-establishment of small animal proton and photon image-guided radiation experiments.

Theevolution of radiotherapy necessitates innovative platforms for preclinical investigation, bridging the gap between bench research and clinical applications. Understanding the nuances of radiation response, specifically tailored to proton and photon therapies, is critical for optimizing treatment outcomes. Within this context, preclinicalexperimental setups incorporating image guidance for both photon and proton therapies are pivotal, enabling the translation of findings from small animal models to clinical settings.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis.

Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice.

Vessel maturation schedule determines vulnerability to neuronal injuries of prematurity.

Premature birth is a major risk factor for multiple brain pathologies, notably periventricular leukomalacia (PVL), which is distinguished by bilateral necrosis of neural tissue around the ventricles and a sequela of neurological disturbances. The 2 hallmarks of brain pathologies of prematurity are a restricted gestational window of vulnerability and confinement of injury to a specific cerebral region. Here, we examined the proposition that both of these features are determined by the state of blood vessel immaturity.

Approaching clinical proteomics: current state and future fields of application in cellular proteomics.

Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges.

Changes in HDL-associated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation.

Objective: Lipoproteins modulate vascular cell function in inflammation. In this study, we analyzed whether plasma concentrations of lipoproteins and apolipoproteins in human sepsis are related to patient survival and the activation of blood monocytes and platelets.

Design: Observational study.

Approaching clinical proteomics: current state and future fields of application in fluid proteomics.

The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics.

Flow cytometric analysis of reticulated platelets.

Flow Cytometric Analysis of Reticulated Platelets (G. Matic, G. Rothe, and G.

Reduction of divinyl ether-containing polyunsaturated fatty acids in transgenic potato plants.

Oxygenated polyunsaturated fatty acids synthesized via the lipoxygenase pathway play a role in plant responses to pathogen attack. In solanaceous plants, the preferential stimulation of the 9-lipoxygenase pathway in response to pathogen infection leads to the formation of the divinyl ether-containing polyunsaturated fatty acids colneleic and colnelenic acid, as well as hydroxy and trihydroxy polyunsaturated fatty acids. To functionally assess the role of divinyl ethers, transgenic potato plants were generated which express an RNA interference construct directed against the pathogen-inducible 9-divinyl ether synthase.

Inhibitory effect of tumor cell-derived lactic acid on human T cells.

A characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity.

Inhibition of the neutrophil oxidative response by propofol: preserved in vivo function despite in vitro inhibition.

Background And Objective: Propofol has been shown to inhibit a variety of functions of neutrophils in vitro, but there is a lack of in vivo data. To analyse the effects of propofol on neutrophil function in vivo we chose to investigate cataract surgery since it represents a small surgical procedure with minimal immunomodulatory effects induced by surgery. We sought to analyse any immunosuppressive effects of propofol after short-term administration in vivo in comparison to local anaesthesia as well as to in vitro effects of propofol.

Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.

Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients.

[Differential diagnosis of platelet disorders].

Platelet disorders frequently represent a cause of bleeding disorders with a late manifestation and spontaneous bleeding. Disturbances of cellular hemostasis can be of quantitative nature due to an altered production or destruction of platelets. Qualitative disturbances can be associated with defects of adhesion, secretion or degranulation.

Evaluation of the antimicrobial activities of plant oxylipins supports their involvement in defense against pathogens.

Plant oxylipins are a large family of metabolites derived from polyunsaturated fatty acids. The characterization of mutants or transgenic plants affected in the biosynthesis or perception of oxylipins has recently emphasized the role of the so-called oxylipin pathway in plant defense against pests and pathogens. In this context, presumed functions of oxylipins include direct antimicrobial effect, stimulation of plant defense gene expression, and regulation of plant cell death.

Multicentre evaluation of stable reference whole blood for enumeration of lymphocyte subsets by flow cytometry.

BACKGROUND: Clinical indications for lymphocyte subset enumeration by flow cytometry include monitoring of disease progression and timing of therapeutic intervention in infection with human immunodeficiency virus. Until recently international standardisation has not been possible due to a lack of suitable stable reference material. METHODS: This study consisted of two trials of a stabilised whole blood preparation.

