No meditation-related changes in the auditory N1 during first-time meditation.

Recent studies link meditation expertise with enhanced low-level attention, measured through auditory event-related potentials (ERPs). In this study, we tested the reliability and validity of a recent finding that the N1 ERP in first-time meditators is smaller during meditation than non-meditation - an effect not present in long-term meditators. In the first experiment, we replicated the finding in first-time meditators. In two subsequent experiments, we discovered that this finding was not due to stimulus-related instructions, but was explained by an effect of the order of conditions. Extended exposure to the same tones has been linked with N1 decrement in other studies, and may explain N1 decrement across our two conditions. We give examples of existing meditation and ERP studies that may include similar condition order effects. The role of condition order among first-time meditators in this study indicates the importance of counterbalancing meditation and non-mediation conditions in meditation studies that use event-related potentials.

Electroweak Corrections to pp→µ

The first complete calculation of the next-to-leading-order electroweak corrections to four-lepton production at the LHC is presented, where all off-shell effects of intermediate Z bosons and photons are taken into account. Focusing on the mixed final state µ^{+}µ^{-}e^{+}e^{-}, we study differential cross sections that are particularly interesting for Higgs boson analyses. The electroweak corrections are divided into photonic and purely weak corrections. The former exhibit patterns familiar from similar W- or Z-boson production processes with very large radiative tails near resonances and kinematical shoulders. The weak corrections are of the generic size of 5% and show interesting variations, in particular, a sign change between the regions of resonant Z-pair production and the Higgs signal.

Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina.

Gliosis of retinal Müller glial cells may have both beneficial and detrimental effects on neurons. To investigate the role of purinergic signaling in ischemia-induced reactive gliosis, transient retinal ischemia was evoked by elevation of the intraocular pressure in wild-type (Wt) mice and in mice deficient in the glia-specific nucleotide receptor P2Y1 (P2Y1 receptor-deficient (P2Y1R-KO)). While control retinae of P2Y1R-KO mice displayed reduced cell numbers in the ganglion cell and inner nuclear layers, ischemia induced apoptotic death of cells in all retinal layers in both, Wt and P2Y1R-KO mice, but the damage especially on photoreceptors was more pronounced in retinae of P2Y1R-KO mice. In contrast, gene expression profiling and histological data suggest an increased survival of amacrine cells in the postischemic retina of P2Y1R-KO mice. Interestingly, measuring the ischemia-induced downregulation of inwardly rectifying potassium channel (Kir)-mediated K(+) currents as an indicator, reactive Müller cell gliosis was found to be weaker in P2Y1R-KO (current amplitude decreased by 18%) than in Wt mice (decrease by 68%). The inner retina harbors those neurons generating action potentials, which strongly rely on an intact ion homeostasis. This may explain why especially these cells appear to benefit from the preserved Kir4.1 expression in Müller cells, which should allow them to keep up their function in the context of spatial buffering of potassium. Especially under ischemic conditions, maintenance of this Müller cell function may dampen cytotoxic neuronal hyperexcitation and subsequent neuronal cell loss. In sum, we found that purinergic signaling modulates the gliotic activation pattern of Müller glia and lack of P2Y1 has janus-faced effects. In the end, the differential effects of a disrupted P2Y1 signaling onto neuronal survival in the ischemic retina call the putative therapeutical use of P2Y1-antagonists into question.

Unusual vascular focal high-grade arterial stenoses in a young woman with systemic lupus erythematosus and secondary antiphospholipid syndrome.

We report the case of a 28-year old woman with an unusual presentation of peripheral arterial occlusive disease clinically characterized by intermittent claudication and bilateral, focal stenoses of the iliac arteries without signs of atherosclerosis in other vascular beds. The successful percutaneous intervention is described in detail and pathogenetic aspects of the disease are discussed.

Partial reconstitution of cutaneous microvessels in long-term survivors after allogeneic bone marrow transplantation.

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in acute and chronic disease. Immune-mediated vessel attack and subsequent microvessel loss have been observed in skin of patients with chronic GVHD. OBJECTIVES: To test whether long-term survivors (LTS) after allogeneic HSCT without cutaneous GVHD show signs of persistent vascular remodeling. METHODS: Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a median follow-up of 17 years (range 11-26). Five were currently classified as having chronic GVHD other than skin involvement. RESULTS: LTS showed no significant difference in median microvessel density and relative vessel size distribution pattern compared to healthy controls. Past experience of GVHD and current status of chronic GVHD other than skin involvement had no impact on vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic type and patients with lichen sclerosus have significant microvessel loss in the upper dermis. CONCLUSION: The complex therapy of allogeneic HSCT had no sustained effect on the microvascular architecture of LTS when clinicopathological evidence of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic GVHD recovers completely after resolution of chronic cutaneous GVHD.

