Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

CGP 6809 — A new nitrosoureido-sugar derivative with activity in human tumor xenografts

Summary CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)--d-glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats [14]. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s. c. in nude mice. The p. o. administration of 125 mg/kg per day for 10–15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i. p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissure sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.Supported in part by grant PTB 8467 from the Bundesminister für Forschung und Technologie, Bonn, FRG     

Differential Fear of Cardiopulmonary Sensations in Emergency Room Noncardiac Chest Pain Patients

Fear of bodily sensations has received extensive attention in relation to panic disorder, and more recently, other types of anxiety pathology and chronic pain problems. Extending this work, the present study examined fear of bodily sensations and its underlying dimensions in emergency room patients with Noncardiac Chest Pain (NCCP; n = 63). We posited a differential specificity hypothesis, expecting that specific cardiopulmonary fears would be more strongly associated with NCCP symptoms relative to other bodily fears. As hypothesized, participants reported cardiopulmonary sensations as significantly more fear-provoking than numbness, dissociation, and gastrointestinal sensations. Additionally, regression analysis indicated that after accounting for theoretically relevant demographic variables and health status, cardiopulmonary fear was the best predictor of a composite index of cardiac complaints intensity, even after removing variance related to the absolute number of cardiac complaints. We discuss these findings in relation to the specific role for the fear of cardiopulmonary sensations in chest pain complaints, with implications for better understanding the underlying psychological processes involved in NCCP.     

Epidermal T lymphocytes--ontogeny, features and function.

Conclusions The murine epidermis contains a network of Thy-1⁺ dendritic T cells. These T cells arise from early fetal stem cells and differentiate in the fetal or neonatal thymic or epidermal microenvironment. Their lack of expression of CD5, CD4, and CD8 antigens, as well as their virtually exclusive expression of a CD3/TCR V3/V1 complex, distinguishes DETC from the bulk of peripheral T cells.The early appearance of TCR / cells in ontogeny, the lack of expression of CD4 and CD8 antigens, and the relative paucity of and genes compared to and genes, indicates that / T cells provide a phylogenetically primitive, broadly acting, and poorly discriminating immunologic defense system. In this system, recognition of antigen is not restricted by classical MHC class I and class II antigens, but may occur in the context of relatively nonpolymorphic restricting elements, such as Qa [82], Tla [10] or CD1 [62]. This rather primitive immune system provided by DETC may serve to protect the epidermal integrity. Upon recognition of self proteins released following epidermal injury, DETC may become activated and assist in the removal of altered cells. In this limited fashion, the epidermis may be an independently competent immunologic system. However, the fact that the TCR repertoire of DETC does not allow for the recognition of antigenic peptides in conjunction with MHC moieties excludes the possibility that the diverse immune response elicited by topical contact with foreign antigens is mediated by DETC.Whether this statement also applies to the human epidermis cannot be answered at the present time. Let us consider a few plausible concepts concerning derivation and function of human epidermal T cells. First, one could postulate that in early ontogeny, the human epidermis harbors a small, indigenous population of naive T lymphocytes with monomorphic TCR representing an analogue to murine DETC. These cells could function in a manner similar to that proposed for murine DETC. They may even persist into adult life, so far undetected because they would be outnumbered by immigrating polymorphic T cells from peripheral lymphoid organs. Second, it is conceivable that the human epidermis contains an indigenous population of naive T lymphocytes with a polymorphic TCR repertoire representing a phylogenetically advanced analogue to murine DETC. Although equipped with TCR allowing antigen recognition in the context of MHC, their density is probably too low to make them an effective host defense system against the multitude of environmental antigens presented by Langerhans cells. One could rather assume that they proliferate upon recognition of self antigens occurring in a perturbed epidermis. The autoreactivity of these cells may not necessarily be beneficial. Finally, the fact that the entry of circulating HECA-452⁺ memory cells into the skin is dependent upon the injury-induced ELAM-1 expression by endothelial cells of the dermal microvasculature could indicate that all T cells present in adult human epidermis are recruited upon alteration of the skin. Following this reasoning, the human epidermis should not be regarded as a complete, self-sustaining immunologic organ but rather as a homing site for and a target of lymphocytes antigenically sensitized in peripheral lymphoid organs.     

