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Biomedical subjects

R Kaufmann

Publications and source records attributed to R Kaufmann.

At least 163 records · Page 9Linked to original sources
PubMed1997

Induction of psoriasiform inflammation by a bacterial superantigen in the SCID-hu xenogeneic transplantation model.

Psoriasis is a chronic skin disease affecting about 2% of the Caucasian population, characterized by co-existing inflammation and epidermal hyperproliferation. A T-lymphocyte-mediated autoimmune reaction induced by bacterial superantigens might be central in its pathogenesis. To model psoriasiform inflammation, we transplanted clinically uninvolved skin from psoriatic patients onto SCID mice. Repetitive intradermal injections with a bacterial superantigen and simultaneous intraperitoneal injections with the patients superantigen-stimulated peripheral mononuclear blood cells resulted in an inflammatory reaction exhibiting some of the hallmarks of psoriasis, e.g. epidermal hyperproliferation, papillomatosis, focal neo-expression of ICAMI, and an exocytotic T-lymphocytic infiltrate characterized by the expression of the cutaneous lymphocyte-associated antigen. These observations document the potential of superantigens to trigger psoriasiform dermatitis and provide a model to study lymphocyte homing.

Animals↗
PubMed1997

Superantigens but not mitogens are capable of inducing upregulation of E-selectin ligands on human T lymphocytes.

Bacterial infections can exacerbate immune mediated dermatoses, possibly via superantigens produced by these bacteria. Therefore, we asked whether superantigens induce the expression of adhesion molecules which may then facilitate invasion of highly activated T cells into different organs. The influence of exfoliative toxin (ET) and toxic shock syndrome toxin-1 (TSST-1) stimulation on the expression of a broad panel of adhesion and costimulatory molecules was investigated by flow cytometry. We found that only the E-selectin ligands cutaneous lymphocyte-associated antigen (CLA) and sialylated Lewis(x) (CD15s) are significantly upregulated by these superantigens but not by mitogen stimulation. In contrast, the mucosal lymphocyte-associated antigen (MLA) recognized by the monoclonal antibody Ber-Act8 was not differentially induced by mitogen or superantigen stimulation. Therefore, T lymphocyte stimulation by bacterial superantigens might directly influence their skin homing capacity. Furthermore, the superantigen-driven induction of CD15s-an adhesion molecule which is absent or only weakly expressed by resting or mitogen stimulated T cells-may indicate a role of this antigen for T cell skin homing. An additional adhesion pathway via E-selectin may thus be available to lymphocytes, comparable to granulocytes which constitutively express CD15s.

Antigens, CD↗
PubMed1997

Leg ulcers in Klinefelter's syndrome--further evidence for an involvement of plasminogen activator inhibitor-1.

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor-1 (PAI-1), has been recently documented in patients suffering from Klinefelter's syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI-1 activity is a general feature of Klinefelter's syndrome, or more specifically associated with leg ulceration, we investigated PAI-1 influencing parameters and PAI-1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n = 7); and (ii) Klinefelter patients without leg ulceration (n = 6). On analysing PAI-1 influencing parameters such as age, body mass index, triglycerides, C-reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and arterial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI-1 activity in group 1 was highly significantly elevated compared with that in group two patients (P < 0.005). We conclude that (i) PAI-1 activity is not elevated in Klinefelter's syndrome in general; (ii) elevation of PAI-1 activity in patients suffering from Klinefelter's syndrome does not appear to be secondary to PAI-1 influencing parameters; and (iii) elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter's syndrome. Therefore, a therapy for leg ulceration in Klinefelter's syndrome that aims to return the elevated PAI-1 activity to normal should be explored.

Arterial Occlusive Diseases↗
PubMed1997

[Simultaneous use of different nuclear medical examinations in Klippel-Trenaunay syndrome--vs. Proteus syndrome].

A three-year-old male patient presented already at his birth a disproportion macrosomia of the left foot and a large, nodular nevus flammeus in the left hip region, which led to the tentative diagnosis of a Klippel-Trenaunay syndrome. In the following years, both changes showed a continuous progression, with distinct soft-tissue swelling as well as papillomatous and verruciform vegetations of the nevus. Additionally, large, plain subcutaneous masses developed under the right shoulder, and a macrodactyly of the first and second left toe could be observed. Although several examinations had been performed in the meantime, the tentative diagnosis could not be confirmed up to that time. On the occasion of a severe local infection in the hip region, which led to the consideration of a surgical therapy, a radionuclide lymphography, a blood pool scintigraphy including dynamic phlebography and ventriculography as well as a bone scintigraphy were performed. These examinations were done simultaneously at one day in order to avoid a longer period of immobilization. The findings led to the diagnosis of a large lymphangioma, which could be confirmed histologically after surgery. In consideration of all results, the basic disorder seems to be the rare proteus syndrome rather than a Klippel-Trenaunay syndrome.

