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Biomedical subjects

D Maurer

Publications and source records attributed to D Maurer.

At least 19 recordsLinked to original sources
PubMed2003

Longer VEP latencies and slower reaction times to the onset of second-order motion than to the onset of first-order motion.

We compared visual evoked potentials and psychophysical reaction times to the onset of first- and second-order motion. The stimuli consisted of luminance-modulated (first-order) and contrast-modulated (second-order) 1 cpd vertical sine-wave gratings drifting rightward for 140 ms at a velocity of 6 degrees /s. For each condition, we analysed the latencies and peak-to-baseline amplitudes of the P1 and N2 peaks recorded at Oz. For first-order motion, both P1 and N2 peaks were present at low (3%) contrast (i.e., depth modulations) whereas for second-order motion they appeared only at higher (25%) contrasts. When the two types of motion were equated for visibility, responses were slower for second-order motion than for first-order motion: about 44 ms slower for P1 latencies, 53 ms slower for N2 latencies, and 76 ms slower for reaction times. The longer VEP latencies for second-order motion support models that postulate additional processing steps for the extraction of second-order motion. The slower reaction time to the onset of second-order motion suggests that the longer neurophysiological analysis translates into slower detection.

Adult↗
PubMed2003

Donor dependent, interferon-gamma induced HLA-DR expression on human neutrophils in vivo.

Neutrophils are effector cells of innate immune responses. Stimulated by interferon-gamma (IFN-gamma) to express HLA-DR, neutrophils acquire accessory cell functions for superantigen-mediated T cell activation. In vitro HLA-DR induction on neutrophils varies in a functionally relevant way as levels of MHC class II expression and magnitude of neutrophil induced T cell responses are correlated functions. The aim of this study was to assess whether IFN-gamma induces HLA-DR on human neutrophils in a donor dependent fashion in vivo and to define regulatory events operative in MHC class II expression of neutrophils. In vivo administration of rhIFN-gamma in 55 patients with renal cell carcinoma resulted in a varying increase of HLA-DR on neutrophils. By setting a cut-off for response at>10% HLA-DR positive neutrophils, HLA-DR responders (51%) were as frequent as nonresponders (49%). In vivo kinetic studies revealed a peak expression of HLA-DR on neutrophils 48 h after rhIFN-gamma application, while nonresponders remained HLA-DR negative over a 72-h period. In vitro IFN-gamma stimulated neutrophils recapitulated the response profiles observed in vivo. No differences in IFN-gamma dependent CD64 and invariant chain expression, and IFN-gamma serum levels were observed among the response subgroups. HLA-DR mRNA was detected in neutrophils from rhIFN-gamma treated responders and nonresponders, HLA-DR protein solely in lysates of responder neutrophils. IFN-gamma stimulated HLA-DR expression on neutrophils is subject to donor dependent variations in vivo, which result from rather post-transcriptional than transcriptional regulation. Due to their abundance in inflammatory reactions heterogeneous HLA-DR expression by neutrophils could determine the outcome of superantigen-driven diseases.

Adult↗
PubMed2001

Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages.

A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin(+) LECs and podoplanin(-) BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3alpha/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.

Adult↗
PubMed2001

Monomorphic molecules function as additional recognition structures on haptenated target cells for HLA-A1-restricted, hapten-specific CTL.

Hapten-specific T cells have been shown to recognize haptenated peptides with high avidity and, in some instances, with promiscuous MHC restriction. In this study, the impact of Ag density on MHC restriction of a CTL response specific to the trinitrophenyl (TNP) hapten was investigated. In this study, we demonstrate a novel recognition mechanism used by TNP-specific CD8(+) CTL in the presence of high Ag doses. Although low levels of TNP epitopes on target cells allowed for HLA-A1-restricted CTL activity only, entirely MHC-independent target cell recognition became operative at high TNP loading. In both cases, recognition was mediated by the TCR. This MHC-independent recognition is target cell type restricted and critically involves in our model direct recognition of the ectonucleotidase family surface molecule CD39 by the CTL.