The nonlinear Fano effect.

The Fano effect is ubiquitous in the spectroscopy of, for instance, atoms, bulk solids and semiconductor heterostructures. It arises when quantum interference takes place between two competing optical pathways, one connecting the energy ground state and an excited discrete state, the other connecting the ground state with a continuum of energy states. The nature of the interference changes rapidly as a function of energy, giving rise to characteristically asymmetric lineshapes. The Fano effect is particularly important in the interpretation of electronic transport and optical spectra in semiconductors. Whereas Fano's original theory applies to the linear regime at low power, at higher power a laser field strongly admixes the states and the physics becomes rich, leading, for example, to a remarkable interplay of coherent nonlinear transitions. Despite the general importance of Fano physics, this nonlinear regime has received very little attention experimentally, presumably because the classic autoionization processes, the original test-bed of Fano's ideas, occur in an inconvenient spectral region, the deep ultraviolet. Here we report experiments that access the nonlinear Fano regime by using semiconductor quantum dots, which allow both the continuum states to be engineered and the energies to be rescaled to the near infrared. We measure the absorption cross-section of a single quantum dot and discover clear Fano resonances that we can tune with the device design or even in situ with a voltage bias. In parallel, we develop a nonlinear theory applicable to solid-state systems with fast relaxation of carriers. In the nonlinear regime, the visibility of the Fano quantum interferences increases dramatically, affording a sensitive probe of continuum coupling. This could be a unique method to detect weak couplings of a two-level quantum system (qubits), which should ideally be decoupled from all other states.

Selective loss of extracellular matrix proteins is linked to biophysical properties of varicose veins assessed by ultrasonography.

BACKGROUND: Dilatation and enhanced distensibility are specific biophysical properties of varicose veins. Both can be assessed by ultrasonography. The aim of this study was to analyse correlations between the vein wall protein content and these two biophysical properties of varicose veins. METHODS: Twenty-seven patients having surgery for varicose veins and six control patients with normal veins undergoing arterial bypass surgery were examined clinically and with ultrasonography the day before surgery. Fifty-two varicose and six control vein rings were harvested and analysed histopathologically and morphometrically; vascular tissue microarrays incorporated 116 vein wall sectors. RESULTS: Elastin loss in the adventitia (P = 0.010) and reduction of type III collagen in the intima and media (P = 0.004) were observed in varicose veins. Elastin loss correlated negatively with vein diameter at rest (P = 0.005), whereas loss of type III collagen in the intima correlated negatively with the increase in vein diameter at the Valsalva manoeuvre (P < 0.001). CONCLUSION: Loss of elastin and type III collagen occurs in varicose veins and can be assessed with ultrasonography in vivo by measuring vein diameter and distensibility.

[Percutaneous transluminal coronary angioplasty--treatment of symptoms or treatment of cause?]. / Perkutane transluminale Angioplastie--symptomatische oder kausale Therapie?

Percutaneous transluminal angioplasty is a highly efficient therapy of an acute arterial occlusion, particularly in the coronary system. Arteriosclerosis is the most common cause of an acute occlusion of a coronary artery. However, arteriosclerosis is not only limited to the coronary circulation but is a panarterial disease. The molecular characterization of the underlying disease process and, consecutively, the individual typing of arteriosclerosis forms the basis of a targeted, personalized drug therapy. First approaches of such targeted therapies to treat arterioscleroses are currently tested in randomized, controlled trials.

Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease.

Cytotoxic T lymphocytes (CTLs) are important effector cells of graft-versus-host disease (GVHD) and vascular endothelial cells are target cells of allospecific CTL. A combined assessment of T-cell activation and endothelial injury should result in a specific and sensitive test for GVHD. We examined circulating T lymphocytes for effector molecules involved in CTL-mediated endothelial injury. We analyzed CD4 and CD8 T lymphocytes of 24 long-term survivors of allogeneic stem cell transplantation with or without GVHD, and nine healthy, age-matched controls for signs of CTL activation and endothelial injury. IFN-gamma transcript levels in CD8 T cells were significantly elevated in SCT recipients with GVHD compared to patients without GVHD (767 CD3epsilon units/T cell (376-2050) vs 211 CD3epsilon units/T cell (159-274), P=0.01). Fas ligand transcript levels in CD4 T cells were significantly elevated in SCT recipients without GVHD compared to patients with GVHD (20 CD3epsilon units/T cell (0-78) vs 0 CD3epsilon units/T cell (0-0), P=0.01). Von Willebrand factor plasma levels were high in patients with GVHD, but normal in patients without GVHD (209 (186-254) vs 120 (100-141), P=0.0005). This assessment of T-cell activation and endothelial injury results in a sensitive and specific test to identify patients with active chronic GVHD.

