Potential of Ni(II)-NTA-modified poly(ethylene imine) glycopolymers as carrier system for future dendritic cell-based immunotherapy.

Dendritic cells (DCs) play a crucial role in the development of cell-mediated immunotherapy due to their ability to induce and maintain strong immune responses. In our study, we evaluated a biocompatible Ni(II)-NTA-modified poly(ethylene imine) dendritic glycopolymer (Ni(II)-NTA-DG) as new carrier system to increase the antigen uptake into iDCs for future DC-based immunotherapy. Ni(II)-NTA-DG led to an increase in His6-Gp160 uptake in monocytes and iDCs, where His6-Gp160 is localized in the early endosomal and lysosomal compartments. Ni(II)-NTA-DG and the formed polyplexes induced an activation of iDCs, showing an increasing expression of costimulatory molecules CD86, CD80, and proinflammatory cytokines IL-6 and IL-8. Beside no influencing effect of Ni(II)-NTA-DG and polyplexes on the maturation of antigen-bearing DCs, the mature peptide bearing DCs remained their ability to migrate along a gradient of CCR7 ligands. Thus, Ni(II)-NTA-DG with advancing biological properties is a promising carrier system for the future application in DC-based immunotherapy.

IDO1 and IDO2 gene expression analysis by quantitative polymerase chain reaction.

Immunomodulatory properties of IDO1 relate to tryptophan catabolism. The degradation of tryptophan by IDO1 leads to suppression of T cell responses. Recently, another enzyme with IDO-like activity, indoleamine 2,3-dioxygenase-like-protein 1 (INDOL1, IDO2), has been described in both mice and humans. In order to study the gene expression of IDO1 and IDO2, we have developed a quantitative PCR (qPCR) assay. In an exploratory application to the study of the differential expression of IDO1 and IDO2 by professional antigen-presenting cells and MSCs (mesenchymal stromal cells) under the influence of interferon-γ (IFN-γ) and T-lymphocyte conditioned media (TCM), substantial differences were observed. IDO expression measured by qPCR was valid and reliable in the cell types investigated. Further studies are needed to delineate factors driving IDO expression in MSCs.

Homing in the ant Cataglyphis bicolor.

Cataglyphis bicolor, an ant widely distributed in North Africa and the Near East, orient to the sun as well as to visual patterns of the environment. These two mechanisms can be separated. Foraging ants (hunters) orient to terrestrial cues as long as possible, and only after these have become ineffective do they switch over to the menotactical sun orientation. In the digging individuals, however, the visual knowledge of locality is significantly inferior to that of the hunters. Diggers vary considerably in size, but hunters belong to the largest size group. In addition, the largest and smallest individuals orient differently toward black and white areas and stripe patterns.

Oceili: a celestial compass in the desert ant cataglyphis.

In addition to multifaceted lateral compound eyes, most insects possess three frontal eyes called ocelli. Each ocellus has a single lens, as does the vertebrate eye. The ocelli of some flying insects, locusts and dragonflies, have been shown to function as horizon detectors involved in the visual stabilization of course. In a walking insect, the desert ant Cataglyphis, it is now shown that the ocelli can read compass information from the blue sky. When the ant's compound eyes are occluded and both sun and landmarks are obscured, the ocelli, using the pattern of polarized light in the sky as a compass cue, help in guiding the ant back home.

Bortezomib significantly impairs the immunostimulatory capacity of human myeloid blood dendritic cells.

Bortezomib is a potent drug for the treatment of multiple myeloma. Its anti-tumor activity is mediated by proteasome inhibition leading to decreased cell proliferation and induction of apoptosis. However, an unimpaired proteasomal function plays a crucial role for the induction of anti-tumor immunity by dendritic cells (DCs), which are currently used for therapeutic vaccination against various tumors including myeloma. In the present study, we investigated the impact of bortezomib on the immunostimulatory capacity of 6-sulfo LacNAc (slan) DCs, which represent a major subset of human blood DCs. We demonstrated that this proteasome inhibitor efficiently impairs the spontaneous in vitro maturation of slanDCs and the release of tumor necrosis factor (TNF)-alpha as well as interleukin (IL)-12 upon lipopolysaccharide (LPS) stimulation. Functional data revealed that bortezomib profoundly inhibits slanDC-induced proliferation and differentiation of CD4(+) T cells. In addition, the capacity of slanDCs to promote interferon-gamma secretion and tumor-directed cytotoxicity of natural killer (NK) cells is markedly impaired by bortezomib. These results provide evidence that bortezomib significantly reduces the ability of native human blood DCs to regulate innate and adaptive anti-tumor immunity and may have implications for the design of therapeutic strategies combining DC vaccination and bortezomib treatment.

