Showing papers by "University of Würzburg published in 1999"

Wing rotation and the aerodynamic basis of insect flight.

Abstract: The enhanced aerodynamic performance of insects results from an interaction of three distinct yet interactive mechanisms: delayed stall, rotational circulation, and wake capture. Delayed stall functions during the translational portions of the stroke, when the wings sweep through the air with a large angle of attack. In contrast, rotational circulation and wake capture generate aerodynamic forces during stroke reversals, when the wings rapidly rotate and change direction. In addition to contributing to the lift required to keep an insect aloft, these two rotational mechanisms provide a potent means by which the animal can modulate the direction and magnitude of flight forces during steering maneuvers. A comprehensive theory incorporating both translational and rotational mechanisms may explain the diverse patterns of wing motion displayed by different species of insects.

Injection and detection of a spin-polarized current in a light-emitting diode

Abstract: The field of magnetoelectronics has been growing in practical importance in recent years1 For example, devices that harness electronic spin—such as giant-magnetoresistive sensors and magnetoresistive memory cells—are now appearing on the market2 In contrast, magnetoelectronic devices based on spin-polarized transport in semiconductors are at a much earlier stage of development, largely because of the lack of an efficient means of injecting spin-polarized charge Much work has focused on the use of ferromagnetic metallic contacts3,4, but it has proved exceedingly difficult to demonstrate polarized spin injection More recently, two groups5,6 have reported successful spin injection from an NiFe contact, but the observed effects of the spin-polarized transport were quite small (resistance changes of less than 1%) Here we describe a different approach, in which the magnetic semiconductor BexMnyZn1-x-ySe is used as a spin aligner We achieve injection efficiencies of 90% spin-polarized current into a non-magnetic semiconductor device The device used in this case is a GaAs/AlGaAs light-emitting diode, and spin polarization is confirmed by the circular polarization state of the emitted light

A Simplified Risk Score for Predicting Postoperative Nausea and Vomiting Conclusions from Cross-validations between Two Centers

Abstract: BackgroundRecently, two centers have independently developed a risk score for predicting postoperative nausea and vomiting (PONV). This study investigated (1) whether risk scores are valid across centers and (2) whether risk scores based on logistic regression coefficients can be simplified without

Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

Abstract: Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice.

Abstract: Stimulation of cardiac β1-adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac β-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of β1-adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by ≈50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of ≈20%. We conclude that overexpression of β1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased β1-adrenergic receptor signalling is ultimately detrimental.

Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors.

Abstract: Cannabinoids, including the endogenous ligand arachidonyl ethanolamide (anandamide), elicit not only neurobehavioral but also cardiovascular effects. Two cannabinoid receptors, CB1 and CB2, have been cloned, and studies with the selective CB1 receptor antagonist SR141716A have implicated peripherally located CB1 receptors in the hypotensive action of cannabinoids. In rat mesenteric arteries, anandamide-induced vasodilation is inhibited by SR141716A, but other potent CB1 receptor agonists, such as HU-210, do not cause vasodilation, which implicates an as-yet-unidentified receptor in this effect. Here we show that “abnormal cannabidiol” (Abn-cbd) is a neurobehaviorally inactive cannabinoid that does not bind to CB1 receptors, yet causes SR141716A-sensitive hypotension and mesenteric vasodilation in wild-type mice and in mice lacking CB1 receptors or both CB1 and CB2 receptors. Hypotension by Abn-cbd is also inhibited by cannabidiol (20 μg/g), which does not influence anandamide- or HU-210-induced hypotension. In the rat mesenteric arterial bed, Abn-cbd-induced vasodilation is unaffected by blockade of endothelial NO synthase, cyclooxygenase, or capsaicin receptors, but it is abolished by endothelial denudation. Mesenteric vasodilation by Abn-cbd, but not by acetylcholine, sodium nitroprusside, or capsaicine, is blocked by SR141716A (1 μM) or by cannabidiol (10 μM). Abn-cbd-induced vasodilation is also blocked in the presence of charybdotoxin (100 nM) plus apamin (100 nM), a combination of K+-channel toxins reported to block the release of an endothelium-derived hyperpolarizing factor (EDHF). These findings suggest that Abn-cbd and cannabidiol are a selective agonist and antagonist, respectively, of an as-yet-unidentified endothelial receptor for anandamide, activation of which elicits NO-independent mesenteric vasodilation, possibly by means of the release of EDHF.