Kir subfamily in frog retina: specific spatial distribution of Kir 6.1 in glial (Müller) cells.

We show by immunocytochemistry in frog retina that most members of the Kir subfamily are expressed in specific neuronal compartments. However, Kir 6.1, the pore-forming subunit of K(ATP) channels, is expressed exclusively in glial Müller cells. Müller cell endfeet display strong Kir 6.1 immunolabel throughout the retina, whereas the somata are labeled only in the retinal periphery. This spatial pattern is similar to that of Kir 4.1, of the ratio of inward to outward K+ currents, and of spermine/spermidine immunoreactivity. We suggest that the co-expression of Kir 4.1 and Kir 6.1 subunits may enable the cells to maintain their high K+ conductance and hyperpolarized membrane potentials both at high ATP levels (Kir 4.1) and during ATP deficiency (Kir 6.1).

Vascular endothelium: checkpoint for inflammation and immunity.

Vascular endothelial cells play a threefold role in the interaction with leukocytes. First, they are gatekeepers in leukocyte recruitment to inflammatory foci and lymphocyte homing to secondary lymphoid organs. Second, they modulate leukocyte activation. Finally, they are targets of leukocyte-derived molecules, resulting either in endothelial cell activation or death.

Facilitation of artificial retinal detachment for macular translocation surgery tested in rabbit.

PURPOSE: For macular translocation surgery, the native attached retina has to be detached either locally or completely. Although different surgical techniques are used, there is a general search for supporting procedures that facilitate and accelerate the retinal detachment. METHODS: Pars plana vitrectomies were performed in pigmented rabbits. In all experimental groups, a local retinal detachment was created by infusing the test solution with a thin glass micropipette attached to a glass syringe. In control animals a standard balanced salt solution was used at room temperature, in combination with a standard vitrectomy light source. In two test groups, a calcium- and magnesium-free solution was used for the vitrectomy, under illumination by a standard light source in group I (solution at room temperature) and group II (solution heated up to body temperature). In group III the rabbits were dark-adapted for half an hour, and then, during surgery, a red filter was used in front of the light source (standard balanced salt solution at room temperature). After the rabbits were killed at the end of surgery, the adherence of the retinal pigment epithelium (RPE) to the neural retina in the detachment area was quantified microscopically, and the morphologic integrity of the detached retinal tissue was examined by light and electron microscopy. No electrophysiology was performed. RESULTS: In all four groups, it was possible to detach the retina. The maximum adherence of the RPE cells to the neural retina was observed in the control group. Virtually no decrease in adherence was found in test group II (36 degrees C solution without calcium and magnesium), whereas a significant decrease was seen in both group I (calcium- and magnesium-free solution at room temperature) and group III (dark adaptation-red light technique; standard balanced salt solution at room temperature). In none of the experimental groups was any obvious damage of the retinal structure observed, even after exposure to the test solutions for 60 minutes. CONCLUSIONS: Both dark adaptation (red illumination) and the use of a calcium chloride- and magnesium chloride-free solution (at room temperature) can facilitate retinal detachment in macular translocation surgery. Both techniques are proposed as a gentle support for the operation, because they protect an intact RPE cell layer and do not cause retinal damage at the ultrastructural level.

Involvement of calcium-activated potassium channels in the regulation of DNA synthesis in cultured Müller glial cells.

