Immunologic characterization of isoforms of Car b 1 and Que a 1, the major hornbeam and oak pollen allergens.

Background: Birch pollen allergy is one of the most common causes of spring pollinosis often associated with hypersensitivity reactions to pollen of other Fagales species. Yet, only the major disease eliciting allergens of alder and hazel have been fully characterized. Therefore, the aim of this study was to perform cloning, expression and immunologic characterization of the Bet v 1 homologues from oak (Que a 1) and hornbeam (Car b 1).

Identification of B-cell epitopes of Bet v 1 involved in cross-reactivity with food allergens.

Background: The pollen-food syndrome (PFS) is an association of food allergies to fruits, nuts, and vegetables in patients with pollen allergy. Mal d 1, the major apple allergen, is one of the most commonly associated food allergens for birch pollen-allergic patients suffering from PFS. Although the reactions are due to cross-reactive IgE antibodies originally raised against pollen Bet v 1, not every Bet v 1-allergic patient develops clinical reactions towards apple.

Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria.

The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers.

Array-based profiling of ragweed and mugwort pollen allergens.

Background: Ragweed (Ambrosia artemisiifolia) and mugwort (Artemisia vulgaris) pollen is the main cause of allergic reactions in late summer and autumn. The differential diagnosis between ragweed and mugwort pollen allergy is a frequent problem encountered by allergologists in areas where both plants are present due to shared antigenic structures and overlapping flowering seasons.

Objective: To evaluate the sensitization pattern of weed allergic patients towards a large panel of purified allergens in the microarray format and by enzyme-linked immunosorbent assay (ELISA).

Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant alpha4beta3delta and alpha4beta3 GABA A receptors expressed in HEK cells.

General anesthetics, once thought to exert their effects through non-specific membrane effects, have highly specific ion channel targets that can silence neuronal populations in the nervous system, thereby causing unconsciousness and immobility, characteristic of general anesthesia. Inhibitory GABA(A) receptors (GABA(A)Rs), particularly highly GABA-sensitive extrasynaptic receptor subtypes that give rise to sustained inhibitory currents, are uniquely sensitive to GABA(A)R-active anesthetics. A prominent population of extrasynaptic GABA(A)Rs is made up of alpha4, beta2 or beta3, and delta subunits.

Molecular and immunological characterization of novel weed pollen pan-allergens.

Background: Pan-allergens like profilins, calcium-binding proteins (CBPs), and nonspecific lipid transfer proteins have been suggested as possible specific markers for multiple pollen sensitizations, and could be used to predict cross-sensitization/poly-sensitization to several pollen allergens. Therefore, the purification and characterization of cross-reacting allergens in pollen is an extremely important task towards correct allergy diagnosis.

Methods: New pan-allergens were identified by screening a ragweed pollen cDNA library with sera of patients allergic to mugwort pollen.

Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development?

Alcohol (ethanol, EtOH) has pleiotropic actions and induces a number of acute and long-term effects due to direct actions on alcohol targets, and effects of alcohol metabolites and metabolism. Many detrimental health consequences are due to EtOH metabolism and metabolites, in particular acetaldehyde, whose high reactivity leads to nonspecific chemical modifications of proteins and nucleic acids. Like acetaldehyde, alcohol has been widely considered a nonspecific drug, despite rather persuasive evidence implicating inhibitory GABA(A) receptors (GABA(A)Rs) in acute alcohol actions, for example, a GABA(A)R ligand, the imidazobenzodiazepine Ro15-4513 antagonizes many low-to-moderate dose alcohol actions in mammals.

The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification.

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control.

Clinically benign multiple sclerosis despite large T2 lesion load: can we explain this paradox?

Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 +/- 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 +/- 6 years) matched for disease duration.

Allergy multivaccines created by DNA shuffling of tree pollen allergens.

Background: The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment.

Objective: We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens.

Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition.

Based on the similarity of ethanol intoxication to the behavioral effects of drugs known to target gamma-aminobutyric acid type A (GABAA) receptors (GABARs), it has been suspected for decades that ethanol facilitates the activity of GABA. Even so, it has been surprisingly difficult to identify molecular targets of ethanol. Research conducted over the past several years suggests that a subclass of GABARs (those containing delta subunits) responds in a relevant concentration range to ethanol.

GABAA receptor subtypes: the "one glass of wine" receptors.

This review discusses evidence for and apparent controversy about, gamma-aminobutyric acid type A (GABAA) receptor (GABAAR) subtypes that mediate alcohol effects experienced during social drinking. GABAARs that contain the beta3 and delta subunits were shown to be enhanced by alcohol concentrations that mirror the concentration dependence of alcohol responses in humans. A mutation (alpha6R100Q) previously found in alcohol nontolerant rats in the cerebellar GABAAR alpha6 subunit is sufficient for increased alcohol-induced ataxia in rats homozygous for this mutation (alpha6-100QQ) and further increases alcohol sensitivity of tonic GABA currents (mediated by alpha6betadelta receptors) in cerebellar granule cells of alpha6-100QQ rats and in recombinant alpha6R100Qbeta3delta receptors.