Neck proprioception compensates for age-related deterioration of vestibular self-motion perception

Vestibular functions are known to show some deterioration with age. Vestibular deterioration is often thought to be compensated for by an increase in neck proprioceptive gain. We studied this presumed compensatory mechanism by measuring psychophysical responses to vestibular (horizontal canal), neck and combined stimuli in 50 healthy human subjects as a function of age (range 15–76 years). After passive horizontal rotations of head and/or trunk (torso) in complete darkness (dominant frequencies 0.05, 0.1, and 0.4 Hz), subjects readjusted a visual target to its remembered prerotational location in space. (1) Vestibular-only stimulus (whole-body rotation); subjects' responses were shifted towards postrotatory body position, this only slightly at 0.4 Hz and pronounced at 0.1 and 0.05 Hz. These errors reflect the known physiological drop of vestibular gain at low rotational frequency. They exhibited a slight but significant increase with age. (2) Neck-only stimulus (trunk rotated, head stationary); the responses showed errors similar to those upon vestibular stimulation (with offset towards postrotatory trunk position) and this again slightly more with increasing age. (3) Vestibular-neck stimulus combination during head rotation on stationary trunk; the errors were close to zero, independent of stimulus frequency and the subjects' age. (4) Opposite stimulus combination (trunk rotated in the same direction as the head, but with double amplitude); the errors were clearly enhanced, essentially reflecting the sum of those with vestibular-only and neck-only stimulation. Taken together, we find a parallel increase in neck- and vestibular-related errors with age, in seeming contrast to previous studies. We explain our and the previous findings by a vestibular-neck interaction model in which two different neck signals are involved. One neck signal is used, in combination with the vestibular signal, for estimating trunk-in-space rotation. It is internally shaped to always match the vestibular signal, so that these two signals cancel each other out when summed during head rotation on stationary trunk. Because of this matching, perceived trunk stationariness during head rotation on the stationary trunk is independent of vestibular deterioration (related to stimulus frequency, age, ototoxic medication, etc.). The other neck proprioceptive signal, coding head-on-trunk rotation, is superimposed on the estimate of trunk-in-space rotation, thereby yielding a notion of head-in-space. This neck signal remains essentially unchanged with vestibular deterioration. Generally, we hold that the transformation of the vestibular signal from the head down to the trunk proceeds further to include the hip and the legs as well as the haptically perceived body support surface; by this, subjects yield a notion of support kinematics in space. As a consequence, spatial orientation is impaired by chronic vestibular deterioration only to the extent that the body support is moving in space, while it is unimpaired (determined by proprioception alone) during body motion with respect to a stationary support. Electronic Publication     

Blends of alkyloxy-substituted liquid-crystalline aromatic polyesters and copolyesters with poly(ethylene terephthalate)

Blends containing poly(ethylene terephthalate) (PET) and a series of alkyloxy laterally substituted liquid-crystalline copolyesters (HTO5-X series 1 ) in various ratios were prepared in the melt at 260°C by mechanical mixing. The visual and light microscopical appearance of the blends in the solid state and in the melt was found to be homogeneous for those blends which contained an aliphatic-rich HT05-X copolyester. The homogeneous appearance can be explained by a colloidal dispersion of the liquid-crystalline polymer (LCP) in PET. Obvious phase separation in the melt occurs slowly after long periods of time. Phase separation is forced by annealing at about 270°C, where a change of viscosity is observed, and by shearing the sample. Characterization of theblends by DSC experiments shows that the thermal behaviour of all blends is dominated by the phase transitions of PET and that the LC-low-phase of the HTO5-X copolyesters with a high degree of alkyloxy substitution is suppressed. The WAXS diffraction patterns of all blends contained an amorphous halo. For blends with low HTO5-X concentration, inner reflexions from the nematic sanidic phase, as exhibited by the HTO5-X copolyester, could be observed. For blends with higher HTO5-X copolyester concentration, characteristic reflexions from HTO5-X copolyester crystals could be observed. The number of X-ray reflexions of the crystalline LCP in the blend is reduced compared to that of the pure LCP.     

