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S Kraft

Publications and source records attributed to S Kraft.

At least 37 records · Page 2Linked to original sources
PubMed2000

Atopic dermatitis: pathogenetic mechanisms.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing incidence and socio-economical relevance. The diagnosis is made on clinical grounds and different diagnostic criteria sets have been established. The majority of all AD cases is associated with a sensitization to environmental allergens and increased serum IgE (so-called extrinsic AD), but about 10--30% of all cases suffer from the so-called intrinsic AD, which obviously lacks any link to the classical atopic diathesis. The genetic background of AD has been investigated by target gene approach by different groups with mostly contradictory results for each of the genes under study. An imbalance in the spectrum of Th1/Th2 responses, a disturbed prostaglandin metabolism, intrinsic defects in keratinocyte function, delayed eosinophil apoptosis, IgE-mediated facilitated antigen presentation by epidermal dendritic cells, a two phase model of the inflammatory response and staphylococcal superantigen effects are among the currently studied pathogenetical aspects of extrinsic AD, which are reviewed in this paper.

Dermatitis, Atopic↗
PubMed2000

The high-affinity IgE receptor (FcepsilonRI) blocks apoptosis in normal human monocytes.

Monocytes have a limited life span, and their homeostasis is regulated by apoptosis in vivo. When cultured in the absence of appropriate exogenous stimuli, they undergo apoptosis, but under the influence of survival signals, these cells differentiate into macrophages or dendritic cells. Here we show that ligation of the high-affinity IgE receptor (FcepsilonRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcepsilonRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcepsilonRI ligation enhances the expression of the antiapoptotic molecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimulated cells with culture supernatants of FcepsilonRI-activated monocytes prolongs their life span, whereas CD95/Fas expression remains unaffected. The incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-alpha, whereas elimination of IL-1beta, GM-CSF, or IL-12 has no effect. These results indicate that FcepsilonRI mediates signals preventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-alpha in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis.

Antibodies, Monoclonal↗
PubMed1999

Definition of an unexpected ligand recognition motif for alphav beta6 integrin.

Integrin interactions with extracellular matrix proteins are mediated by brief oligopeptide recognition sequences, and synthetic peptides containing such sequences can inhibit integrin binding to the matrix. The RGD peptide motif is recognized by many integrins including alphav beta6, a specific receptor for fibronectin thought to support epithelial cell proliferation during wound healing and carcinoma progression. We report here the discovery of an unexpected non-RGD recognition motif for integrin alphav beta6. We compared the recognition profiles of recombinant alphav beta6 and alphav beta3 integrins by using phage display screening employing 7-mer and 12-mer peptide libraries. As predicted, phages binding strongly to alphav beta3 contained ubiquitous RGD sequences. However, on alphav beta6, in addition to RGD- containing phages, one-quarter of the population from the 12-mer library contained the distinctive consensus motif DLXXL. A synthetic DLXXL peptide, RTDLDSLRTYTL, selected from the phage sequences (clone-1) was a selective inhibitor of RGD-dependent ligand binding to alphav beta6 in isolated receptor assays (IC50 = 20 nM), and in cell adhesion assays (IC50 = 50 microM). DLXXL peptides were highly specific inhibitors of alphav beta6-fibronectin interaction as synthetic scrambled or reversed DLXXL peptides were inactive. NH2- and COOH-terminal modifications of the flanking amino acids suggested that the preceding two and a single trailing amino acid were also involved in interaction with alphav beta6. The DLXXL sequence is present in several matrix components and in the beta chain of many integrins. Although there is as yet no precise biological role known for DLXXL, it is clearly a specific inhibitory sequence for integrin alphav beta6 which has been unrecognized previously.

Amino Acid Sequence↗
PubMed1998

Regulation of the high affinity receptor for IgE on human epidermal Langerhans cells.