Adenosine Triphosphatases↗
PubMed2001

Cytokines regulate proteolysis in major histocompatibility complex class II-dependent antigen presentation by dendritic cells.

Endo/lysosomal proteases control two key events in antigen (Ag) presentation: the degradation of protein Ag and the generation of peptide-receptive major histocompatibility complex (MHC) class II molecules. Here we show that the proinflammatory cytokines tumor necrosis factor alpha and interleukin (IL)-1beta rapidly increase the activity of cathepsin (cat) S and catB in human dendritic cells (DCs). As a consequence, a wave of MHC class II sodium dodecyl sulfate stable dimer formation ensues in a catS-dependent fashion. In contrast, the antiinflammatory cytokine IL-10 renders DCs incapable of upregulating catS and catB activity and in fact, attenuates the level of both enzymes. Suppressed catS and catB activity delays MHC class II sodium dodecyl sulfate stable dimer formation and impairs Ag degradation. In DCs exposed to tetanus toxoid, IL-10 accordingly reduces the number of MHC class II-peptide complexes accessible to tetanus toxoid-specific T cell receptors, as analyzed by measuring T cell receptor downregulation in Ag-specific T cell clones. Thus, the control of protease activity by pro- and antiinflammatory cytokines is an essential feature of the Ag presentation properties of DCs.

B-Lymphocytes↗
PubMed2001

The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors.

The lymphatic vessels (lymphatics) play an important role in channeling fluid and leukocytes from the tissues to the secondary lymphoid organs. In addition to driving leukocyte egress from blood, chemokines have been suggested to contribute to leukocyte recirculation via the lymphatics. Previously, we have demonstrated that binding sites for several pro-inflammatory beta-chemokines are found on the endothelial cells (ECs) of lymphatics in human dermis. Here, using the MIP-1alpha isoform MIP-1alphaP, we have extended these studies to further support the contention that the in situ chemokine binding to afferent lymphatics exhibits specificity akin to that observed in vitro with the promiscuous beta-chemokine receptor D6. We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6 probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive lymphatics were also abundant in mucosa and submucosa of small and large intestine and appendix, but not observed in several other organs tested. In lymph nodes, D6 immunoreactivity was present on the afferent lymphatics and also in subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6-positive. Peripheral blood cells and the ECs of blood vessels and high endothelial venules were consistently nonreactive with anti-D6 antibodies. Additionally, we have demonstrated that D6 immunoreactivity is detectable in some malignant vascular tumors suggesting they may be derived from, or phenotypically similar to, lymphatic ECs. This is the first demonstration of chemokine receptor expression by lymphatic ECs, and suggests that D6 may influence the chemokine-driven recirculation of leukocytes through the lymphatics and modify the putative chemokine effects on the development and growth of vascular tumors.

Adult↗
PubMed2001

Definition, classification, and routine diagnosis of urticaria: a consensus report.

Urticaria is a well-known disease entity; however, with an increasing understanding of the molecular mechanisms involved in its pathogenesis, there is also growing evidence for a heterogeneity of urticaria. Currently it is sometimes difficult to compare divergent data reported by different centers researching urticaria due to a lack of precisely described patient populations. A consensus definition and classification of the disease and its subtypes, taking into account new developments, are therefore needed. In addition, this consensus report provides a guideline for diagnostic procedures in different subtypes of urticaria.

Algorithms↗
PubMed2001

The influence of binocular visual deprivation on the development of visual-spatial attention.

This article examines the effects of visual input on the development of attention by comparing normal children to children, all more than 8 years old, who had been treated for bilateral congenital cataracts during infancy. In Experiment 1, patients pushed a button as soon as they detected a target that appeared 100, 400, or 800 msec after a central cue. The cue either validly cued the upcoming location or invalidly cued the wrong location. Patients (n = 16) performed normally at the 100 msec and 400 msec stimulus onset asynchrony (SOA). However, when the cue preceded the target by the 800 msec SOA, patients' reaction times were not affected by the validity of the cue, especially when deprivation had extended past 4 months of age. In Experiment 2, patients indicated which of two shapes appeared in the periphery 400 msec after a central cue, with those shapes surrounded by compatible or incompatible distractors. Patients (n = 15) differed from age-matched controls in (a) being slowed more by incompatible distractors on invalid trials, and (b) tending to show a larger than normal effect of the validity of the cue preceding targets in the upper visual field. Together, these findings suggest that the normal development of attention is influenced by early visual experience.