PURPOSE: To determine the involvement of Ca(2+)-activated K(+) channels of big conductance (BK) and of Ca(2+) channels in the regulation of DNA synthesis in cultured guinea pig Müller cells. DNA synthesis was stimulated by elevated extracellular potassium, by serum, or by epidermal growth factor. METHODS: Dissociated retinas from guinea pigs were cultured for 8 days. Just before confluence was achieved, the cultures were treated with the test substances in serum-free or serum-containing media. The rates of DNA synthesis were assessed by a quantitative bromodeoxyuridine immunoassay. The intracellular Ca(2+) concentration was measured by the fura-2 fluorescence technique. RESULTS: Blocking the BK channels with tetraethylammonium or by iberiotoxin had no effect at normal extracellular K(+) (5.8 mM) but decreased the rate of DNA synthesis at higher extracellular K(+) (10 or 25 mM). Epidermal growth factor-induced DNA synthesis was decreased by block of BK channels or by application of the Ca(2+) channel blockers nimodipine and flunarizine. Application of epidermal growth factor elevated the intracellular Ca(2+) concentration of cultured Müller cells. This elevation was diminished by co-application of iberiotoxin or of flunarizine. CONCLUSIONS: The activity of BK channels is necessary for elevated DNA synthesis in Müller cells when their membranes are depolarized and/or when the Ca(2+) influx into Müller cells is increased by growth factors. BK channels may contribute to the maintenance of DNA synthesis by increasing mitogen-induced increase in intracellular Ca(2+) concentration.

Combined chemoradiotherapy with daily low-dose cisplatin in locally advanced inoperable non-small cell lung cancer.

Sixty-one consecutive patients with locally advanced inoperable non-small-cell lung cancer were treated with chemoradiation with 60 Gy and concomitant daily low-dose cisplatin (6 mg/m(2)) in a single uninterrupted course. Toxicity was mild, 80% of patients were treated as outpatients. The median survival of 70 weeks compares favorably to the literature.

Age- and disease-related changes of calcium channel-mediated currents in human Müller glial cells.

PURPOSE: To determine whether the expression of voltage-gated Ca2+ channels in human Müller glial cells changes during normal aging and in cells from patients with proliferative vitreoretinopathy (PVR). METHODS: Müller cells were enzymatically isolated from retinas of healthy donors and from excised retinal pieces of patients with PVR, and the whole-cell, voltage-clamp technique was used to characterize the current densities of transient, low-voltage-activated calcium channels and of sustained. high-voltage-activated calcium channels, respectively. To obtain maximal currents through both channel types, Na+ ions were used as the charge carrier. RESULTS: During normal aging, Müller cells developed a hypertrophy, as indicated by an increase of the cell membrane capacitance. The mean membrane capacitance of cells from aged donors (> or = 60 years old) was elevated by 25% compared with cells from younger donors. The hypertrophy was not accompanied by a changed density of low-voltage-activated currents, whereas the density of the high-voltage-activated currents was enhanced by 76%. The density of the high-voltage-activated currents increased in correlation with the increase of the cell membrane capacitance and with the age of the donors. In the case of PVR, Müller cells displayed a strong hypertrophy accompanied by a downregulation of both current types by approximately 65%. CONCLUSIONS: Both normal aging and PVR cause a gliotic reactivity of human Müller cells, as indicated by their hypertrophy. The type of reactivity, however, differs between the two conditions. Normal aging is accompanied by an increased expression of voltage-gated Ca2+ channels, whereas in PVR Ca2+ channel expression is decreased.

P2X7 receptors in Müller glial cells from the human retina.

ATP has been shown to be an important extracellular signaling molecule. There are two subgroups of receptors for ATP (and other purines and pyrimidines): the ionotropic P2X and the G-protein-coupled P2Y receptors. Different subtypes of these receptors have been identified by molecular biology, but little is known about their functional properties in the nervous system. Here we present data for the existence of P2 receptors in Müller (glial) cells of the human retina. The cells were studied by immunocytochemistry, electrophysiology, Ca(2+)-microfluorimetry, and molecular biology. They displayed both P2Y and P2X receptors. Freshly enzymatically isolated cells were used throughout the study. Although the [Ca(2+)](i) response to ATP was dominated by release from intracellular stores, there is multiple evidence that the ATP-induced membrane currents were caused by an activation of P2X(7) receptors. Immunocytochemistry and single-cell RT-PCR revealed the expression of P2X(7) receptors by Müller cells. In patch-clamp studies, we found that (1) benzoyl-benzoyl ATP (BzATP) was the most effective agonist to evoke large inward currents and (2) the currents were abolished by P2X antagonists; however, (3) long-lasting application of BzATP did not cause an opening of large pores in addition to the cationic channels. By microfluorimetry it was shown that the P2X receptors mediated a Ca(2+) influx that contributed a small component to the total [Ca(2+)](i) response. Activation of P2X receptors may modulate the uptake of neurotransmitters from the extracellular space by Müller cells in the retina.

Müller glial cells in anuran retina.

