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Biomedical subjects

S Kraft

Publications and source records attributed to S Kraft.

At least 19 recordsLinked to original sources

Impulsiveness in obsessive-compulsive disorder: results from a family study.

OBJECTIVE: Although obsessive-compulsive disorder (OCD) is usually conceptualized as an anxiety disorder some studies suggested it to be a deficit of impulse control. The purpose of this study was to assess impulsiveness in OCD families and compare it to control families. METHOD: Seventy cases and their 139 relatives were compared with 70 controls and their 134 relatives from a German family study on OCD (German Epidemiologic Network for OCD Studies). All subjects were interviewed and diagnosed according DSM-IV criteria and were administered the Barratt Impulsiveness Scale (BIS) and PADUA-Inventory to assess obsessive-compulsive symptoms. RESULTS: OCD subjects had significantly higher scores of cognitive impulsiveness. However, first-degree relatives of OCD cases and of controls had comparable BIS-11 scores. Significant associations of aggressive obsessions and checking with cognitive impulsiveness were found. CONCLUSION: OCD is a severe mental disorder that is characterized by a lack of cognitive inhibition. However, impulsiveness does not represent a familial trait in families of OCD subjects.

Adult↗

CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.

Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane-resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.

Animals↗

Referrals for movement disorder surgery: under-representation of females and reasons for refusal.

OBJECTIVE: Referral of movement disorder patients for deep brain stimulation surgery was examined to determine whether referred patients were representative of gender proportions in our population, and reasons why patients do not proceed to surgery. METHODS: Demographic information on referrals to the surgical program was retrospectively reviewed from our database and from a detailed chart review. RESULTS: Although almost equal numbers of movement disorder patients are male and female, of the 91 patients referred for surgery, only 31% were female. Sixty-one percent of referred patients did not undergo surgery. Of these, the majority were denied for medical reasons, including cognitive decline (21%), psychiatric concerns (5%) and neurological reasons (42%). CONCLUSIONS: Almost one-third of patients referred for movement disorder surgery were denied for medical reasons. This underscores the importance of evaluation of all potential patients by a multidisiplinary team to fully assess suitablity for stereotactic surgery. Interestingly, women were under-represented in those referred. In order that all appropriate patients have the opportunity to consider surgery, education of both physicians and patients, and different strategies to approach females regarding surgery may allow more patients to benefit from this treatment.

Deep Brain Stimulation↗

Diffraction of a Bose-Einstein condensate from a magnetic lattice on a microchip.

We experimentally study the diffraction of a Bose-Einstein condensate from a magnetic lattice, realized by a set of 372 parallel gold conductors which are microfabricated on a silicon substrate. The conductors generate a periodic potential for the atoms with a lattice constant of 4 microm. After exposing the condensate to the lattice for several milliseconds we observe diffraction up to fifth order by standard time of flight imaging techniques. The experimental data can be quantitatively interpreted with a simple phase imprinting model. The demonstrated diffraction grating offers promising perspectives for the construction of an integrated atom interferometer.

Journal Article↗

Dementia of frontal lobe type in Kennedy's disease.

The pathomorphological correlate of Kennedy's disease (KD) is a degeneration of spinal and bulbar alpha-motor neurons. The disease is caused by a CAG repeat expansion in the first exon of the X-chromosomal androgene receptor gene. Contrary to the common belief that cognitive disorders in motor neuron diseases (MND) are either rare or only mild, there is now an increasing number of case reports on dementia in amyotrophic lateral sclerosis (ALS). In ALS, dementia of the frontal lobe type (frontotemporal dementia, FTD) seems to be the characteristic pattern. However, in KD cognitive dysfunction has not been studied systematically. Here we present a case with clinical characteristics of FTD in a patient with genetically confirmed KD. It remains speculative whether there is an association between KD and FTD comparable to a genetic linkage between ALS and FTD, which has been proposed in recent years. However, we suggest that cognitive dysfunction may be more common in KD than reported until today.

Adult↗

Limited reliability of E-cadherin as a specific marker for in vitro-generated Langerhans cells.

