Laboratory diagnosis of 24 cases of human cytomegalovirus (HCMV) infection in patients with the acquired immunodeficiency syndrome, renal transplant recipients and premature infants was achieved. These results were obtained by a rapid, sensitive and versatile HCMV-antigen detection method, which combined cell culture and immunoperoxidase staining with a monoclonal antibody to an HCMV "early" nuclear protein. The results were compared with HCMV isolation by the conventional cell culture method. While some of these immunocompromised patients lacked a significant antibody response, infective HCMV could be detected in the patients' urine and bronchial lavage fluid. The diagnostic procedure took no longer than 24 h. The usefulness of this antigen test for an effective diagnosis in immunocompromised individuals was demonstrated. We recommend routine analysis of various specimens, since recent developments in chemotherapy of HCMV infection and the risks of long-term damage demand immediate management of the patients concerned.

Adult↗

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[Rupture of the pectoralis major muscle: classification of injuries and results of operative treatment].

AIM: Classification of pectoralis major muscle injuries and results of operative treatment in the Sportsklinik Stuttgart between 1998 and 2004 are analysed. METHODS: 10 sportsmen (2 judo, 8 body-building; 9 male, 1 female) with pectoralis major ruptures received operative treatment in this time period. After clinical examination we used ultrasound, in some cases MRI, for further diagnostics. The follow-up (1-5 years) included a clinical examination, ultrasound, sports level, cosmetics and an isokinetic strength assessment. RESULTS: In 4 cases we found a tear of the musculotendinous junction, 4 cases showed a tear at the humeral insertion and 2 other cases had tears of the muscle belly. There was no sports-specific injury. 6 ruptures underwent immediate (1 week) operative therapy and 4 ruptures had delayed (6 weeks to 4 years) repair of the injury. In 9 cases an anatomic repair was possible, in 1 delayed rupture only an extra-anatomic repair was possible. We had 1 complication with a post-operative wound infection. Based on injury localisation and operative treatment, we classified 3 types of pectoralis major ruptures. The follow-up evaluation showed in 7 cases very good and good results, 2 delayed cases still had a cosmetic defect with reduction of strength. CONCLUSION: From our results on pectoralis major muscle injuries there are 3 types of rupture: type 1: rupture at humeral insertion, type 2: rupture of musculotendinous junction, type 3: rupture of muscle belly. This classification is essential for planning the operative technique and the incision. We recommend, after classification of the rupture, primary operative reconstruction of the pectoralis major muscle.

Adult↗

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Optical visualization of polymer-polymer interactions.

Surface-enhanced absorption (SEA) has been used to monitor interactions of biomolecules and to observe structural changes of polymers. Such interactions of biomolecules are of interest in high-throughput screening and diagnostics. The structural changes of synthetic polymers can be exploited in optical sensorics. Based on SEA we have developed a technique that enables us to transfer the interaction of polyelectrolytes between two flat, solid surfaces into a visible color change, exploiting nanoscopic metal clusters. The polyelectrolytes are coated onto electrochemically oxidized aluminum, glass, and polycarbonate substrates. The change of surface color is monitored with a flat-bed scanner, and the interactions are analyzed kinetically. The results are interpreted with regard to adhesion, surface tension, electrostatic interactions, and miscibility.

Colorimetry↗

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[Pump-gun as a weapon. Type of injuries, prohibition of weapons].

Pumpguns are shotguns with pump action whose injuries and wound mechanisms have several special features: extremely high kinetic energy of the shot (2500 to 3500 J) frequent cases of "Krönlein shots" (exenteration of the brain) punchmark/imprint immediately adjacent to the entrance wound from the front of the pipe magazine exit wounds from buckshot may be similar to pellet entrance injuries from a distant shotgun discharge the use of various shotgun cartridges (plastic ammunition, slug bullet, various lead pellets) within the same weapon. The change in the Austrian gun law and the banning of the pumpgun in 1995 is also discussed in the article.

Adult↗

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Intercellular induction of apoptosis through modulation of endogenous survival factor concentration: a review.

Fibroblasts constitutively express a functional apoptosis machinery which is under negative control by operationally defined endogenous survival factors. Oncogenic transformation causes a marked downmodulation of endogenous survival factor concentration which renders transformed cells more sensitive to various apoptosis stimuli compared to their nontransformed counterparts. Endogenous survival factors can be inactivated by reactive oxygen species (ROS). Endogenous survival factors are the ultimate targets for apoptosis-inducing factors derived from TGF-beta-triggered nontransformed cells during intercellular induction of apoptosis. During this control step of oncogenesis, endogenous survival factors in transformed cells are inactivated by ROS and the apoptosis machinery is released from negative control. This mechanism leads to the specific elimination of transformed cells. Our data show that the transformed state causes both the ability of the cells to perceive the apoptosis-inducing signal and a decrease in the concentration of endogenous survival factors. These two mechanisms are of central importance for the regulation of intercellular induction of apoptosis.