Excess of High Activity Monoamine Oxidase A Gene Promoter Alleles in Female Patients with Panic Disorder

Abstract: A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.

A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.

Abstract: Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission.

Abstract: The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney1. α2-Adrenergic receptors are known to have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system2,3,4,5; however, the individual roles of the three highly homologous α2-adrenergic-receptor subtypes (α2A, α2B, α2C) in this process are not known. We have now studied neurotransmitter release in mice in which the genes encoding the three α2-adrenergic-receptor subtypes were disrupted. Here we show that both the α2A- and α2C-subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. α2A-Adrenergic receptors inhibit transmitter release at high stimulation frequencies, whereas the α2C-subtype modulates neurotransmission at lower levels of nerve activity. Both low- and high-frequency regulation seem to be physiologically important, as mice lacking both α2A- and α2C-receptor subtypes have elevated plasma noradrenaline concentrations and develop cardiac hypertrophy with decreased left ventricular contractility by four months of age.

Mutations in the skeletal muscle α-actin gene in patients with actin myopathy and nemaline myopathy

Abstract: Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.

The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile

Abstract: Background: Some patients with pemphigus vulgaris (PV) have mucous membrane erosions with minimal skin involvement (mucosal dominant type), and others show extensive skin blisters and erosions in addition to mucous membrane involvement (mucocutaneous type). Patients with pemphigus foliaceus (PF) show only skin involvement. Objective: The purpose of this study is to determine whether there is a difference in autoantibody profile among mucosal dominant PV, mucocutaneous PV, and PF. Methods: Antibody titer against desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) were measured with enzyme-linked immunosorbent assay using recombinant Dsg1 and Dsg3. Sera were obtained during clinically active disease from 24 patients with mucosal dominant PV, 20 with mucocutaneous PV, and 23 with PF. Results: All sera samples from patients with mucosal dominant PV sera were negative against Dsg1 but positive against Dsg3. All sera samples from those with mucocutaneous PV were positive against both Dsg1 and Dsg3. All sera samples from patients with PF were positive against Dsg1, but negative against Dsg3. Conclusion: Each subtype has its own anti-Dsg autoantibody profile, indicating that the clinical phenotype of pemphigus is defined by the autoantibody profile. (J Am Acad Dermatol 1999;40:167-70.)

Apoplastic barriers in roots: chemical composition of endodermal and hypodermal cell walls

Abstract: ment by forming extensive surface areas. There are clear similarities and diVerences in functional properties and Based on the characterization of the chemical com- structural demands of these above-ground and belowposition of endodermal and hypodermal cell walls ground interfaces across which interactions occur. Both isolated from seven monocotyledonous and three dico- interfaces have in common that they must protect the tyledonous plant species, a model of the composition living tissue from infection by pathogens ( Kerstiens, 1996; of apoplastic barriers in roots is proposed. Depending Agrios, 1997). The leaf epidermis carries stomata allowing on the species, endodermal and hypodermal cell walls the regulation of gas exchange and transpiration (Larcher, of roots contained varying amounts of the biopolymers 1994). In addition, more than 90% of the leaf epidermis suberin, lignin, cell wall proteins, and carbohydrates. is covered by a lipophilic cuticle which prevents unconAlthough analysis of the chemical composition of these trolled water loss and leaching of nutrients from the

Fine Structure of Biexciton Emission in Symmetric and Asymmetric CdSe/ZnSe Single Quantum Dots