Langerhans cells (LC) are a unique population of dendritic cells (DC) found in the epidermis where they can be identified by the expression of CD1a, E-cadherin and cytoplasmic Birbeck granules (BG) as their hallmark. Over the past years many techniques have been described to generate LC in vitro from either monocytes or CD34(+) hematopoietic cell progenitors. Antibodies against Lag and Langerin (two epitopes associated with BG) and E-cadherin (a Ca(2+)-dependent homophilic adhesion molecule) have been used to detect in vitro-generated LC. In this study we investigated whether the expression of E-cadherin on in vitro-generated CD1a(+) from either CD34(+) cells or monocytes is able to discriminate LC from other DC. Our results demonstrate that E-cadherin alone is not a reliable marker to specifically identify in vitro-generated LC.

Antigens, CD↗

Nonlinear dynamics of a Bose-Einstein condensate in a magnetic waveguide.

We have studied the internal and external dynamics of a Bose-Einstein condensate in an anharmonic magnetic waveguide. An oscillating condensate experiences a strong coupling between the center of mass motion and the internal collective modes. Because of the anharmonicity of the magnetic potential, not only the center of mass motion shows harmonic frequency generation, but also the internal dynamics exhibit nonlinear frequency mixing. Thereby, the condensate shows shape oscillations with an extremely large change in the aspect ratio of up to a factor of 10. We describe the data with a theoretical model to high accuracy. For strong excitations we test the experimental data for indications of a chaotic behavior.

Journal Article↗

Meconium peritonitis and pseudo-cyst formation: prenatal diagnosis and post-natal course.

OBJECTIVES: Intra-uterine bowel perforation can occur secondary to a variety of abnormalities and cause sterile peritonitis in the fetus (generalised = type I). If sealing of the perforation does not take place, a thick-walled pseudo-cyst can form (type II). METHODS: Over a 12-year period, 21 616 pregnancies were screened for gastro-intestinal malformations using prenatal ultrasound. We identified 1077 cases suspicious of surgically correctable malformations. Post-natal diagnoses and outcome were worked up retrospectively. RESULT: We found 96 fetuses with suspected gastro-intestinal malformations. Prenatal bowel perforation with meconium peritonitis was confirmed in 11 cases. In 5 of these 11, the correct diagnosis had been predicted prenatally. One child presented as a fetal and neonatal emergency (case report). Ten of the eleven infants were operated on during their first day of life. Intra-operative findings were atresia (n = 4), meconium ileus (n = 6) and no obvious cause (n = 1). Two children suffered fatal complications. CONCLUSION: Meconium peritonitis and meconium pseudo-cysts as its special manifestation are assessable by prenatal diagnosis but present in different ways. They can present as fetal ascites or echogenic bowel and cause fetal or neonatal distress, requiring close observation and highly specialised care.

Adult↗

[A rare location for extratruncular vascular malformation].

We report on an undefined tumor of the right ulnar side of the elbow in a 15-year-old boy. The clinical examination showed painful swelling in the area of the ulnar nerve at the right elbow as well as sensory and motor deficits of the right hand corresponding to distribution of the ulnar nerve. Ultrasound examination and magnetic resonance imaging showed a tumor along the nerve. Subsequent surgical therapy included tumor decompression by division of the fascia. The histological examination demonstrated a capillary hemangioma that infiltrated the ulnar nerve.After surgery, oral glucocorticoid therapy with cortisone (5 mg/kg per day) was administered over a period of 4 weeks, alternating between 1 week of therapy and 1 week without medication. The result of this combined therapy was a rapid diminution of the tumor and an almost complete restitution of the neural function.

Adolescent↗

The central role of FcepsilonRI in allergy.

The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, plays a central role in the initiation and control of atopic allergic inflammation. On mast cells and basophils, the function of the receptor is well known and constitutes cellular degranulation and the release of various mediators. FcepsilonRI on antigen-presenting cells (APCs), however, does not lead to degranulation of preformed granula, but has different functions: signal transduction pathways like the activation of NF-kappaB are initiated to induce inflammatory cytokine gene expression. In addition, FcepsilonRI on APCs acts as an allergen-focusing structure and can efficiently amplify allergen presentation in an IgE-dependent manner. Recently, we and others have gained new insight into the regulation and function of FcepsilonRI on APCs, which has shed new light on the modulating effects of the immune system in atopic inflammation.

Animals↗

Sympathetic cooling with two atomic species in an optical trap.