Human epidermal Langerhans cells (LC) express variable amounts of the high affinity receptor for IgE (Fc epsilonRI); the strongest expression is characteristic of atopic dermatitis. The receptor is suggested to take part in the pathophysiology of this disease by acting as a link between aeroallergens and Ag-specific T cells in an IgE-mediated, delayed-type hypersensitivity reaction. In the present study we show that even in the absence of surface expression, normal LC maintain an intracellular pool of the alpha-chain of Fc epsilonRI (Fc epsilonRIalpha) of the same m.w. as the surface-bound Fc epsilonRIalpha that is able to bind significant amounts of IgE. The lack of surface expression is linked to the absence or very low expression of the gamma-chain (Fc epsilonRIgamma). Moreover, the amount of Fc epsilonRIalpha expressed at the cell surface significantly correlates with the amount of Fc epsilonRIgamma. LC differentiation toward lymphoid dendritic cells is accompanied by the disappearance of transcripts for Fc epsilonRIalpha, but not for Fc epsilonRIgamma. This leads to a rapid decrease in the intracellular and surface levels of Fc epsilonRIalpha, which cannot be influenced by IL-4, IgE, or other agents. Overall, our findings suggest that these mechanisms enable LC to be highly versatile APCs by rapidly adapting the surface level of Fc epsilonRI to distinct inflammatory environments.

Cell Differentiation↗
PubMed1998

5-Lipoxygenase expression in Langerhans cells of normal human epidermis.

We studied expression of the 5-lipoxygenase (5-LO) pathway in normal human skin. In situ hybridization revealed a 5-LO mRNA-containing epidermal cell (EC) population that was predominantly located in the midportion of the spinous layer, in outer hair root sheaths, and in the epithelial compartment of sebaceous glands. Examination of skin specimens by immunohistochemistry and of primary ECs by flow cytometry mapped the 5-LO protein exclusively to Langerhans cells (LCs). The LC 5-LO protein was largely found in the nuclear matrix, in nuclear envelopes, and perinuclear regions as indicated by in situ confocal laser scan microscopy. Reverse transcription-PCR and immunoblot analyses of purified primary EC populations further indicated that LCs are major 5-LO expressing cells. Enriched primary LCs were also found to contain 5-LO activating protein (FLAP), leukotriene (LT) C4 synthase, and LTA4 hydrolase. By contrast, 5-LO, FLAP, and LTC4 synthase were undetectable or largely reduced, but LTA4 hydrolase transcripts and protein were identified in ECs depleted of LCs. These data show that naive LCs are major, and possibly the sole, 5-LO pathway expressing cells in the normal human epidermis.

Arachidonate 5-Lipoxygenase↗
PubMed1998

Is local intra-arterial fibrinolysis contraindicated in elderly patients with cerebral artery occlusion?

Local intra-arterial fibrinolysis (LIF) is an effective treatment for selected patients in acute thromboembolic occlusion of the middle cerebral artery, vertebrobasilar system or ophthalmic artery. However, the risk/benefit ratio of thrombolysis in patient subgroups requires classification. Advanced age has been regarded as a prognostic factor for poor clinical outcome. We report our experience with LIF in seven patients with a mean age of 79 years (range 76-83 years) who represented thromboembolic occlusion of the basilar, middle cerebral or pericallosal arteries. We discuss why advanced age need not contraindicate LIF.

Aged↗
PubMed1997

A small deletion of 16q23.1-->16q24.2 [del(16)(q23.1q24.2).ish del(16)(q23.1q24.2)(D16S395+, D16S348-, P5432+)] in a boy with iris coloboma and minor anomalies.

We report on a 5-year-old boy with bilateral coloboma of iris, short stature, moderate developmental delay, and a few minor craniofacial anomalies. High-resolution GTG banding showed a small distal deletion of one chromosome 16 [del(16)(q23.1q24.2)]. Molecular refinement of the deletion breakpoints yielded that the proximal breakpoint at 16q23.1 is located between loci D16S395 (present) and D16S348 (absent). Comparison with previously published cases of deletion 16q demonstrated that the clinical phenotype is not a recognizable 16q- syndrome and different from the two cases of deletions of 16(q22.1 to q24.1) described by Callen et al. [1993]. Evidently, deletion 16(q23.1q24.2) has a milder phenotypic effect than other interstitial and distal 16q deletions.

Child, Preschool↗
PubMed1997

Twenty-four-hour ambulatory blood pressure monitoring in young children.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has many advantages for the diagnosis and follow-up of hypertension at all ages. This technique has so far not been documented as applicable to the very young. We studied the feasibility of ABPM in 61 healthy children and in 40 patients with renal diseases and/or hypertension, aged less than 6 years. A satisfactory ABPM profile (recording time = 24 h and > 30 good recordings) was obtained in 77% of the healthy children. The mean number of good blood pressure (BP) measurements per 24 h increased with age from 46 (3-4 years) to 58 (6 years). The mean (+/- SD) systolic and diastolic BPs of healthy 3- to 6-year-old children (n = 47) were 110 +/- 5/67 +/- 5 mmHg during the day-time and 100 +/- 5/58 +/- 5 mmHg at night. In addition to the nocturnal decrease in BP, ABPM detected a second, day-time dip in BP during bed rest after lunch. Ninety percent of patients with renal disease and/or hypertension had successful ABPM recordings for 24 h, with an age-dependent increase in the mean number of reliable readings from 34 (< 2 years) to 48 (4 years). In 5 of 10 children with hypertensive results obtained by casual BP measurements, elevated BP was not confirmed by ABPM. We conclude that ABPM is a useful tool for the diagnosis and evaluation of hypertension in children under 6 years of age.