Adolescent↗
PubMed2000

Dermal microvascular endothelial cells express the 180-kDa macrophage mannose receptor in situ and in vitro.

Expression of the 180-kDa mannose receptor (MR) is mainly found on cells of the macrophage lineage. MR mediates the uptake of micro-organisms and host-derived glycoproteins. We demonstrate that endothelium of the human skin in situ and dermal microvascular endothelial cells (DMEC) in vitro expressed MR at both the protein and mRNA levels. In contrast, HUVEC were consistently negative for MR expression. DMEC internalized dextran as well as Escherichia coli by the way of MR into acidic phagosomes, only a few of which fused with CD63- and lysosomal-associated membrane glycoprotein-2-positive lysosomes. This contrasts with the situation in monocyte-derived dendritic cells, where almost all of the MR-Ag complexes reached CD63- and lysosomal-associated membrane glycoprotein-2-positive compartments, indicating differences in the phagolysosomal fusion rate between DMEC and dendritic cells. In conclusion, DMEC express functional MR, a finding that corroborates a role of skin endothelium in Ag capture/clearing.

Cell Membrane↗
PubMed2000

The oculomotor distractor effect in normal and hemianopic vision.

The present study investigated the inhibitory effect of visual distractors on the latency of saccades made by hemianopic and normal human subjects. The latency of saccades made by hemianopic subjects to stimuli in their intact visual field was not affected by visual distractors presented within their hemianopic field. In contrast, the latency of saccades made by normal subjects was increased significantly under distractor conditions. The latency increase was larger for temporal than nasal distractors. The results are inconsistent with previous proposals that the crossed retinotectal pathway from the nasal hemiretina to the superior colliculus may mediate a blindsight inhibitory effect when distractors appear within a hemianopic temporal visual field. Instead, the distractor effect appears to reflect the normal processes involved in saccade target selection which may be mediated by a circuit involving both cortical and subcortical structures.

Adolescent↗
PubMed2000

Influence of monocular deprivation during infancy on the later development of spatial and temporal vision.

Using the method of limits, we measured spatial and temporal vision in 15 patients, aged 4-28 years, who had been monocularly deprived of patterned visual input during infancy by a dense cataract. All patients showed losses in both spatial and temporal vision, with greater losses in spatial than in temporal vision. Losses were smaller when there had been more patching of the non-deprived eye. The results indicate that visual deprivation has smaller effects on the neural mechanisms mediating temporal vision than on those mediating spatial vision.

Adolescent↗
PubMed2000

The development of symmetrical OKN in infants: quantification based on OKN acuity for nasalward versus temporalward motion.

We quantified OKN asymmetry in 140 normal infants, 3-24 months old, by varying spatial frequency to determine OKN acuity for temporal-to-nasal (T-N) versus nasal-to-temporal (N-T) motion. At all ages, OKN acuity was asymmetrical (better for T-N than for N-T motion) but the size of the asymmetry decreased from 3.2 to 0.7 octaves between 3-24 months, primarily because of improvements in OKN acuity for N-T motion. The results suggest that immaturities in the cortical pathways involved in OKN persist until at least 2 years of age.

Child Development↗
PubMed2000

Anti-FcepsilonRIalpha serum autoantibodies in different subtypes of urticaria.

