The interleukin-1-stimulated protein kinase that phosphorylates heat shock protein hsp27 is activated by MAP kinase.

In KB cells, interleukin-1 (IL-1), epidermal growth factor and phorbol ester transiently activated both MAP kinase and a serine kinase which phosphorylated the heat shock protein hsp27. Extracts made from IL-1-stimulated KB cells phosphorylated recombinant hsp27, in vitro, on serine residues 78 and 82 which are contained within Arg-X-X-Ser motifs similar to those phosphorylated by the ribosomal protein S6 kinases. Upon size exclusion chromatography, however, hsp27 kinase eluted as a single peak of activity at 50-60 kDa, clearly separated from ribosomal protein S6 kinases. Treatment of partially purified hsp27 kinase with protein phosphatase-2a reduced its activity by 80%. De-phosphorylated hsp27 kinase could be approximately 50% reactivated by a factor present in IL-1-treated cell extracts in the presence of ATP. This factor co-eluted with MAP kinase after partial purification by DEAE-cellulose, phenyl Sepharose, and size exclusion chromatography. Purified sea star p44mpk and recombinant ERK2 MAP kinases were also capable of re-activating hsp27 kinase to a similar extent. These data suggest that hsp27 kinase is downstream from, and probably a direct target of MAP kinase.

Evidence that MAP (mitogen-activated protein) kinase activation may be a necessary but not sufficient signal for a restricted subset of responses in IL-1-treated epidermoid cells.

We have investigated the activation of mitogen-activated protein kinase (MAP-kinase) in KB human epidermoid carcinoma cells treated with interleukin 1 (IL-1). MAP-kinase activity was transient; the time required for activity to reach a maximal level was dependent upon the dose of IL-1, ranging from 15 minutes to 45 minutes. The level of kinase induction correlated well with dose-response curves for two characteristic IL-1-induced responses, PGE2 and IL-6 production. MAP-kinase activity returned to basal levels within 2 hours regardless of the amount of IL-1 added to the system. Exposure of KB cells to free IL-1 was accordingly restricted to periods of 2 hours or less, by replacing IL-1 with an excess of IL-1 receptor antagonist. Even after 2 hours exposure, the ability of IL-1 to induce IL-6 or PGE2 was still IL-1ra-inhibitable by more than 80%, suggesting that events downstream of, or parallel to MAP-kinase activation, requiring the continual formation of new IL-1 receptor complexes, are needed to fully elicit these responses. Two general serine/threonine kinase inhibitors, K252a and quercetin, were found to strongly inhibit MAP kinase in vivo with ED50s of c. 100 nM and 30 microM, respectively. At these concentrations, both compounds effectively inhibited IL-1-driven PGE2 and IL-6 induction without affecting general protein synthesis or secretion. Other non-selective kinase inhibitors had less effect on MAP-kinase activation or IL-1-induced biological responses. The transient activation of MAP-kinase induction correlated strikingly with activation of the transcription factor NF-kappa B. IL-1-induced NF-kappa B activation was, however, relatively insensitive to inhibition by K252a or quercetin. We suggest that MAP-kinase is likely to be a necessary, but not sufficient, intermediate in some (IL-6, PGE2 induction) but not all (NF-kappa B activation) IL-1 responses in these cells.

[Clinico-experimental studies on the ability to drive in traffic after dental interventions]. / Klinisch-experimentelle Untersuchungen über die Verkehrstüchtigkeit nach zahnärztlichen Eingriffen.

Many psychophysical tasks important for driving performance were tested with an established battery of tests following routine treatment measures. The tested factors relevant for driving performance (e.g., reaction time, optomotor coordination, efficiency, concentration, fine motor control, optomotor functions) were not impaired following local anesthesia with Carticain, slightly impaired after "splinting with local anesthesia" and "operative removal of the third molar", and somewhat more impaired after "splinting without local anesthesia" (i.e., with pain). The reduction in performance however was considerably below that of test subjects with 0.8 0/00 and/or 0.5 0/00 blood alcohol concentrations. The legal significance of these results for the dentists was discussed.

[Studies on the surgical and chemotherapeutic management of oral cancer]. / Untersuchungen zur chirurgisch-chemotherapeutischen Behandlung des Mundhöhlenkarzinoms

Of the 101 patients who have been treated with bleomycin since 1971 two groups were formed: Group I: Preoperative chemotherapy with 345 mg bleomycin, followed by radical operation. Group II: 200 mg bleomycin preoperatively, followed by radical operation and postoperative chemotherapy up to a total dose of 345 mg bleomycin. 1. Bleomycin- induced cellular alterations showed a dose-time relation. 2. The treatment plan for group II with 200 mg bleomycin preoperatively plus postoperative cytostatic therapy up to a total of 345 mg resulted in less recurrences and fewer distant metastases than the sole preoperative application of the full dose of 345 mg bleomycin. 3. In all cases, preoperative microscopic examination after administration of the full dose of 345 mg still showed tumor cells with possible growth potential.

[Reconstructive surgery on the temporomandibular joint within the framework of oral rehabilitation]. / Rekonstruktive Eingriffe am Kiefergelenk im Rahmen der oralen Rehabilitation

After conservative functional therapy has failed, two operating methods are applied for oral rehabilitation: 1. Extraarticular bolting of the temporo-mandibular joint (indication: recurrent dislocation/habitual partial dislocation). 2. Reconstructive arthroplasty with a cartilage/bone graft (indication: loss or serious deformation of the mandibular condyle). Functional analysis with a detailed examining method showed a high rate of success with regard to improvement of function and freedom from symptoms.

[Growth of the jaw after preoperative orthodontic treatment of cleft lip and cleft palate]. / Untersuchungen über das Kieferwachstum bei präoperativer kieferorthopädischer Behandlung von Lippen-, Kiefer-, Gaumenspalten

In 48 patients a systematized therapeutic model plan for the preoperative and postoperative orthodontic treatment of patients with unilateral or bilateral cleft lips and palates is pursued. In addition to stimulation and growth control of the maxillary alveolar segments in a transverse direction and at the segment poles, increasing sagittal development is observed in a later developmental phase.