Overexpression of tropinone reductases alters alkaloid composition in Atropa belladonna root cultures.

The medicinally applied tropane alkaloids hyoscyamine and scopolamine are produced in Atropa belladonna L. and in a small number of other Solanaceae. Calystegines are nortropane alkaloids that derive from a branching point in the tropane alkaloid biosynthetic pathway.

Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA tetramer-based flow cytometry: a European multicenter evaluation.

Background: HLA class I peptide tetramers represent powerful diagnostic tools for detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the current multicenter study is the critical need to standardize tetramer flow cytometry if it is to be implemented as a routine diagnostic assay. Hence, the European Working Group on Clinical Cell Analysis set out to develop and evaluate a single-platform tetramer-based method that used cytomegalovirus (CMV) as the antigenic model.

Mild hyperthermia down-regulates receptor-dependent neutrophil function.

Mild hypothermia impairs resistance to infection and, reportedly, impairs phagocytosis and oxidative killing of unopsonized bacteria. We evaluated various functions at 33 degrees-41 degrees C in neutrophils taken from volunteers. Adhesion on endothelial cells was determined using light microscopy.

Differential effects of clindamycin on neutrophils of healthy donors and septic patients.

Antibiotics are frequently administered to ICU patients in case of bacterial infections. Little is known, however, about the interference of antibiotics with neutrophil host defence mechanisms in patients with sepsis and multiple organ dysfunction syndrome (MODS). With our study, evidence for differential clindamycin effects on neutrophils in healthy donors and septic patients without or with MODS was sought.

Cytokine upregulation of surface antigens correlates to the priming of the neutrophil oxidative burst response.

Background: Neutrophil activation is strongly related to organ dysfunction that occurs during systemic inflammatory responses. The aim of our study was to analyze the oxidative burst response in correlation to the up- and downregulation of N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) receptors and the surface antigens CD11b, CD62L, and CD66b as potential surrogate markers of the degree of neutrophil priming for an increased oxidative burst response induced by proinflammatory cytokines.

Methods: Blood was taken from healthy donors.

Blood leukocyte subsets and cytokine profile after autologous peripheral blood stem cell transplantation.

High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) includes the risk of infectious complications due to neutropenia and therapy-induced immune deviation. In order to understand early immune recovery in this situation, we analyzed the distribution of cell subsets by flow cytometry and we measured cytokine production in a whole blood assay stimulated with lipopolysaccharide (LPS) in order to induce monocyte (MO) activation in 43 patients with solid tumors or lymphoma treated with two cycles of high-dose chemotherapy and PBSCT. Blood was collected at the following time points: before start of mobilization chemotherapy, before and after high-dose chemotherapy, and 10 and 30 days after PBSCT.

Alkaloids in plants and root cultures of Atropa belladonna overexpressing putrescine N-methyltransferase.

Putrescine N-methyltransferase (PMT) is the first alkaloid-specific enzyme for nicotine and tropane alkaloid formation. The pmt gene from Nicotiana tabacum was fused to the CaMV 35S promoter and integrated into the Atropa belladonna genome. Transgenic plants and derived root cultures were analysed for gene expression and for levels of alkaloids and their precursors.

Autologous tandem transplantation: almost complete reduction of neutropenic fever following the second transplantation by ex vivo expanded autologous myeloid postprogenitor cells.

Reduced post-transplant performance status because of infectious complications is still a problem following autologous peripheral blood stem cell transplantation (aPBSCT). In this study, a tandem transplantation scheme for 15 patients with breast cancer including etoposide (1500 mg/m(2)), ifosfamide (12 g/m(2)) and carboplatin (1500 mg/m(2)) as conditioning regimens, followed by aPBSCT, was used to evaluate the potential clinical benefit of the additional retransfusion of low numbers of ex vivo expanded committed myeloid postprogenitor cells (PPCs) (median 408 x 103 CFU-c/kg BW, range 0.93-1995) following the second transplantation.