Heart-focused anxiety,illness beliefs,and behavioral impairment: Comparing healthy heart-anxious patients with cardiac and surgical inpatients

Psychological features and complaints of persons presenting to medical settings with heart-focused anxiety and noncardiac chest pain are poorly understood. Comparing 20 healthy heart-anxious patients to cardiac and surgical inpatients and nonpatient controls, we found that healthy heart-anxious patients (a) were as afraid of chest pain and heart palpitations as inpatients with heart disease, (b) were as incapacitated by symptoms and using medical services as much as both inpatient groups; and (c) reported higher levels of cardiac disease conviction, heart awareness, and behaviors designed to protect their heart than surgical patients and nonpatients. Compared to all other groups, healthy heart-anxious patients reported more panic and other anxiety disorders, hypochondriacal beliefs, physical symptoms, obsessive-compulsive concerns, and negative affect. Following a hyperventilation test, heart-anxious patients also indicated more distressing symptoms and thoughts, and felt less safe and in control than surgical patients and nonpatients. Results support efforts for a timely recognition, diagnosis, and behavioral treatment of persons with heart-focused anxiety.     

Immunolocalization of lamins and nuclear pore complex proteins by atomic force microscopy

The nuclear envelope functions as a selective barrier separating the nuclear from the cytosolic compartment. Nuclear pore complexes (NPCs) mediate nuclear import and export of macromolecules and, therefore, are potential regulators of gene expression. In this study we applied atomic force microscopy (AFM) to visualize the three dimensional (3D) structure of individual NPCs in the absence and presence of two different antibodies, one directed against a pore protein (gp62) and another directed against Xenopus lamin LIII, a component of the nuclear lamina, a filament meshwork localized on the nucleoplasmic side of the nuclear envelope (NE) adjacent to and interacting with NPCs. Using 12-nm gold-labelled secondary antibodies and transmission electron microscopy we could clearly localize the primary single anti-gp62 antibody on NPCs and the primary single anti-LIII antibody between NPCs. Using AFM, the secondary antibodies against anti-gp62 could be detected as particles 7 nm in height on the nucleoplasmic face of NPCs. The secondary antibodies against anti-LIII could be clearly identified between NPCs. The secondary antibodies, attached to a 12-nm colloidal gold particle and visualized on glass, revealed similar shapes and heights as found on NEs. According to the 3D images, the volume of a single gold particle conjugated with secondary antibodies was 10 203 nm³. This volume is equivalent to the volume of 38 IgG molecules associated with one individual gold particle. A similar volume of 11 987 nm³ was calculated from a model assuming that the 150-kDa IgG molecules perfectly cover the spherical gold particle. We conclude that AFM can be used for identifying antibodies or other macromolecules associated with biomembranes.     

Microglial Reaction in the Rat Cerebral Cortex Induced by Cortical Spreading Depression

The response of microglial cells to cortical spreading depression (CSD) was studied in rat brain by immunocytochemistry. CSD was elicited for one hour by the topical application of 4M potassium chloride solution and the microglial reaction examined immunocytochemically after 4, 16, 24 and 72 hours. CSD was sufficient to induce a microglial reaction throughout the cortex at 24 hours. Activated microglial cells furthermore showed a striking de-novo expression of major histocompatibility complex class II antigens. In contrast, no microglial reaction was observed in the cortex of sham-operated animals. This microglial reaction in response to CSD was not associated with histologically detectable neuronal damage. These results support the view that microglial cells are extremely sensitive to changes of the brain microenvironment. Their activation may be related to changes of ion homeostasis in the brain which are not sufficient to trigger neuronal injury.     

Der gitterfaktor des gaußschen parakristalls

By using so-called “characteristics”, the long-range distortion in Gaussian paracrystals may be described in a way which is independent of the lattice, provided distance and directional fluctuations between neighbouring lattice points are used. By a two-fold Fourier transform — similar to the approach of Warren and Averbach — the lattice factor, describing the interference effect of the Gaussian paracrystal, is found from the convolution of an ideal reciprocal lattice with a lattice-independent profile function. Threadlike “one-dimensional” Gaussian and ideal paracrystals are identical with each other. Making use of the two-fold Fourier transform, Hosemann's K-factor splits into isolated discs (“Scheibchen”) showing Lorentzian profiles. The profile function of two-and three-dimensional Gaussian paracrystals shows a Lorentzian-2/3 or a Lorentzian-2 profile, respectively. The different profiles are experimentally distinguishable when using a position-sensitive detector. Thus, based on experimental results, paracrystalline lattice distortions with Gaussian characteristics are detectable.