BACKGROUND: In recent years, a histamine-releasing anti-FcepsilonRIalpha autoantibody has been demonstrated in about one-third of patients with chronic urticaria. However, its clinical significance is still unclear. The objective was to detect a possible correlation between the occurrence of the anti-FcepsilonRIalpha autoantibody and the clinical type or cause of urticaria. METHODS: Sera from 66 consecutively seen in- and outpatients with various types of urticaria and five healthy controls were examined for the presence of anti-FcepsilonRIalpha autoantibodies with a sandwich ELISA technique. In addition, basophil histamine release was studied in 13 autoantibody-positive sera. RESULTS: Anti-FcepsilonRIalpha autoantibodies were found in 17/48 patients with chronic urticaria, in 2/4 with angioedema, in 1/2 with urticarial vasculitis, and in 2/11 with dermographic urticaria. However, no anti-FcepsilonRIalpha autoantibodies were detected in acute, cold, or delayed-pressure urticaria; in urticaria pigmentosa; or in normal controls. Of all chronic urticaria patients, 22 were classified as idiopathic since no underlying cause could be found. Of this group, seven were seropositive for anti-FcepsilonRIalpha. However, anti-FcepsilonRIalpha was also found in patients who went into remission after treatment of identified causes; namely, in one with type I allergy, one with drug intolerance, one with Helicobacter infection, and six with food intolerance. The autoantibody was also detected in 2/4 patients with associated autoimmune diseases. Functional activity was shown in basophil histamine release in 3/4 autoantibody-positive sera of patients with chronic idiopathic urticaria and in 4/6 autoantibody-positive sera of patients who went into remission after the treatment of underlying causes. CONCLUSIONS: These data confirm that anti-FcepsilonRIalpha autoantibodies in urticaria are mostly found in chronic urticaria. Furthermore, their detection independently of the apparent cause of the urticaria suggests that as yet unidentified mechanisms must be operative, possibly related to the chronic inflammatory process and/or individual predispositions that favor their induction.

Autoantibodies↗
PubMed2000

What is the most promising strategy for the treatment of metastasizing melanoma?

The treatment of patients with metastasizing melanoma, still one of the most deadly diseases in modern medicine, ranks among the greatest challenges that a clinician has to face. Metastatic melanoma also is one of the most profound sources of clinical frustration, since it provides far more ultimately defeating experiences than clinical victories. At the same time, the fascinating biology of melanoma has invited the study of this neuroectodermal tumor as a model system for dissecting many of the key problems of modern oncology, ranging from molecular oncogenesis via the controls of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis to tumor immunosurveillance and tumor drug resistance. Together with the dire need to develop more effective treatment modalities for improving both life expectancy and quality of life of affected patients, this has made metastatic melanoma a favorite model for the exploration of innovative strategies for tumor management. Encouragingly, many of these have already generated very promising results in animal models. However, this impressive level of research progress in conquering melanoma in the animal room contrasts rather pitifully with the actual progress made on the ward. This CONTROVERSIES feature, therefore, critically and soberly reviews the state of the art of treating metastatic melanoma today (distinguishing between nodal and distant metastases), and sharply defines unresolved or comparatively neglected key problems. In addition, this feature highlights several novel, provocative, hitherto underappreciated, yet potentially promising treatment approaches that deserve systematic exploration. Hopefully, this will offer further inspiration for the design and pursuit of innovative anti-melanoma strategies off-the-beaten-track.

Humans↗
PubMed2000

Formant pattern ambiguity of vowel sounds.

The formant frequencies of a particular vowel vary according to the speaker group and to coarticulation. Therefore, overlapping formant patterns of different vowels are commonly related to sex and age differences and to coarticulation, and are considered to concern mainly the F1-F2 pattern of adjacent vowels. However, several studies have reported indications of a correlation between the lower formant frequencies and F0, as well as of the appearance of different formant numbers relevant to vowel identity. As a consequence, the overlap between formant patterns of different vowels might be more substantial than has traditionally been assumed. Within the present study, therefore, the extent to which a given formant pattern can represent different vowels was investigated for natural Swiss German vowels produced monotonously and in isolation by men, women and children at F0 of 85-870 Hz. Similar formant patterns were found for vocalizations of different vowels with both small and large phonetic distances, and within the entire frequency ranges of the formants relevant for phoneme identity. For vowel sounds displaying ambiguous formant patterns, the main spectral characteristics related to differences in their perceptual identity were found to concern F0 and relative formant amplitudes. Results are given in exemplary vowel series, and consequences for the psychophysics of the vowel are discussed.

