Biomedical subjects

D Maurer

Publications and source records attributed to D Maurer.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1999

Rapid improvement in the acuity of infants after visual input.

Visual acuity was assessed in 28 human infants who had been deprived of all patterned visual input by cataracts in one or both eyes until they were treated at 1 week to 9 months of age. Immediately after treatment, acuity was no better than that of normal newborns. Acuity improved significantly over the next month, with some improvement apparent after as little as 1 hour of visual input. Unlike findings at older ages, the pattern of results was the same for eyes treated for monocular and for binocular deprivation. The results indicate that patterned visual input is necessary for the postnatal improvement of human visual acuity and that the onset of such input initiates rapid functional development.

Cataract↗

PubMed1999

Survival, maturation, and function of CD11c- and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines.

Two types of dendritic cells (DC) are circulating in human blood and can be identified by their differential expression of the myeloid Ag CD11c. In this study, we show that CD11c- peripheral blood (PB)-DC correspond to plasmacytoid DC of lymphoid tissue not only by their surface Ag expression profile but, more impressively, by their peculiar ultramorphology. We also demonstrate that CD11c- and CD11c+ DC differ in the quality of their response to and in their requirement for certain cytokines. Freshly isolated CD11c- cells depend on IL-3 for survival and use autocrine or exogenous TNF-alpha as maturation signal, leading to the appearance of a highly dendritic phenotype, the up-regulation and redistribution of MHC class II from lysosomal compartments to the plasma membrane, the increased expression of costimulatory molecules, and the switch from a high Ag-processing to a low Ag-processing/potent accessory cell mode. Surprisingly, IL-4 efficiently killed freshly isolated CD11c- PB-DC, but did not impair the viability of CD11c+ PB-DC and, together with GM-CSF, induced maturation of these cells. A direct functional comparison revealed that neo-Ag-modified and subsequently matured CD11c- but to a lesser extent CD11c+ DC were able to prime naive Ag-specific CD4+ T cells. Our findings show that two diverse DC types respond to certain T cell-derived cytokines in a differential manner and, thus, suggest that suppression or activation of functionally diverse DC types may be a novel mechanism for the regulation of the quantity and quality of immune responses.

Animals↗

PubMed1999

A standardized, a computer-assisted in vitro assay for the assessment of neutrophil transmigration across endothelial monolayers.

We describe an automated, observer-independent and highly reproducible assay for the quantification of transmigrated neutrophils across endothelial monolayers. Endothelial cells grown on collagen gels were loaded with a dye emitting red fluorescence. Neutrophils loaded with dye emitting green fluorescence were allowed to adhere to and transmigrate across endothelial monolayers. For quantification of adherent and migrated cells, randomly selected fields were scanned by confocal laser scan microscopy at defined depths within and below the endothelial monolayers. The images obtained were transferred into the public domain NIH image program and numbers and distribution of cells within scanned sectors were automatically calculated. We demonstrate that adherent neutrophils are easily discriminated from transmigrated cells; absolute numbers of migrated cells can be reproducibly calculated by counting cells at a depth of -20 microm, thus permitting evaluation of large-scale experiments: the efficacy of neutrophil transmigration depends on the level of endothelial activation after TNF stimulation and mAbs to cell surface adhesion molecules interfere with migration in a manner similar to that previously shown in in vivo experiments. This assay lends itself to the identification of molecules influencing in cell migration in each phase of EC activation and to the screening of pro- and anti-migratory properties of biological or pharmacological reagents.

Animals↗

PubMed1999

Oligodeoxynucleotides containing CpG motifs induce IL-12, IL-18 and IFN-gamma production in cells from allergic individuals and inhibit IgE synthesis in vitro.