Aging↗
PubMed1996

Contrast letter thresholds in the non-affected eye of strabismic and unilateral eye enucleated subjects.

To investigate the effects of visual disruption on contrast letter thresholds of the non-affected eye, subjects with one eye enucleated, strabismic subjects using the non-deviating eye and normal control subjects were asked to identify letters on eye charts and single letter cards which varied in contrast (between 4 and 96%) and size. At all contrast, contrast letter acuity of eye enucleated subjects was superior to both normal control subjects and strabismic subjects. Early onset strabismic subjects (onset < 24 months) showed inferior performance to normal control subjects at all contrasts of 25% and above. Late onset strabismic subjects showed normal performance at all contrasts, except for high contrast single letters, where performance was inferior to normal control subjects. Further, for all subjects groups, performance on letter charts was similar to performance on single letter cards. We conclude that disruption to the visual system caused by eye enucleation or strabismus is not equivalent. These differences may be due to intrinsic differences between the visual systems of eye enucleated subjects and strabismic subjects and/or to the profound differences in deprivation caused by the two conditions.

Adolescent↗
PubMed1996

New insights in the structure and biology of the high affinity receptor for IgE (Fc epsilon RI) on human epidermal Langerhans cells.

The recent structural and functional analysis of the high affinity receptor for IgE (Fc epsilon RI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of Fc epsilon RI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical beta-chain. This also implies functional differences most probably related to the expression level. Although the signalling pathway seems to be similar to that of basophils or mast cells, LC from individuals with atopic dermatitis are fully activated by receptor ligation while LC from normal individuals fail to exhibit calcium mobilization under the same conditions. Finally, LC from normal and atopic individuals use Fc epsilon RI to maximize antigen uptake via specific IgE and subsequent presentation to T cells. Thus, Fc epsilon RI expressed on LC differs in terms of structure and function from that expressed on effector cells of anaphylaxis.

Antigen Presentation↗
PubMed1996

Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema.

We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (Fc epsilon RI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 neg population was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 dim, while the second population was CD1a dim/CD1b dim/Fc epsilon RI bright/CD23 dim/CD32 dim/HLA-DR bright/CD36 bright. The highest Fc epsilon RI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, Fc epsilon RI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of Fc epsilon RI in atopic eczema skin.

Antigens, CD1↗
PubMed1996

[Effect of intubation timing on the clinical course of polytrauma patients with lung contusions].

UNLABELLED: Aim of the study was to evaluate the influence of early intubation at the scene on the outcome of polytraumatized patients with lung-contusion. METHODS: 377 patients with lung-contusion out of 1031 polytraumatized patients were evaluated in this study. Patients, intubated at the scene were compared with those, who were intubated later. We compared the in-hospital time, the time at the ICU, the pneumonia-rate and the ARDS-rate. Age and injury severity of the compared groups were comparable. RESULTS: In-hospital time and time at the ICU were shorter in the early intubated group than in the later intubated (in-hospital time 34.5 d and 39.4 d, time at the ICU 19.9 d and 23.7 d, resp.). For the time at the ICU the difference is significant. Also a reduction was found in the pneumoniarates (23.7% and 13.2%). The ARDS rate was reduced, too, but both differences were not significant (ppneumonia = 0.053, pARDS = 0.117). The mortality also was not significantly reduced (23.4% and 22.7%, resp.). CONCLUSION: Early intubation at the scene can reduce the inhospital-time, the time at the ICU and the complications. In this way it becomes an important factor of cost-reduction. Therefore early intubation at the scene must become a standard for all patients with lung-contusion.

Adolescent↗
PubMed1995

DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor.

ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by instability of the pericentromeric heterochromatin predominantly of chromosomes 1 and 16. DNA methylation studies in two unrelated ICFS patients provide further evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific disturbances of chromatin structure take place within the satellite 2 DNA regions, as demonstrated by fluorescence in situ hybridization analysis. Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19 have revealed hypomethylation to different degrees in both patients; this provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell fusion experiments have revealed a distinct reduction of chromosomal abnormalities in ICFS cells after fusion with normal cells, suggesting that the abnormalities are caused by the loss of function of an as yet unknown trans acting factor. Although it is now clear that wide-spread DNA hypomethylation is a characteristic feature of ICFS, neither the cause and mechanism of hypomethylation nor their relationship to the clinical symptoms is known. We speculate that a phenotypic effect might result from tissue-dependent abnormal gene expression and/or from a possible structural disturbance of DNA domains, which, with respect to the immunodeficiency, partially prevents the normal somatic recombinations in immunologically active cells.

Cell Line, Transformed↗
PubMed1995

Alignment ability of strabismic and eye enucleated subjects on the horizontal and oblique meridians.

For normal sighted observers visual performance is often superior on the principal meridians than on the oblique. There has been no clear consensus on whether disruption of the visual system affects performance on orientation sensitivity tasks. Here we compare the abilities of normally sighted subjects tested monocularly, subjects with one eye enucleated and strabismic subjects using the non-deviating eye, in an orientation task. Subjects were asked to align a dot with a bar that was oriented either horizontally or on the oblique. For all groups, alignments were significantly more accurate and precise for the horizontal bar as compared to the oblique bar. Normally sighted subjects were significantly more precise on alignments in the horizontal and oblique planes than strabismic subjects, using the non-deviating eye. Precision for eye enucleated subjects was similar to that of normally sighted subjects. Precision of alignments did not correlate to the age at diagnosis of strabismus or to depth of amblyopia in strabismus. We conclude that for alignment ability, the disruption of visual development produced by enucleation of eye is not equivalent to that produced by strabismus. This could represent an underlying difference in the visual system between these two groups.

Adolescent↗
PubMed1993

Asymptomatic uveitis in children with chronic inflammatory bowel diseases.

Uveitis may be an asymptomatic ocular process when it occurs in association with chronic inflammatory bowel disease (IBD). However, the frequency of uveitis in pediatric IBD is not known, as few patients have eye examinations on a routine basis. Experience with a child with Crohn's disease, who had asymptomatic uveitis identified by routine screening initiated because of associated arthritis, prompted us to undertake this evaluation. The purpose of this cross-sectional prospective study was to ascertain the point-prevalence of uveitis in pediatric IBD patients, including 97 with Crohn's disease and 50 with ulcerative colitis. Each child underwent an ophthalmologic assessment, including slit-lamp examination. In Crohn's disease, inflammatory cells and/or flare were observed in the anterior chamber of six (6.2%) patients. These changes were mild in all six patients and required no treatment. In the group with ulcerative colitis, there were no cases of asymptomatic uveitis. There was a higher frequency of asymptomatic transient uveitis in patients with Crohn's colitis (four of 22, 18.2%) than in those of other anatomic subgroups (two of 75, 2.7%; p < 0.05). Frequency of uveitis was also higher in IBD patients having other extraintestinal manifestations (15.0%) than in those without (3.1%; p < 0.10). There was no relationship observed between the activity of bowel disease and presence of ocular inflammation.

Adolescent↗
PubMed1992

Detection of inspiratory resistive loads by heart-lung transplant recipients.

Human heart-lung transplantation recipients (HL) are models for the effects of selective lower respiratory tract denervation. We used a series resistor to examine thresholds of inspiratory flow resistance perception among 16 HL in comparison with 15 normal control subjects (C) and 12 heart transplant recipients (H). HL and C were closely age matched. H subjects were older and had mildly reduced lung volumes compared with the other groups. The perception threshold was defined as the added resistance (delta R) detected by subjects at 50% of random, blinded presentations. These delta R were subsequently expressed as a fraction of the airway resistance of the subject and baseline resistance of the apparatus (delta R/Raw + Rapparatus), otherwise known as the Weber fraction. The mean +/- SEM Weber fractions were nearly identical for HL and C (0.32 +/- 0.05 versus 0.34 +/- 0.05, respectively). The Weber fraction of H (0.74 +/- 0.17) was significantly greater than those of both other groups (p less than 0.05 by Kruskal-Wallis test). We conclude that lower respiratory tract afferents do not play a significant role in the perception of inspiratory resistive loads. The finding of an abnormally high Weber fraction in the heart transplant population remains unexplained but may be a function of age or restrictive pulmonary defects.

Adult↗