Bone and Bones↗
PubMed1997

The transformation of pityriasis lichenoides chronica into parakeratosis variegata in an 11-year-old girl.

Parakeratosis variegata is a rare disorder with unknown aetiology. In a few cases it arises from benign skin diseases such as pityriasis lichenoides et varioliformis acuta (Mucha Habermann disease) or pityriasis lichenoides chronica. However, transformation into malignant diseases such as cutaneous T-cell lymphoma has been observed. We report an 11-year-old girl with a 10-year history of pityriasis lichenoides chronica now presenting with parakeratosis variegata. Analysis of skin infiltrating T cells showed clonally rearranged T-cell receptor gamma chains occurring with a frequency of more than 2%. This finding is compatible with the clinical observation of parakeratosis variegata transforming into a malignant T-cell disorder. We therefore suggest that patients suffering from parakeratosis variegata and other diseases such as pityriasis lichenoides et varioliformis acuta or pityriasis lichenoides chronica should be continuously monitored.

Child↗
PubMed1996

Signaling effects of alpha-thrombin and SFLLRN in rat glioma C6 cells.

Effects of thrombin on brain cells, including change of neurite outgrowth and astrocyte shape, are described, but the molecular mechanisms are unclear. We investigated the effects of human alpha-thrombin and a six amino acid thrombin receptor activating peptide (TRAP-6, SFLLRN) on [Ca2+]i, phosphoinositide hydrolysis, and protein kinase C in rat glioma C6 cells. Stimulation of C6 cells with both alpha-thrombin and TRAP-6 resulted in [Ca2+]i mobilization, [3H]Inositol phosphate response, and enhanced immunoreactivity of the protein kinase C (PKC) isoenzymes alpha, beta, gamma, delta, and epsilon. Results suggest that alpha-thrombin and TRAP-6 activate at least partially the same intracellular signaling pathways in rat glioma C6 cells, which is evidence for involvement of "tethered ligand" receptor in thrombin induced signaling in glioma C6 cells.

Animals↗
PubMed1996

Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.

In this paper, cholecystokinin (CCK) B-type binding sites were characterized with receptor binding studies in different human brain regions (various parts of cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellar cortex) collected from 22 human postmortem brains. With the exception of the thalamus, where no specific CCK binding sites were found, a pharmacological characterization demonstrated a single class of high affinity CCK sites in all brain areas investigated. Receptor densities ranged from 0.5 fmol/mg protein (hippocampus) to 8.4 fmol/mg protein (nucleus caudatus). These CCK binding sites displayed a typical CCKA binding profile as shown in competition studies by using different CCK-related compounds and non peptide CCK antagonists discriminating between CCKA and CCKB sites. The rank order of agonist or antagonist potency in inhibiting specific sulphated [propionyl-3H]cholecystokinin octapeptide binding was similar and highly correlated for the brain regions investigated as demonstrated by a computer-assisted analysis. Therefore it is concluded that CCKB binding sites in human cerebral cortex, basal ganglia, cerebellar cortex share identical ligand binding characteristics.

Adult↗
PubMed1996

Analysis of carotenoids and carotenol fatty acid esters by matrix-assisted laser desorption ionization (MALDI) and MALDI-post-source-decay mass spectrometry.

Matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry and MALDI post-source-decay (PSD) fragment ion mass analysis were employed to examine various model carotenoids and some of their fatty acid esters. It was demonstrated that the use of MALDI helps overcome problems resulting from the inherent thermal instability and lack of solubility which render this group of compounds rather difficult for conventional ionization techniques. Detection limits were in the subpicomolar range. Rather abundant metastable fragmentation occurred under conditions of prompt extraction, but was significantly restricted under conditions of delayed extraction (DE). In DE the quasimolecular ion signals (mainly as odd electron radical ions) became the base peak even in spectra of the most delicate fatty acid esters. PSD fragment ion patterns were similar to those recorded under linked B/E scanning in conventional fast atom bombardment-MS and contained information on structural end group substituents such as hydroxyl, epoxide, or carbonyl functions and on the extent of double bond conjugations. The mono- and bis-fatty acid esters fragmented mainly by simple fatty acid cleavage but also furnished some of the end group-specific fragments.

Carotenoids↗
PubMed1996

[Results of treatment of multiple trauma in 130 children].