Calibration of vector navigation in desert ants.

Desert ants (Cataglyphis sp.) monitor their position relative to the nest using a form of dead reckoning [1] [2] [3] known as path integration (PI) [4]. They do this with a sun compass and an odometer to update an accumulator that records their current position [1]. Ants can use PI to return to the nest [2] [3]. Here, we report that desert ants, like honeybees [5] and hamsters [6], can also use PI to approach a previously visited food source. To navigate to a goal using only PI information, a forager must recall a previous state of the accumulator specifying the goal, and compare it with the accumulator's current state [4]. The comparison - essentially vector subtraction - gives the direction to the goal. This whole process, which we call vector navigation, was found to be calibrated at recognised sites, such as the nest and a familiar feeder, throughout the life of a forager. If a forager was trained around a one-way circuit in which the result of PI on the return route did not match the result on the outward route, calibration caused the ant's trajectories to be misdirected. We propose a model of vector navigation to suggest how calibration could produce such trajectories.

Neurobiology of polarization vision.

Insects can perceive the pattern of polarized light (e-vector pattern) in the sky and use it as a compass. To accomplish this navigational task they employ a specialized part of the retina in which the polarization analysers (ultraviolet receptors) are arranged in a way that mimics, by and large, the distribution of e-vector directions in the sky. By sweeping this 'matched polarization filter's across the sky, the insect translates the complex spatial information provided by the celestial e-vector patterns into rather simple temporal modulations of summed receptor outputs. This mechanism provides a striking example of peripheral coding by matched filtering in sensory systems.

Restrictions on rotational and translational diffusion of pigment in the membranes of a rhabdomeric photoreceptor.

Individual, isolated rhabdoms from dark-adapted crayfish (Orconectes, Procambarus) were studied with a laterally incident microbeam that could be placed in single stacks of microvilli. Concentration gradients of metarhodopsin along the lengths of microvilli were produced by local bleaches, accomplished by irradiation with small spots of orange light at pH 9 in the presence of glutaraldehyde or formaldehyde. No subsequent redistribution of pigment was observed in the dark, indicating an absence of translational diffusion. On the basis of comparison with other systems, glutaraldehyde, but not formaldehyde (0.75%), would be expected to prevent diffusion of protein in the membrane. Under the same conditions photodichroism is observed, indicating an absence of free Brownian rotation. Photodichroism is larger in glutaraldehyde than in formaldehyde, suggesting that the bifunctional reagent quiets some molecular motion that is present after treatment with formaldehyde. Quantitative comparison of photodichroism with mathematical models indicates that the pigment absorption vectors are aligned within +/- 50 degrees of the microvillar axes and are tilted into the surface of the membrane at an average value of about 20 degrees. The photoconversion of rhodopsin to metarhodopsin is accompanied by an increase in molar extinction of about 20% at the lambda maxand a reorientation of the absorption vector by several degrees. The transition moment either tilts further into the membrane or loses some of its axial orientation, or both. The change in orientation is 3.5 time larger in formaldehyde than in glutaraldehyde.

Middle-scale navigation: the insect case

What is the large-scale spatial representation that insect foragers such as bees and ants form of their wider nest environs? This is the principal question which the following contributions aim to answer.

Optical scaling in conspecific Cataglyphis ants

This study examines the effects of body size variation on the optical properties of the compound eyes of visually guided desert ants belonging to the genus Cataglyphis. Although linear head size may vary by a factor of 2 within conspecific workers and most optical parameters change accordingly, the extent of the visual field remains constant. Comparative measurements carried out on workers of three species (C. albicans, C. bicolor and C. fortis) and on reproductive females and males of one species (C. bicolor) show that the form (size and shape) of the visual field is highly characteristic for each caste/species. A constant visual field is realised by reciprocal scaling rules for the number of ommatidia and the angular spacing of ommatidia. While larger ants have more ommatidia per compound eye, interommatidial angles are reduced accordingly, thus giving rise to a constant visual field. Among conspecific ant workers, the relationship between spatial visual acuity and eye size is similar to that found in interspecific comparisons and reflects optical constraints imposed on the design of the compound eye. Mapping of spatial visual directions onto the compound eye surface reveals a characteristic, inhomogeneous distribution of interommatidial spacing, particularly a foveal band with increased visual acuity in the vertical direction. This 'visual stretch' viewing the horizon is similar to that found in a variety of flying insects. Although, among conspecific workers, both the number of ommatidia and the interommatidial angles vary with varying head size, the overall pattern of interommatidial spacing is maintained so that corresponding positions on the compound eye of small and large individuals look in equivalent directions in space. These findings are in accordance with the observation that the shape of the compound eye surface, as expressed by the radius of curvature along cross sections, is similar in small and large ants.