Abstract: The influence of quantum dot (QD) asymmetry on the emission of single three-dimensionally confined biexcitons in II-VI semiconductor nanostructures has been studied by magnetophotoluminescence spectroscopy. Investigating both the biexciton and the single-exciton transition in the same single QD, we obtain a unified picture of the impact of electron-hole exchange interaction on the fine structure and the polarization properties of optical transitions in QDs. The exchange splitting is demonstrated to have a strong influence on the derivation of the biexciton binding energy, which we determine to be about 17 meV, much less than the separation between exciton and biexciton lines ( $\ensuremath{\approx}24$ meV) in the spectra.

Developmental Requirement of gp130 Signaling in Neuronal Survival and Astrocyte Differentiation

Abstract: gp130 is a signal-transducing receptor component used in common by the interleukin-6 (IL-6) family of hematopoietic and neurotrophic cytokines, including IL-6, IL-11, leukemia-inhibitory factor, ciliary neurotrophic factor, oncostatin-M, and cardiotrophin-1. We have examined in this study a role of gp130 in the nervous system by analyzing developmental cell death of several neuronal populations and the differentiation of astrocytes in gp130-deficient mice. A significant reduction was observed in the number of sensory neurons in L5 dorsal root ganglia and motoneurons in the facial nucleus, the nucleus ambiguus, and the lumbar spinal cord in gp130 −/− mice on embryonic day 18.5. On the other hand, no significant neuronal loss was detectable on day 14.5, suggesting a physiological role of gp130 in supporting newly generated neurons during the late phase of development when naturally occurring cell death takes place. Moreover, expression of an astrocyte marker, GFAP, was severely reduced in the brain of gp130 −/− mice. Our data demonstrate that gp130 expression is essential for survival of subgroups of differentiated motor and sensory neurons and for the differentiation of major populations of astrocytes in vivo .

Vulnerability of the nigrostriatal system as detected by transcranial ultrasound

Abstract: Objective: To assess the incidence of a hyperechogenic substantia nigra (SN) by transcranial sonography (TCS) in healthy people and to evaluate whether an enlarged hyperechogenic SN area is associated with functional impairment of the nigrostriatal system. Background and Methods: Until now, preclinical impairment of the nigrostriatal system could be identified only by functional neuroimaging techniques such as PET in selected groups of patients. TCS is a new, noninvasive ultrasound technique that has demonstrated an increased echogenicity of the SN in patients with PD, whereas in most healthy individuals, the SN is either barely detectable or undetectable by TCS. Results: Of 330 healthy volunteers, 8.6% exhibited an increased echogenicity of the SN. From these, 10 clinically healthy individuals with distinct unilateral or bilateral hyperechogenic signals in the SN region (SN area above 0.25 cm 2 ) underwent comprehensive motor testing, neuropsychological assessment, MRI, and [ 18 F]-dopa PET examination. With regard to motor functions, these individuals did not differ from 10 age- and sex-matched controls with a low echogenic SN and an area of echogenic signals below 0.2 cm 2 . Enlargement of hyperechogenic areas in the 10 healthy individuals was associated with a marked decrease in the accumulation of [ 18 F]-dopa in the caudate nucleus and putamen. Conclusions: Substantia nigra hyperechogenicity appears to indicate a functional impairment of the nigrostriatal system. Transcranial sonography may be a suitable method of identifying persons at risk of nigrostriatal alterations, making possible the introduction of early neuroprotective therapy.