Adolescent↗
PubMed1999

Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells.

Certain types of dendritic cells (DCs) appear in inflammatory lesions of various etiologies, whereas other DCs, e.g., Langerhans cells (LCs), populate peripheral organs constitutively. Until now, the molecular mechanism behind such differential behavior has not been elucidated. Here, we show that CD1a(+) LC precursors respond selectively and specifically to the CC chemokine macrophage inflammatory protein (MIP)-3alpha. In contrast, CD14(+) precursors of DC and monocytes are not attracted by MIP-3alpha. LCs lose the migratory responsiveness to MIP-3alpha during their maturation, and non-LC DCs do not acquire MIP-3alpha sensitivity. The notion that MIP-3alpha may be responsible for selective LC recruitment into the epidermis is further supported by the following observations: (a) MIP-3alpha is expressed by keratinocytes and venular endothelial cells in clinically normal appearing human skin; (b) LCs express CC chemokine receptor (CCR)6, the sole MIP-3alpha receptor both in situ and in vitro; and (c) non-LC DCs that are not found in normal epidermis lack CCR6. The mature forms of LCs and non-LC DCs display comparable sensitivity for MIP-3beta, a CCR7 ligand, suggesting that DC subtype-specific chemokine responses are restricted to the committed precursor stage. Although LC precursors express primarily CCR6, non-LC DC precursors display a broad chemokine receptor repertoire. These findings reflect a scenario where the differential expression of chemokine receptors by two different subpopulations of DCs determines their functional behavior. One type, the LC, responds to MIP-3alpha and enters skin to screen the epidermis constitutively, whereas the other type, the "inflammatory" DC, migrates in response to a wide array of different chemokines and is involved in the amplification and modulation of the inflammatory tissue response.

Antigens, CD1↗
PubMed1999

CD34+ cell-derived CD14+ precursor cells develop into Langerhans cells in a TGF-beta 1-dependent manner.

Langerhans cells (LC) are CD1a+E-cadherin (E-cad)+Birbeck granule+ but CD11b-CD36-factor XIIIa (FXIIIa)- members of the dendritic cell (DC) family. Evidence holds that LC originate from CD1a+CD14- rather than CD14+CD1a- progenitors, both of which arise from GM-CSF/TNF-alpha-stimulated CD34+ stem cells. The CD14+CD1a- progenitors, on the other hand, can give rise to a separate DC type characterized by its CD1a+CD11b+CD36+FXIIIa+E-cad-BG- phenotype (non-LC DC). Although GM-CSF/TNF-alpha are important for both LC and non-LC DC differentiation, TGF-beta 1 is thought to preferentially promote LC development in vitro and in vivo. However, the hemopoietic biology of this process and the nature of TGF-beta 1-responsive LC precursors (LCp) are not well understood. Here we show that CD14+ precursors in the presence, but not in the absence, of TGF-beta 1 give rise to a progeny that fulfills all major criteria of LC. In contrast, LC development from CD1a+ progenitors was TGF-beta 1 independent. Further studies revealed that CD14+ precursors contain a CD11b+ and a CD11b- subpopulation. When either subset was stimulated with GM-CSF/TNF-alpha and TGF-beta 1, only CD14+CD11b- cells differentiated into LC. The CD11b+ cells, on the other hand, acquired non-LC DC features only. The higher doubling rates of cells entering the CD14+ LCp rather than the CD1a+ LCp pathway add to the importance of TGF-beta 1 for LC development. Because CD14+CD11b- precursors are multipotent cells that can enter LC or macrophage differentiation, it is suggested that these cells, if present at the tissue level, endow a given organ with the property to generate diverse cell types in response to the local cytokine milieu.

Adult↗