Visual navigation in insects: coupling of egocentric and geocentric information

Social hymenopterans such as bees and ants are central-place foragers; they regularly depart from and return to fixed positions in their environment. In returning to the starting point of their foraging excursion or to any other point, they could resort to two fundamentally different ways of navigation by using either egocentric or geocentric systems of reference. In the first case, they would rely on information continuously collected en route (path integration, dead reckoning), i.e. integrate all angles steered and all distances covered into a mean home vector. In the second case, they are expected, at least by some authors, to use a map-based system of navigation, i.e. to obtain positional information by virtue of the spatial position they occupy within a larger environmental framework. In bees and ants, path integration employing a skylight compass is the predominant mechanism of navigation, but geocentred landmark-based information is used as well. This information is obtained while the animal is dead-reckoning and, hence, added to the vector course. For example, the image of the horizon skyline surrounding the nest entrance is retinotopically stored while the animal approaches the goal along its vector course. As shown in desert ants (genus Cataglyphis), there is neither interocular nor intraocular transfer of landmark information. Furthermore, this retinotopically fixed, and hence egocentred, neural snapshot is linked to an external (geocentred) system of reference. In this way, geocentred information might more and more complement and potentially even supersede the egocentred information provided by the path-integration system. In competition experiments, however, Cataglyphis never frees itself of its homeward-bound vector - its safety-line, so to speak - by which it is always linked to home. Vector information can also be transferred to a longer-lasting (higher-order) memory. There is no need to invoke the concept of the mental analogue of a topographic map - a metric map - assembled by the insect navigator. The flexible use of vectors, snapshots and landmark-based routes suffices to interpret the insect's behaviour. The cognitive-map approach in particular, and the representational paradigm in general, are discussed.

An improved extraction method for plasma steroid hormones.

An easy and rapid column chromatographic method for the extraction of steroid hormones from plasma is presented. It permits the nearly quantitative separation of the steroids in a single step with smaller expenditure of time and work as compared to the usual liquid-liquid extraction. Problems of emulsions are eliminated. Furthermore, fractionated separation of hormones from plasma is possible. A simple procedure for the selective extraction of estriol (isolated from estrone and estradiol) is described.

Bees perceive illusory colours induced by movement.

Certain black-and-white patterns, when rotated at appropriate speeds, can create the artificial perception of hues. We report that this illusion is not confined to human vision, but is also perceived by an insect, the honeybee. The findings suggest that certain features underlying the processing of colour information are shared by man and bee.

Selected responses of hypertension-sensitive and resistant rats to inhaled acrolein.

The Dahl selected rat lines, one susceptible to salt-induced hypertension (DS) and the other resistant to salt-induced hypertension (DR), were exposed to filtered air, 0.4, 1.4, or 4.0 ppm acrolein for 6 h/day, 5 days/week for 62 days. All of the DS rats exposed to 4.0 ppm acrolein died within the first 11 days, while 60% of the DR animals survived the duration of the study. Neither dose dependent blood pressure changes nor altered behavioral characteristics were evident in either rat strain following acrolein exposure. Exposure to 4.0 ppm acrolein increased the level of several serum enzymes in the DR rats which survived. This concentration of acrolein also led to pulmonary edema and a significant increase in lung connective tissue in these animals. There was a marked difference in the pulmonary pathology observed in DS and DR rats exposed to 4.0 ppm acrolein. The lungs of moribund DS rats exhibited severe airway epithelial necrosis with edema and hemorrhage, while surviving DR rats primarily showed a proliferative change. Following exposure to 0.4 and 1.4 ppm acrolein, both rat lines displayed similar pathologic changes. Epithelial hyperplasia and/or clusters of macrophages were usually found near terminal bronchiolar areas. These findings suggest that further investigation of the physiopathologic sensitivity of the DS rat line may elucidate a model for investigating the underlying characteristics of stress susceptible populations.