Trauma remains the leading cause of death in the pediatric age group, despite recent advances in prevention and treatment. We retrospectively analyzed 130 cases of multiple trauma among 725 pediatric patients with injuries treated here during 1988-1989. Road accidents and falls from heights were the most common causes of injury. Mean age was 7 years (range 0.5-15) and the male to female ratio 2.7:1.0. Overall mortality was 9.2%. 57 patients (44%) did not get any prehospital medical care and 5 of them with injury severity scores (ISS) greater than 25 died. In contrast 11/18 (61%) of patients with ISS greater than 25 who were treated by medical teams survived. On arrival at the emergency room, 15% were hypothermic ( < 34 degrees C), and 6 were in hypovolemic shock--5 of whom died. Most common injuries were head trauma (91), limb injuries (69), abdominal trauma (34) and thoracic trauma (34). In 39 injury was severe, with pediatric trauma score (PTS) 6 or less, 12 of whom died. All deaths except 1 were associated with severe head injury and with ISS more than 25. There was no mortality in those with PTS more than 7 or ISS less than 25. Thus, the prehospital care of pediatric patients with head injury is associated with high mortality. Absence of mortality in patients with PTS of more than 7 emphasizes the importance of designated trauma centers for these patients.

Adolescent↗
PubMed1996

Pulsed Erbium:YAG laser ablation in cutaneous surgery.

BACKGROUND AND OBJECTIVE: Among the various pulsed midinfrared-lasers studied in skin surgery the 2.94 microns Erbium:YAG laser has been shown to combine most efficacious ablation with least thermal damage due to its unique absorption characteristics in tissue water. A newly developed high-power Erbium:YAG laboratory laser providing output energies (up to 1.5 J/pulse) and repetition rates (up to 15 Hz) appropriate for clinical use enabled us to investigate its potential indications in dermatological surgery. STUDY DESIGN/MATERIALS AND METHODS: Erbium:YAG laser ablation was performed in vitro on pig skin and in vivo on a total of 30 patients presenting with different skin disorders. RESULTS: In vitro ablation efficiency linearly increased with radiant exposure and was inversely correlated with pulse frequency. Ablation rate at 10 Jcm-2 (used clinically) measured from approximately 10 microns (at 10 Hz) to 40 microns (at 1 Hz). Also for high repetition rates thermal necrosis did not exceed 50 microns, corresponding clinically to capillary bleeding after exposure of the dermis. Superficial lesions, such as epidermal nevi, were easily ablated and re-epithelization was unimpaired owing to the absence of tissue necrosis. In tattoos, exposed pigment particles were precisely removed. However, in deeper lesions the casual onset of bleeding impeded the procedure and scar formation was observed after reepithelization. CONCLUSION: Pulsed 2.94 microns Erbium:YAG laser surgery allows an extremely precise etching of delicate superficial skin lesions and also should have a potential for skin resurfacing.

Animals↗
PubMed1996

Comparison of sensitivity towards photodynamic therapy of cutaneous resident and infiltrating cell types in vitro.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) combines photosensitizers absorbing light in the visible spectral region and irradiation with light of corresponding wavelengths. We analysed the sensitivity of cell lines established from resident cutaneous cells and from transformed lymphocytes towards PDT. STUDY DESIGN/MATERIALS AND METHODS: PDT was performed employing either 630 or 662 nm light or polychromatic red light (600-700 nm) and photosensitizers Photosan-3, delta-aminolevulinic acid, or methylene blue. Proliferation measured by 3H-TdR uptake was determined in human immortalized keratinocytes (HaCaT) and mouse fibroblasts (NIH/3T3) in comparison to human transformed T-(HuT78) and B-lymphocytes (RA1). Additionally, uptake of the photosensitizers was estimated employing video-intensified fluorescence-microscopy (VIFM). RESULTS: Depending on the photosensitizer tested HaCaT and NIH/3T3 exhibited an ED50 up to 10-fold as high as the lymphocytic lines. Polychromatic red light was at least as effective at inducing photodynamic reactions as 630 or 662 nm light. VIFM revealed a positive correlation between sensitivity of a given cell type towards PDT and uptake of the photosensitizers. The differential uptake observed in vitro was confirmed in vivo: A photosensitizer applied topically on a lesion of a patient with mycosis fungoides was found to accumulate preferentially in the lymphocytic infiltrate. CONCLUSION: Selective topical polychromatic PDT seems to be a feasible goal for the treatment of cutaneous lymphomas.

Aminolevulinic Acid↗
PubMed1996

Post-source decay and delayed extraction in matrix-assisted laser desorption/ionization-reflectron time-of-flight mass spectrometry. Are there trade-offs?