Specific immunotherapy in pollen allergy.

Pollen allergy affects at least 10% of the global population, and up to one-third of the affected individuals displaying hay fever symptoms will later develop allergic asthma. The efficacy of allergen-specific immunotherapy (SIT) in seasonal allergic rhinitis has been confirmed in many clinical studies using grass, ragweed, and birch pollen extracts. SIT prevents the onset of new sensitizations to different allergens, and reduces the development of asthma in patients with allergic rhinitis caused by inhaled allergens, including pollen.

Methylation of serum DNA is an independent prognostic marker in colorectal cancer.

Purpose: Aberrant CpG island hypermethylation is a feature of a subgroup of colorectal cancers, which can be detected in the serum of affected patients. This study was designed to identify methylation targets with prognostic significance in the serum of patients with colorectal cancer.

Experimental Design: In a gene evaluation set consisting of sera from 24 patients with local colorectal cancers, 14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF, and hMLH1 were identified as potential serum DNA methylation markers.

A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.

Background: As conventional immunotherapy is less efficacious in patients with allergic multi-sensitivities compared with mono-sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi-sensitization with birch and grass pollen on the basis of mucosal tolerance induction.

Methods: The major birch pollen allergen Bet v 1 served as a scaffold for N- and C-terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli.

Depressive symptoms following herpes simplex encephalitis--an underestimated phenomenon?

Objective: In view of the herpes simplex virus' neurotropism for the limbic system and the temporal lobe, little is known about potential negative effects of this necrotizing encephalitis on affective functioning and health-related quality of life (HRQoL) after recovery. We therefore set out to explore an association between herpes simplex virus encephalitis (HSE) and both depressive symptoms and HRQoL.

Methods: A structured telephone interview was conducted in 26 subjects (F/M=10/16; age at follow-up, 49.

Low dose acute alcohol effects on GABA A receptor subtypes.

GABA(A) receptors (GABA(A)Rs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABA(A)R subtypes, nonsynaptic GABA(A)Rs have recently emerged as important regulators of neuronal excitability.

Low-dose alcohol actions on alpha4beta3delta GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513.

Although it is now more than two decades since it was first reported that the imidazobenzodiazepine Ro15-4513 reverses behavioral alcohol effects, the molecular target(s) of Ro15-4513 and the mechanism of alcohol antagonism remain elusive. Here, we show that Ro15-4513 blocks the alcohol enhancement on recombinant "extrasynaptic" alpha4/6beta3delta GABA(A) receptors at doses that do not reduce the GABA-induced Cl(-) current. At low ethanol concentrations (< or =30 mM), the Ro15-4513 antagonism is complete.

Modified recombinant allergens for safer immunotherapy.

Molecular cloning and recombinant production of allergens offered new perspectives for the increasing problem of allergies. A variety of preparations are being developed aiming to increase safety and improve efficacy of specific immunotherapy. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity, i.

Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors.

Although GABA(A) receptors have long been implicated in mediating ethanol (EtOH) actions, receptors containing the "nonsynaptic" delta subunit only recently have been shown to be uniquely sensitive to EtOH. Here, we show that delta subunit-containing receptors bind the imidazo-benzodiazepines (BZs) flumazenil and Ro15-4513 with high affinity (K(d) < 10 nM), contrary to the widely held belief that these receptors are insensitive to BZs. In immunopurified native cerebellar and recombinant delta subunit-containing receptors, binding of the alcohol antagonist [(3)H]Ro15-4513 is inhibited by low concentrations of EtOH (K(i) approximately 8 mM).

Basis of the gabamimetic profile of ethanol.

This article summarizes the proceedings of a symposium held at the 2005 Research Society on Alcoholism meeting. The initial presentation by Dr. Wallner provided evidence that selected GABA(A) receptors containing the delta subunit display sensitivity to low intoxicating ethanol concentrations and this sensitivity is further increased by a mutation in the cerebellar alpha6 subunit, found in alcohol-hypersensitive rats.

Contributions of the GABAA receptor alpha6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the alpha6 gene.

GABAA receptors (GABARs) are heteromultimeric proteins composed of five subunits. The specific subunit composition determines critical properties of a GABAR such as pharmacological sensitivities and whether the receptor contributes to synaptic or extrasynaptic forms of inhibition. Classically, synaptic but not extrasynaptic GABARs are thought to respond to benzodiazepines, whereas the reverse has been suggested for ethanol.

[Peritoneal dialysis in patients with polycystic kidney disease].

In Austria, patients with end-stage renal disease caused by polycystic kidney disease are less frequently treated with peritoneal dialysis (PD) than patients with noncystic renal diseases (6% versus 8%). In contrast, the United States renal data system reports that more than one fifth of patients with polycystic kidney disease choose PD as their initial form of renal replacement therapy. The reasons for this difference are unknown.