The impact of inhaled acrolein on hypertension-sensitive and resistant rats.

The Dahl selected rat lines, one susceptible to salt-induced hypertension (DS) and the other resistant to salt-induced hypertension (DR), were subchronically exposed to filtered air, 0.4, 1.4, or 4.0 ppm acrolein. All of the DS rats exposed to 4.0 ppm acrolein died within the first 11 days, while 60% of the DR animals survived. Neither dose dependent blood pressure changes nor altered behavioral characteristics were evident following acrolein exposure. Exposure to 4.0 ppm acrolein increased the level of several serum enzymes. This concentration of acrolein also led to pulmonary edema and a significant increase in lung connective tissue. There was a marked difference in the pulmonary pathology observed in DS and DR rats exposed to 4.0 ppm acrolein. The lungs of the DS rats exhibited severe airway epithelial necrosis with edema and hemorrhage, while surviving DR rats primarily showed a proliferative change. Following exposure to 0.4 to 1.4 ppm acrolein, both rat lines displayed similar pathologic change. Epithelial hyperplasia and/or clusters of macrophages were usually found near terminal bronchiolar areas. These findings suggest that further investigation of the physiopathologic sensitivity of the DS rat line may elucidate a model for investigating the underlying characteristics of stress susceptible populations.

Anesthetic considerations for the patient with Huntington's disease.

Huntington's disease (HD) is an autosomal, dominantly inherited disease with symptoms manifesting late in life. Patients suffer from motor dysfunction and progressive mental deterioration. HD patients present a number of anesthetic challenges as they are usually elderly, malnourished, and at risk for aspiration. Previous reports on anesthesia for patients with HD have warned that sodium pentothal and succinylcholine cause prolonged apnea in this patient population. In this article, a 78-year-old female presented for cataract extraction. Although her movement disorder was under good control with haloperidol, a general anesthetic was chosen for the procedure in order to ensure a tranquil surgical field. This article presents the successful management of a patient with HD using a balanced anesthetic technique combining judicious amounts of narcotics and barbiturates with isoflurane.

Life threatening ventricular dysrhythmias: intervention with bretylium tosylate.

The impact of psychogenic and physical stressors has been shown to have a negative effect on cardiovascular homeostasis (Figure 2). As CRNAs, we have a responsibility to maintain the patient's equilibrium under the stress-provoking conditions of surgery. Experience in coronary care units over the last 16 years has shown that the majority of patients who develop primary ventricular fibrillation during AMI can be rapidly resuscitated by prompt defibrillation. Only in a small number of patients does ventricular tachycardia or ventricular fibrillation become recurrent or resistant to treatment. It is in this small number that bretylium has proven itself to be a life-saving treatment.

Evaluation of esmolol and fentanyl in controlling increases in heart rate and blood pressure during endotracheal intubation.

Laryngoscopy and intubation cause an adrenergic response manifested by tachycardia and hypertension. Various pharmacological agents, including fentanyl, have been administered prior to induction in an attempt to attenuate the adrenergic response but they all have limitations. Esmolol, an ultrashort-acting cardioselective beta blocker, has been administered by infusion to successfully protect surgical patients from the stresses of intubation. The objective of our study was to determine if esmolol would be equally effective when administered in a bolus with and without fentanyl. Forty-four ASA I and II females undergoing elective surgery were randomly divided into four groups and received the following agents prior to intubation: Group 1-esmolol 1 mg/kg and fentanyl 2 micrograms/kg, Group 2-placebo (normal saline), Group 3-esmolol 1 mg/kg and Group 4-fentanyl 3.5 micrograms/kg. Groups 1 and 4, which received fentanyl, demonstrated significantly less elevation in blood pressure. Esmolol appeared to attenuate increases in heart rate. Esmolol has a tissue distribution time of 2 minutes and an elimination half-life of 9 minutes. The window of its availability to the tissues is narrow, and timing of bolus administration is more critical than in administration by infusion. Doses in excess of 1 mg/kg appear to be necessary for effective control of heart rate. However, when used with fentanyl, esmolol provides effective protection against the adrenergic response to laryngoscopy and intubation.