By the incorporation of delayed extraction (DE) into matrix-assisted laser desorption/ionization time-of-flight mass spectrometry a dramatic improvement of performance with respect to sensitivity, mass resolution and mass accuracy of precursor ions up to approximately 10 kDa has been achieved. Since DE reduces collisional in-source activation to a large extent, the rate of subsequent metastable decay is considerably reduced. Results are presented which demonstrate that under DE the loss of total post-source decay (PSD) fragment ion yield can be as large as one order of magnitude but that, in terms of sensitivity, part of this loss is balanced by a better S/N ratio which results from a significantly improved mass resolution of the PSD fragment ions (M/delta M up to 1800 compared with M/delta M = 200-500 under prompt extraction). While this compensatory effect is true for the middle to high mass range of PSD fragment ions, it gradually vanishes towards the low mass end of the PSD mass scale where, in the case of linear peptides some important information (immonium ions) is lost. It appears, however, that in the majority of practical PSD work, DE improves the qualty of the PSD spectra and that high energy collisional post-source activation can compensate for the occasional loss of analytical information.

Amino Acid Sequence↗
PubMed1996

[Photodynamic therapy at the threshold of clinical use in disseminated dermatoses].

Photodynamic therapy (PDT) involving the sequential administration of photosensitizing drugs and light has a successful record in the treatment of superficial tumors. Recent investigations document not only cytotoxicity but also immunomodulatory effects of PDT. Cell type as well as state of activation and differentiation are among the parameters influencing susceptibility to PDT, thus allowing targeting of selected cell (sub-)populations. In addition to lasers, non-coherent light sources are also effective. These features, along with current clinical experience, suggest PDT as an interesting alternative to better established photochemotherapies in the treatment of widespread malignant and benign dermatoses.

Humans↗
PubMed1996

The superantigen exfoliative toxin induces cutaneous lymphocyte-associated antigen expression in peripheral human T lymphocytes.

Several immune-mediated dermatoses including psoriasis and atopic dermatitis can be exacerbated by bacterial infections. Superantigen producing bacteria can be isolated from skin lesions of these dermatoses. Consistent with superantigen effects, skewed T cell receptor variable gene usage has been demonstrated within these lesions. Therefore, the question arises whether superantigen induce a skin-seeking phenotype within peripheral T cells. In this study, we investigated the in vitro influence of the V beta 2-selective superantigen exfoliative toxin from Staphylococcus aureus on the expression of the cutaneous lymphocyte-associated antigen on peripheral T lymphocytes of healthy donors. We demonstrate that exfoliative toxin dramatically upregulates cutaneous lymphocyte-associated antigen expression on T cell receptor V beta 2+ lymphocytes. Up to 69% of V beta 2+ lymphocytes expressed cutaneous lymphocyte-associated antigen after 5 days of in vitro culture. Additionally, exfoliative toxin also increased cutaneous lymphocyte-associated antigen expression in CD3+ T cell receptor V beta 2- lymphocytes indicating a different effect as caused by the superantigen-T cell receptor V beta 2 interaction. Our findings suggest influence of bacterial superantigens on T lymphocyte skin homing in vivo.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1996

Adverse reactions to local anesthetics: analysis of 197 cases.

BACKGROUND: Adverse drug reactions to local anesthetics are frequently reported. However, little is known about the underlying mechanisms. Therefore we investigated 177 patients with a history of 197 events after application of these drugs. METHODS: The diagnostic approach included prick and intracutaneous tests, provocative challenge tests with causative and unrelated local anesthetics, and in selected cases, radioimmunoassays to detect specific IgE. In addition, tests were performed with preservatives, including sodium metabisulfite and parahydroxybenzoic acid ester. RESULTS: Results of prick and intracutaneous tests with local anesthetics were all negative. Only three patients reacted after subcutaneous challenge with the causative drug (local anesthetics of the amide type). Although one patient showed a delayed-type response to mepivacaine, two patients had immediate-type reactions to articaine and lidocaine. However, in both cases no specific IgE could be detected. In five patients with positive skin test reactions to preservatives, challenge test results remained negative. CONCLUSION: Two immediate-type reactions were not IgE-mediated. In only one of 197 reported adverse reactions were we able to prove delayed-type allergic response. Therefore true allergic reactions caused by local anesthetics are extremely rare.

Administration, Oral↗
PubMed1996

Employee drug use, demographic characteristics, work reactions, and absenteeism.

Employees in a large work organization participated in an investigation of relationships between drug use and absenteeism and tardiness. Specifically, the study investigated the extent to which both self-reported and urine-screened drug use accounted for variance in several types of absenteeism, as well as tardiness, above and beyond that accounted for by demographic and work reaction variables. The results showed that employee drug use accounted for additional statistically significant variance in overall absenteeism and in absenteeism due to injuries and suspensions, as well as days tardy. Implications of these findings for organizational drug testing are discussed.

Absenteeism↗