The effects of phosphorothioate oligonucleotides containing CpG motifs (CpG-ODN) on cultured cells from allergic patients and non-atopic individuals were investigated. In peripheral blood mononuclear cells (PBMC) CpG-ODN led to a significant increase of IFN-gamma. By intracellular cytokine staining, IFN-gamma production could be attributed to NK cells and inhibition experiments indicated an IL-12-dependent mechanism. Moreover, CpG-ODN increased mRNA expression of IL-12 and IL-18 in PBMC. In this respect, no significant difference between allergic and non-atopic individuals was observed. Monocyte-derived dendritic cells were identified as one IL-12- and IL-18-producing source. In addition, stimulation of PBMC derived from atopic patients with CpG-ODN led to a considerable increase of polyclonal IgG and IgM synthesis. In contrast, the production of total IgE was suppressed. CpG-ODN induced a significant rise of IgG and IgM specific for allergens to which the patients were sensitized, whereas allergen-specific IgE levels remained unchanged. Our data suggest that CpG-ODN display a strong influence on the ongoing immune response and might represent potential adjuvants for specific immunotherapy of type I allergy.

Base Sequence↗

PubMed1999

Development of spatial and temporal vision during childhood.

Using the method of limits, we measured the development of spatial and temporal vision beginning at 4 years of age. Participants were adults, and children aged 4, 5, 6, and 7 years (n = 24 per age). Spatial vision was assessed with vertical sine-wave gratings, and temporal vision was assessed with an unpatterned luminance field sinusoidally modulated over time. Under these testing conditions, spatial contrast sensitivity at every frequency increased by at least 0.5 log units between 4 and 7 years of age, at which point it was adult-like. Grating acuity reached adult values at 6 years of age. Temporal vision was more mature: at 4 years of age temporal contrast sensitivity at higher temporal frequencies (20 and 30 Hz) and critical flicker fusion frequency were already adult-like. Sensitivity at lower temporal frequencies (5 and 10 Hz) increased by 0.25 log units after the age of 4 to reach adult levels at age 7. The results suggest that temporal vision matures more rapidly than spatial vision during childhood. Thus, spatial and temporal vision are likely mediated by different underlying neural mechanisms that mature at different rates.

Adolescent↗

PubMed1999

Spatial and temporal vision in patients treated for bilateral congenital cataracts.

Using the method of limits, we measured spatial and temporal vision in 13 children who had been deprived of patterned visual input during infancy until they were treated for dense central cataracts in both eyes. Spatial vision was assessed with vertical sine-wave gratings, and temporal vision was assessed with an unpatterned luminance field sinusoidally modulated over time. Under these testing conditions, spatial contrast sensitivity at low and medium spatial frequencies (0.33-2 c deg-1) was within normal limits, but sensitivity at higher spatial frequencies and grating acuity were reduced on average by 1.3 and 0.5 log units, respectively. Temporal vision was affected less severely, with losses in sensitivity only for low temporal frequencies (5 and 10 Hz), which averaged 0.4 log units. Thus, spatial and temporal vision are likely mediated by different neural mechanisms, that are differentially affected by deprivation.

Adolescent↗

PubMed1999

Effects of eye size on adults' aesthetic ratings of faces and 5-month-olds' looking times.

In two experiments, we investigated the influence of eye size on adults' ratings of faces' attractiveness and 5-month-olds' looking times. Subjects viewed four pairs of female faces that were identical except for the size of the eyes. Whether they saw black-and-white drawings (experiment 1) or coloured photographs (experiment 2), adults rated the faces with larger eyes as more attractive than the faces with smaller eyes. Babies looked equally long at the drawn faces with larger and smaller eyes (experiment 1), but with the more realistic photographed faces, they looked slightly but significantly longer at the versions with larger eyes (experiment 2). Overall, our results suggest that a modest preference for larger eyes that has emerged by 5 months of age may contribute to the development of adult aesthetic preferences.

Adolescent↗

PubMed1999

Effects of the height of the internal features of faces on adults' aesthetic ratings and 5-month-olds' looking times.

We examined the influence of the height of the internal features of faces on adults' ratings of attractiveness and on 5-month-olds' looking times. Subjects viewed drawings or coloured photographs of faces presented in pairs that were identical except that the internal features were at a low height, with a large forehead and small chin; at a high height, with a small forehead and large chin; or at a medium height. Adults rated faces with their features at the medium and low heights as more attractive than faces with their features at the high height, and, at least for drawings, rated faces with medium features as more attractive than faces with low features. Babies looked equally long at faces with their features at various heights except for looking slightly longer at faces with high rather than low features. The results suggest that the influence of feature height on reactions to faces is different for adults and 5-month-olds, and hence that it may be shaped by cultural learning and/or experience with faces sometime after early infancy.

