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Biomedical subjects

M Lukas

Publications and source records attributed to M Lukas.

7 recordsLinked to original sources

Migration of langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF-alpha and IL-1beta.

Migration from sites of antigen encounter to lymphoid organs is essential to the strong immunogenic function of dendritic cells (DC). In the skin, migration proceeds through dermal lymphatic vessels and is regulated in an incompletely understood way by inflammatory mediators. We studied the effects of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in mouse skin organ cultures by direct enumeration of migrating DC and by immunohistochemistry. (1) Neutralizing antibodies to TNF-alpha and IL-1beta inhibited migration of DC, also in human skin explants (TNF-alpha). (2) TNF-alpha at low concentrations (50 U/mL) and IL-1beta (50-3000 U/mL) augmented migration to about 150% of spontaneous migration. (3) High concentrations of TNF-alpha (5000 U/mL) inhibited migration by approximately 50%. (4) DC migration from skin explants of TNF-alpha/lymphotoxin-alpha double-deficient mice and TNF-receptor type 1 and 2 double knockout mice was not impaired. (5) TNF-alpha effects were neutralized by anti-IL-1beta, and vice versa. We conclude that in normal animals both TNF-alpha and IL-1beta are required for DC migration to occur. In the complete absence of one cytokine (TNF-alpha), however, backup mechanisms step in.

Animals

Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model.

The capacity to migrate from peripheral tissues, where antigen is encountered, to lymphoid organs, where the primary immune response is initiated, is crucial to the immunogenic function of dendritic cells (DC). The skin is a suitable tissue to study migration. DC were observed to gather in distinct nonrandom arrays ("cords") in the dermis upon culture of murine whole skin explants. It is assumed that cords represent lymphatic vessels. Using a similar organ culture model with human split-thickness skin explants, we investigated migration pathways in human skin. We made the following observations. 1) Spontaneous emigration of Langerhans cells took place in skin cultured for 1-3 d. Nonrandom distribution patterns of strongly major histocompatibility complex class II-expressing DC (cords) occurred in cultured dermis. A variable, yet high (>50%) percentage of these DC coexpressed the Birbeck granule-associated antigen "Lag." Ultrastructurally, the cells corresponded to mature DC. 2) Electron microscopy proved that the dermal structures harboring the accumulations of DC (i.e., cords) were typical lymph vessels. Moreover, markers for blood endothelia (monoclonal antibody PAL-E, Factor VIII-related antigen) and markers for cords (strong major histocompatibility complex class II expression on nonrandomly arranged, hairy-appearing cells) were expressed in a mutually exclusive pattern. 3) On epidermal sheets we failed to detect gross changes in the levels of expression of adhesion molecules (CD44, CD54/ ICAM-1, E-cadherin) on keratinocytes in the course of the culture period. The reactivity of a part of the DC in the dermal cords with Birbeck granule-specific monoclonal antibody "Lag" suggests that the migratory population is composed of both epidermal Langerhans cells and dermal DC. We conclude that this organ culture model may prove helpful in resolving pathways and mechanisms of DC migration.

Cell Movement

[Collection and utilization of plasma in Austria: on the way to national self-sufficiency].

Self-sufficiency for plasma and plasma products on the basis of voluntary non-remunerated donation is more than guaranteed in Austria. Historically commercial enterprises are co-operating with the non profit sector of the Austrian Red Cross in an ideal way since more than 30 years. Austria needs about 16 millions IE of factor VIII yearly to treat the haemophilia patients as it should be. About 100,000 1 source plasma (FFP) coming from the industry and some 50,000 1 of frozen plasma per year being given for fractionation by the Red Cross Blood Transfusion Services seem to be sufficient for preparing the amount of factor VIII needed. Austria feels furthermore responsible to also fulfill its part as a member of the European Community in order to reach the common European goal of self-sufficiency in due time. As for the term "non remunerated' it is our strong concern that to compensate the plasma donor's time- and work-spending by reinbursement does not mean any sort of "payment'. We agree herewith with the opinion of the "Arbeitskreis Blut' in Germany. To change the successful way of having enough raw material to treat all our haemophilia patients with the necessary amounts of factor VIII by abruptly and artificially pressing for unpaid plasma donations would be a bad decision. By certainly not getting enough plasma by using such an unusual way this idea would not be successful. Austrian Red Cross does not intend to create own plasmapheresis-centres.

Austria

[Comprehension of metaphoric speech by healthy probands and schizophrenic patients. An experimental psychopathologic contribution to concretism].

The comprehension of auditorily presented sentences with a metaphoric content was investigated in three experimental studies. Experiments 1 and 2 established the time course in control subjects: At 400 ms after prime offset only the concrete meaning was activated, whereas 1200 ms after prime offset both concrete and metaphoric meaning were active. Experiment 3 demonstrated a heightened activation of the concrete meaning and no activation of the metaphoric meaning in schizophrenic patients. These results resolve the dispute over the use of concepts by schizophrenic patients (overinclusive versus underinclusive), and can be related to the neurobiology of working memory and of associative semantic memory. The three experiments may serve as paradigms of how the method of mental chronometry can be applied in the field of psychopathology.

Adolescent

Correlations between verbal memory performance and electrocorticographically determined suppression of electrical brain activity in intracarotid amobarbital tests.

As a part of presurgical evaluation, bilateral intracarotid amobarbital procedures (IAPs) were performed in 42 patients (84 tests) with long-standing, medically intractable complex-partial seizures. During the IAPs, electrocorticographic (ECoG) recording was carried out via bilaterally implanted subdural electrodes. Five distinct patterns of suppression of electrical brain activity were observed: (1) an isoelectric line; (2) a burst-suppression pattern; (3) polyphasic waves; (4) high-voltage beta; and (5) low-voltage beta activity. Further, two types of specific reactions of the epileptic focus were detectable: (1) spike-burst-suppression patterns (SBS; 11 left; 7 right; 6 in both IAPs) and amobarbital-induced spikes (7 left; 4 right). ECoG suppression patterns as well as SBS and spike induction showed great variability in duration and overall occurrence. To determine the influence of these amobarbital-induced ECoG changes on results of IAP memory testing, performance in a verbal learning task was analyzed according to the ECoG patterns predominant during encoding. In left IAPs, it was found that SBS at the beginning of or during encoding had a significant negative effect on verbal memory. In right IAPs, verbal memory performance improved significantly with the decline of ECoG suppression. Hence, verbal memory performance in IAPs is significantly affected by specific ECoG suppression patterns and activation of the epileptic focus.

Adolescent