We simultaneously trap ultracold lithium and cesium atoms in an optical dipole trap formed by the focus of a CO2 laser and study the exchange of thermal energy between the gases. The optically cooled cesium gas efficiently decreases the temperature of the lithium gas through sympathetic cooling. Equilibrium temperatures down to 25 microK have been reached. The measured cross section for thermalizing 133Cs-7Li collisions is 8 x 10(-12) cm(2), for both species unpolarized in their lowest hyperfine ground state. Besides thermalization, we observe evaporation of lithium purely through elastic cesium-lithium collisions (sympathetic evaporation).

Journal Article↗

Land-use dynamics in a southern Illinois (USA) watershed.

The Cache River of southernmost Illinois is used as a case study for developing and demonstrating an approach to quantitatively link (1) national agricultural policy and global agricultural markets, (2) landowner's decisions on land use, (3) spatial patterns of land use at a watershed scale, and (4) hydrologic impacts, thus providing a basis to predict, under a certain set of circumstances, the environmental consequences of economic and political decisions made at larger spatial scales. The heart of the analysis is an estimation, using logistic regression, of the affect of crop prices and Conservation Reserve Program (CRP) rental rates on farmland owner's decisions whether to reenroll in the CRP or return to crop production. This analysis shows that reasonable ranges for crop prices (80%-150% of 1985-1995 values) and CRP rental rates (0-125% of 1985-1995 rates) result in a range of 3%-92% of CRP lands being returned to crop production, with crop prices having a slightly greater effect than CRP rental rates. Four crop price/CRP rental rate scenarios are used to display resulting land-use patterns, and their effect on sediment loads, a critical environmental quality parameter in this case, using the agricultural non point source (AGNPS) model. These scenarios demonstrate the importance of spatial pattern of land uses on hydrological and ecological processes within watersheds. The approach developed can be adapted for use by local governments and watershed associations whose goals are to improve watershed resources and environmental quality.

Agriculture↗

IgE receptors.

IgE receptors are implicated as important components of the immunological pathway in allergic and inflammatory diseases. Recent investigations have begun to unravel the structure, signal transduction and function of IgE receptors from different cell types in rodent and human systems. Studies of the mechanisms involved might provide opportunities for therapeutic intervention strategies in the treatment of allergic and hypersensitivity reactions.

Animals↗

Human epidermal Langerhans' cells are targets for the immunosuppressive macrolide tacrolimus (FK506).

BACKGROUND: The immunosuppressive macrolide tacrolimus (FK506) has been shown to inhibit allergic contact dermatitis in animal models as well as in human beings. More recently, successful treatment of atopic dermatitis with an ointment containing tacrolimus has been reported. OBJECTIVES: We explored the effects of this compound on epidermal Langerhans' cells (LCs), which are known to play an important pathophysiologic role in inflammatory skin diseases. METHODS: The expression of the intracellular FK506 binding protein (FKBP12) was monitored on freshly isolated and cultured epidermal LCs. Phenotyping and functional exploration of LCs treated with different concentrations of tacrolimus and beta-methasone valerate (betaMv) were performed. RESULTS: FKBP12 is expressed in freshly isolated LCs but is lost while they are maturating into mature dendritic cells. Tacrolimus inhibited the expression of IL-2R (CD25) and of the costimulatory molecules CD80 (B7.1) and CD40. Expression of MHC class I and II was also affected, whereas CD86 (B7.2) expression was not altered. In contrast, betaMv strongly increased the expression of CD25. Paradoxically, while decreasing CD40 and MHC class I expression, betaMv significantly increased the expression of MHC class II, CD80, and CD86 on cultured LCs but impaired their allostimulatory activity. Tacrolimus was about 100 times more potent than betaMv at inhibiting LC stimulatory function. CONCLUSION: Tacrolimus can exert immunopharmacologic alterations on LCs, which may account, at least in part, for the therapeutic effect of this compound in eczematous skin diseases.

Administration, Topical↗

Standardized extracts from Chinese herbs induce IL-10 production in human monocyte-derived dendritic cells and alter their differentiation in vitro.