Adolescent↗

PubMed1999

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 F(1) -F(2) pattern of adjacent vowels. However, several studies have reported indications of a correlation between the lower formant frequencies and F(0), 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 F(0) 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 F(0) and relative formant amplitudes. Results are given in exemplary vowel series, and consequences for the psychophysics of the vowel are discussed.

Journal Article↗

PubMed1998

Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation.

In this study, we elucidate the Fc epsilon RI-mediated Ag uptake and presentation mechanisms of dendritic cells (DC). We found that Fc epsilon RI-bound IgE, after polyvalent but not after monovalent ligation, is efficiently internalized into acidic, proteolytic compartments, degraded, and delivered into organelles containing MHC class II, HLA-DM, and lysosomal proteins. To follow the fate of the fragmented ligand, we sought to interfere with invariant chain (Ii) degradation, a process critical for peptide loading of nascent MHC class II molecules. We found DC to express cathepsin (Cat) S, a cysteine protease involved in Ii processing by B cells. Exposure of DC to a specific, active-site inhibitor of Cat S resulted in the loss of anti-Cat S immunoreactivity, led to the appearance of an N-terminal Ii remnant, and decreased the export of newly synthesized MHC class II to the DC surface. Furthermore, inactivation of Cat S as well as blockade of protein neosynthesis by cycloheximide strongly reduced IgE/Fc epsilon RI-mediated Ag presentation by DC. Thus, multimeric ligands of Fc epsilon RI, instead of being delivered into a recycling MHC class H pathway, are channeled efficiently into MIIC (MHC class II compartment)-like organelles of DC, in which Cat S-dependent Ii processing and peptide loading of newly synthesized MHC class II molecules occur. This IgE/Fc epsilon RI-dependent signaling pathway in DC may be a particularly effective route for immunization and a promising target for interfering with the early steps of allergen presentation.

Animals↗

PubMed1998

Anti-FcepsilonRIalpha autoantibodies in autoimmune-mediated disorders. Identification of a structure-function relationship.

Anti-FcepsilonRIalpha autoantibodies (autoAbs) occur and may be of pathogenetic relevance in a subset of chronic urticaria (CU) patients. To analyze the prevalence and magnitude of the humoral anti-FcepsilonRIalpha response in cohorts of CU patients compared with individuals suffering from classic skin- related (auto)immune diseases, we developed an ELISA system for the measurement of anti-FcepsilonRIalpha autoAbs in nonfractionated serum samples. Results obtained using this assay correlated well with those generated by Western blotting. We found IgG anti-FcepsilonRIalpha autoreactivity in 38% of CU patients but not in atopic dermatitis patients, psoriatics, or healthy individuals. We frequently detected anti-FcepsilonRIalpha autoAbs in pemphigus vulgaris (PV, 39%), dermatomyositis (DM, 36%), systemic lupus erythematosus (SLE, 20%), and bullous pemphigoid (BP, 13%). While the autoAb titers in DM, SLE, BP, and PV were similar to those encountered in CU patients, only anti-FcepsilonRIalpha+ CU serum specimens displayed pronounced histamine-releasing activity. The anti-FcepsilonRIalpha autoAbs in CU patients belong predominantly to the complement-fixing subtypes IgG1 and IgG3, whereas in DM, PV, and BP, they were found to be mainly of the IgG2 or IgG4 subtype. Complement-activating properties of anti-FcepsilonRIalpha autoAbs can indeed be of pathogenetic relevance, because C5a receptor blockade on basophils as well as decomplementation reduced drastically the histamine-releasing capacity of most anti-FcepsilonRIalpha-reactive CU sera. As a consequence, therapeutic efforts in CU should aim at altering not only the quantity but also the complement-activating properties of IgG anti-FcepsilonRIalpha autoAbs.

Antigens, CD↗