malignant diseases.

Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells.

The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation. Hence, the classification of Treg cells might need to be further extended by Treg cell subsets that are functionally and phenotypically polarized by their residency. In this review, we discuss recent findings on these tissue-resident Treg cell subsets and how these cells may operate in a tissue- and context-dependent manner.

Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine.

The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.

Dimenhydrinate for prevention of post-operative nausea and vomiting in female in-patients.

Dimenhydrinate is an inexpensive antihistaminic drug, that is frequently used as an anti-emetic during anaesthesia. The popularity of the drug is contrasted by the lack of modern studies concerning its efficacy in reducing the incidence of post-operative nausea and vomiting. Thus, dimenhydrinate was compared with placebo in this prospective, randomized, double-blind study. One hundred and thirty-three female in-patients were studied. They were stratified according to the type of surgery (laparoscopic cholecystectomy, thyroid resection or knee arthroscopy) to ensure an homogeneous distribution in both groups. General anaesthesia was induced with etomidate, fentanyl, vecuronium and maintained with enflurane in N2O/O2. Neuromuscular block was reversed with pyridostigmine/atropine. Patients in the dimenhydrinate group (n = 67) received 62 mg dimenhydrinate intravenously after induction of anaesthesia. Placebo patients (n = 66) received saline. Administration of dimenhydrinate (and placebo) was repeated three times during the 48-h study to mitigate the short half-life of the drug. Post-operative analgesia and anti-emetic rescue medication was standardized. Episodes of vomiting, retching and the need for additional anti-emetics were recorded. Nausea was assessed using a 10-cm visual analogue scale. Post-operative nausea and vomiting was rated as 'none', 'mild', 'moderate' and 'severe' using a fixed scoring algorithm. There were no differences between the two groups with regard to biometric data, type of surgery and distribution of risk factors for developing post-operative nausea and vomiting. In the dimenhydrinate group, more patients remained completely free from post-operative nausea and vomiting compared with placebo (dimenhydrinate: 38.8%; placebo: 15.1%; P = 0.004). The incidence of severe post-operative nausea and vomiting was also reduced from 39.4% to 14.9%. No relevant side effects were observed. Intra-operative dimenhydrinate, followed by three further administrations after surgery, reduces the incidence and the severity of post-operative nausea and vomiting without side effects. However, there still remained an unacceptable high number of patients who were not prevented completely from experiencing post-operative nausea and vomiting.

Protein binding of palmitate measured by transmembrane diffusion through polyethylene.

Thin polyethylene membranes permit ready diffusion of protonated long-chain fatty acids but are impermeable to protein and ions. This circumstance recommends polyethylene for measuring the free fraction of fatty acids in the presence of a binding protein and for estimating the ionization constant with which to compute the equilibrium constant for the binding of fatty acid anions. As an example of this approach we report the binding of tracer palmitate to bovine albumin and bovine beta-lactoglobulin. We find a binding constant for the high-affinity site on albumin that is close to that calculated by others from heptane:H2O partition ratios. Our procedure is simpler, however, and free of the theoretical objection that heptane may alter the binding characteristics of the protein. Our estimate of the pKa for palmitic acid is 4.9, a finding that conforms to the widely predicted but heretofore unconfirmed expectation that long-chain fatty acids should have a pKa of about 4.8. Unidirectional flux measurements exclude direct exchange of palmitate between albumin and polyethylene.