BACKGROUND: The efficacy of traditional Chinese medicine (TCM) as a treatment for atopic dermatitis has been evaluated in clinical trials. Until now, the underlying mechanism of this treatment has remained completely elusive; this is particularly true of its putative effects on dendritic cells (DCs), which might play a pivotal role in the disease. OBJECTIVE: We investigated the influence of a standardized extract from 10 Chinese herbs that was successfully used in clinical trials on the generation of monocyte-derived DCs from atopic donors. METHODS: Detailed phenotypic and functional exploration of DCs generated in the presence of IL-4 and GM-CSF and treated with different concentrations of TCM or a placebo control was performed. RESULTS: TCM profoundly affected the morphology and phenotype of the developing DCs. They lost their typical dendritic morphology and decreased their expression of CD1a as well as the low-affinity IgE receptor CD23. Most importantly, TCM-exposed DCs exhibited a diminished stimulatory activity toward autologous antigen-specific and allogeneic T cells while secreting high amounts of IL-10. CONCLUSION: TCM induces immunopharmacologic alterations on DCs from atopic donors in vitro. These alterations might account, at least in part, for the therapeutic effect of this treatment in AD in vivo.

Dendritic Cells↗

Fc epsilon ri-mediated activation of transcription factors in antigen-presenting cells.

Professional antigen-presenting cells (APC) such as monocytes and dendritic cells (DC) bearing high-affinity IgE receptors (Fc epsilon RI) efficiently present IgE-bound antigens to T cells. Fc epsilon RI expression is upregulated on APC from atopic donors, especially in inflamed tissues. These data suggest a pathophysiological concept of an IgE-mediated delayed-type hypersensitivity reaction in atopic diseases. However, Fc epsilon RI ligation also leads to the synthesis of proinflammatory cytokines and other molecules involved in inflammatory reactions. The investigation of transcription factors mediating these effects has only recently commenced. In general, members of the NF-kappa B family are known to regulate APC function and differentiation, with the RelB subunit being especially important in DC generation. In addition, Ikaros and PU.1 have also been shown to be essential factors for DC differentiation, whereas Oct-2 is upregulated by differentiation towards macrophages. Recently, Fc epsilon RI has been demonstrated to induce NF-kappa B activation via I kappa B-alpha serine phosphorylation and degradation in monocytes and DC. Inhibitors of NF-kappa B activation such as N-acetylcysteine or N-tosyl-L-phenylalanine chloromethyl ketone can suppress Fc epsilon RI-induced TNF-alpha and MCP-1 release. Interestingly, in human epidermal Langerhans' cells (LC), NF-kappa B activation can only be observed when large amounts of Fc epsilon RI are present. In addition, the composition of NF-kappa B complexes differs between monocytes, monocyte-derived DC and LC, suggesting a cell type-specific regulation. Moreover, the transcription factor NFAT is induced upon Fc epsilon RI ligation in human APC. The elucidation of further transcription factors involved in Fc epsilon RI signaling in APC should contribute to the employment of new inhibition strategies for the treatment of atopic and other inflammatory diseases.

Animals↗

IL-4 induces the intracellular expression of the alpha chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells.

BACKGROUND: Recent findings have shown that the surface expression of the high-affinity receptor for IgE (FcepsilonRI) on human CD1a(+) Langerhans cells (LC) and related dendritic cells (DC) in the skin, despite a constant intracellular expression of its alpha chain (FcepsilonRIalpha), is highly up-regulated in atopic dermatitis. Moreover, this surface expression correlates with the IgE serum level, strongly suggesting yet-to-be-defined common signals in the regulation of FcepsilonRI display on LC/DC and IgE synthesis. OBJECTIVES: In this study we examined the influence of different cytokines on the expression of FcepsilonRI on in vitro-generated CD1a(+) LC/DC. METHODS: CD34(+) precursor cells were isolated from cord blood with use of high-gradient magnetic cell sorting, cultured with GM-CSF, TNF-alpha, IL-4, or IFN-gamma, and surface and cytoplasmic staining for flow cytometry were performed. RESULTS: IL-4 strongly enhanced the generation of CD1a(+) LC/DC and also up-regulated the expression of the skin-homing structures E-cadherin and cutaneous lymphocyte antigen. In contrast, IFN-gamma was found to suppress the E-cadherin expression and to be a strong antagonist of IL-4 by inhibiting the production of CD1a(+) cells. Most important, IL-4 induced the cytoplasmic expression of FcepsilonRIalpha in CD1a(+) LC/DC but not its surface expression. This up-regulation was antagonized by IFN-gamma. CONCLUSION: IL-4 is not only a key cytokine in the regulation of IgE but also induces the expression of its receptor binding chain as well as up-regulation of skin homing molecules on LC/DC. Expression of these structures during generation of LC/DC reflects the in vivo situation encountered in LC.

Antigens, CD1↗