Whereas in the brain, the activity of the neurons is supported by several types of glial cells such as astrocytes, oligodendrocytes, and ependymal cells, the retina (evolving from the brain during ontogenesis) contains only one type of macroglial cell, the Müller (radial glial) cells, in most vertebrates including the anurans. These cells span the entire thickness of the tissue, and thereby contact and ensheath virtually every type of neuronal cell body and process. This intimate topographical relationship is reflected by a multitude of functional interactions between retinal neurons and Müller glial cells. Müller cells are the principal stores of retinal glycogen, and are thought to fuel retinal neurons with substrate (lactate/pyruvate) for their oxidative metabolism. Furthermore, Müller cells are involved in the control and homeostasis of many constituents of the extracellular space, such as potassium and perhaps other ions, signaling molecules, and of the extracellular pH. They also seem to play important roles in recycling mechanisms of photopigment molecules and neurotransmitter molecules such as glutamate and GABA. By containing the main retinal stores of glutathione, Müller cells may protect retinal neurons against free radicals. Moreover, Müller cells express receptors for many neuroactive substances, and may also release such substances to their neighbouring neurons. Thus, Müller cells exert many functions crucial for signal processing in the normal retina. Moreover, Müller cells change their properties in cases of retinal disease and injury, and may either support the survival of neuronal cells or accelerate the progress of neuronal degeneration.

Na(+) currents through Ca(2+) channels in human retinal glial (Müller) cells.

PURPOSE: To detect the presence of voltage-gated Ca(2+) channels in the plasma membranes of freshly isolated Müller glial cells from the human retina and their modulation by GABA(B) receptor agonists. METHODS: Whole cell voltage-clamp recordings were made to study Ca( 2+), Ba(2+), and Na(+) currents through voltage-gated Ca(2+) channels. RESULTS: The vast majority of the investigated cells displayed no resolvable currents through Ca(2+) channels when Ca(2+) ions (2 mM) were present in the extracellular solution. Small-amplitude inwardly directed currents ( approximately 0.6 pA/pF) were detected when Ba(2+) ions (20 mM) were used as charge carrier. However, when Na(+) ions were used as charge carrier in divalent cation-free external solution, currents of large amplitudes ( approximately 7.5 pA/pF) through voltage-gated Ca(2+) channels were detected. Human Müller cells displayed currents through both transient, low voltage-activated Ca(2+) channels and long-lasting, high voltage-activated channels. The Na(+) fluxes through low voltage-activated Ca( 2+) channels were inhibited in a voltage-independent manner in the presence of GABA(B) receptor agonists. CONCLUSIONS: Human Müller glial cells express different kinds of voltage-gated Ca(2+) channels in their plasma membranes that can be activated only under certain physiological or pathophysiological conditions. The record of Na(+) fluxes in divalent cation-free solutions may be a technique to detect the presence of "hidden" voltage-gated Ca(2+) channels in Müller glial cells.

Spatial distribution of spermine/spermidine content and K(+)-current rectification in frog retinal glial (Müller) cells.

Previous studies in retinal glial (Müller) cells have suggested that (1) the dominant membrane currents are mediated by K(+) inward-rectifier (Kir) channels (Newman and Reichenbach, Trends Neurosci 19:307-312, 1996), and (2) rectification of these Kir channels is due largely to a block of outward currents by endogenous polyamines such as spermine/spermidine (SPM/SPD) (Lopatin et al., Nature 372:366-369, 1994). In frog Müller cells, the degree of rectification of Kir-mediated currents is significantly higher in the endfoot than in the somatic membrane (Skatchkov et al., Glia 27:171-181, 1999). This article shows that in these cells there is a topographical correlation between the local cytoplasmic SPM/SPD immunoreactivity and the ratio of inward to outward K(+) currents through the surrounding membrane area. Throughout the retina, Müller cell endfeet display a high SPM/SPD immunolabel (assessed by densitometry) and a large inward rectification of K(+) currents, as measured by the ratio of inward to outward current produced by step changes in [K(+)](o). In the retinal periphery, Müller cell somata are characterized by roughly one-half of the SPM/SPD immunoreactivity and K(+)-current rectification as the corresponding endfeet. In the retinal center, Müller cell somata are virtually devoid of both SPM/SPD immunolabel and K(+)-current inward rectification. Comparing one region of the retina with another, we find an exponential correlation between the local K(+) rectification and the local SPM/SPD content. This finding suggests that the degree of inward rectification in a given membrane area is determined by the local cytoplasmic polyamine concentration.