The History of Low-Mass Star Formation in the Upper Scorpius OB Association

Abstract: We use a large sample of about 100 low-mass pre–main-sequence (PMS) stars in the Upper Scorpius OB association to explore the star formation history and the initial mass function of this association. Upper Scorpius is an ideal target for such a study, because the star formation process there is finished. The PMS stars have recently been found in a spatially unbiased wide-field survey of X-ray–selected stars in a 160 deg2 area, covering the Upper Scorpius association nearly completely. Following the optical characterization of these PMS stars, we present a new HR diagram for this association. We perform a detailed analysis of the HR diagram, taking proper account of the uncertainties and the effects of unresolved binaries, and derive ages and masses for the PMS stars. We find that the low-mass PMS stars have a mean age of about 5 Myr and show no evidence for a large age dispersion. This agrees very well with the age of 5–6 Myr previously found for the massive stars and shows that low-mass and high-mass stars are coeval and cospatial and thus have formed together. We conclude that the star formation process in Upper Scorpius was probably triggered by the shock wave of a supernova explosion in the nearby Upper Centaurus-Lupus association. After a short burst of very high star formation activity, which lasted only for a few Myr, star formation in Upper Scorpius was halted, probably by the strong winds and the ionizing radiation of the numerous massive stars that dispersed the molecular cloud.

Electron and Hole g Factors and Exchange Interaction from Studies of the Exciton Fine Structure in In 0.60 Ga 0.40 As Quantum Dots

Abstract: Self-assembled ${\mathrm{In}}_{0.60}{\mathrm{Ga}}_{0.40}\mathrm{As}$ quantum dots (QD's) have been studied by single dot magnetophotoluminescence spectroscopy ( $B\ensuremath{\le}8\mathrm{T}$). At $B\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0$ a splitting of the exciton ( $X$) emission is observed which we ascribe to an asymmetry of the confinement potential. With increasing $B$ the emission splits into a quadruplet corresponding to the $m\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\ifmmode\pm\else\textpm\fi{}2$ and $\ifmmode\pm\else\textpm\fi{}1X$ states, which originates from a reduction of the cubic symmetry of the QD's. From the spectroscopic data we obtain values for the electron ( $e$) and hole ( $h$) $g$ factors. We also determine the $X$ singlet-triplet splitting which is found to be enhanced over bulk values by about an order of magnitude due to the increase of the $e\ensuremath{-}h$ overlap in the QD's.

Increased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype.

Abstract: Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α-synuclein (α-SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α-SYN and apolipoprotein E, which is a major risk factor for late-onset Alzheimer's disease, prompted us to investigate the influence of different α-SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α-SYN gene (NACP-Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoe4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early-onset PD patients (age at onset, <50 years) than in late-onset PD. Regarding the combination of the Apoe4 allele and allele 1 of the α-SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8-fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617

Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations.

Abstract: The hSNF5/INI1 gene which encodes a member of the SWI/SNF chromatin ATP-dependent remodeling complex, is a new tumor suppressor gene localized on chromosome 22q11.2 and recently shown to be mutated in malignant rhabdoid tumors. We have searched for hSNF5/INI1 mutations in 229 tumors of various origins using a screening method based on denaturing high-performance liquid chromatography. A total of 31 homozygous deletions and 36 point alterations were identified. Point mutations were scattered along the coding sequence and included 15 nonsense, 15 frameshift, three splice site, two missense and one editing mutations. Mutations were retrieved in most rhabdoid tumors, whatever their sites of occurrence, indicating the common pathogenetic origin of these tumors. Recurrent hSNF5/INI1 alterations were also observed in choroid plexus carcinomas and in a subset of central primitive neuroectodermal tumors (cPNETs) and medulloblastomas. In contrast, hSNF5/INI1 point mutations were not detected in breast cancers, Wilms' tumors, gliomas, ependymomas, sarcomas and other tumor types, even though most analyzed cases harbored loss of heterozygosity at 22q11.2 loci. These results suggest that rhabdoid tumors, choroid plexus carcinomas and a subset of medulloblastomas and cPNETs share common pathways of oncogenesis related to hSNF5/INI1 alteration and that hSNF5/INI1 mutations define a genetically homogeneous family of highly aggressive cancers mainly occurring in young children and frequently, but not always, exhibiting a rhabdoid phenotype.