Animals↗

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Three distinct roles for TGF-beta during intercellular induction of apoptosis: a review.

During intercellular induction of apoptosis, transformed fibroblasts are eliminated through the action of neighbouring nontransformed cells. TGF-beta thereby plays three distinct and central roles. a) TGF-beta released by transformed cells or added exogenously to the assay system triggers nontransformed cells to release a shortlived apoptosis inducing factor, which is specifically directed against transformed cells. b) TGF-beta is involved in the maintenance of the transformed state, which is required for expression of sensitivity for intercellular induction of apoptosis. c) TGF-beta further sensitizes transformed cells through downmodulation of their endogenous survival factors, which control a constitutively expressed apoptosis machinery. These data demonstrate that TGF-beta which is utilized by transformed fibroblasts for the maintenance of their transformed state, causes recognition of transformed cells by their nontransformed neighbours and triggers and enhances an apoptosis-inducing response which finally causes elimination of potential tumor cells.

Animals↗

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How can tumor cells escape intercellular induction of apoptosis?

A novel concept for the control of oncogenesis has been established for fibroblasts. Transformed fibroblasts are subject to intercellular induction of apoptosis by TGF-beta or FGF-triggered nontransformed neighboring cells. If this control system acts in vivo as efficiently as it does in vitro, tumor formation should require the establishment of resistance mechanisms directed against intercellular induction of apoptosis. In line with this hypothesis, ex vivo tumor cells have been recently shown to be resistant to intercellular induction of apoptosis, whereas cells transformed in vitro and not passaged in an organism were regularly sensitive. Based on the knowledge of signaling between transformed and nontransformed cells during intercellular induction of apoptosis, several possible mechanisms for resistance of tumor cells are summarized in this paper.

Apoptosis↗

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Ex vivo tumor cell lines are resistant to intercellular induction of apoptosis and independent of exogenous survival factors.

Elimination of transformed fibroblasts through intercellular induction of apoptosis has been postulated as representing an efficient control step during oncogenesis. Whereas fibroblasts transformed by chemical carcinogens in vitro were sensitive to intercellular induction of apoptosis, ex vivo tumour cells derived from animals treated with chemical carcinogens were resistant to this control step. Resistance was achieved through two different mechanisms. Two cell lines overexpressed endogenous survival factors and thus the action of intercellular signalling (ICS) was not sufficient for complete depletion of endogenous survival factors. One of the resistant ex vivo tumour lines contained the same concentration of endogenous survival factors as its in vitro transformed and sensitive counterpart, but the endogenous survival factors were protected from the action of ICS in the resistant tumour cell line. In addition, the ex vivo tumour cell lines showed a marked independence of exogenous survival factors. Our data indicate that tumour formation requires independence of control by neighbouring cells and by exogenous survival factors.

Animals↗

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Selective effect of tumor necrosis factor on transformed versus nontransformed cells: nonselective signal recognition but differential target cell response.

TNF treatment causes oxidative down-modulation of endogenous survival factors in transformed as well as nontransformed fibroblasts. Endogenous survival factors are negative regulators of a constitutively expressed apoptosis machinery and have been defined in several cellular systems. As transformed cells harbour lower concentrations of endogenous survival factors than nontransformed parental cells, TNF-dependent down-modulation of endogenous survival factors in transformed cells is sufficient to release the apoptosis machinery from negative control and to cause cell death. In contrast, in nontransformed cells, due to their higher initial concentration of endogenous survival factors, down-modulation by TNF is not complete and therefore apoptosis is still prevented. Our data showed that perception of TNF signalling is not different between transformed and nontransformed cells, but that their differential response is due to quantitative differences in their regulatory setup. Furthermore, our data explained why application of low concentrations of cycloheximide can sensitize cells for apoptosis induction by TNF-alpha.

Animals↗

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Synergistic action between tumor necrosis factor-alpha and transforming growth factor type-beta: consequences for natural antitumor mechanisms.

TNF-alpha and TGF-beta are central signal molecules for natural antitumor mechanisms. Our data demonstrated that both factors act synergistically during apoptosis induction in transformed cells. This interaction of the two factors may have biological consequences for the efficiency of natural antitumor systems: 1) Transformed cells pretreated with TNF-alpha could be eliminated more efficiently by neighbouring nontransformed cells during intercellular induction of apoptosis; 2) TGF-beta pretreatment of transformed cells night sensitize them for apoptosis induction by macrophages. These findings allow three major conclusions: 1) Endogenous survival factors seem to be central regulatory elements for different apoptosis-inducing systems: 2) Macrophages and intercellular induction of apoptosis should be able to act in a synergistic way during the control of oncogenesis; 3) Resistance against one of the two mechanisms might cause resistance against the other as well.

Animals↗

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Reactive oxygen and nitrogen species: efficient, selective, and interactive signals during intercellular induction of apoptosis.

During intercellular induction of apoptosis, transformed fibroblasts are specifically eliminated by their nontransformed neighbours. This potential control step of oncogenesis is based on a sophisticated system of interdependencies and interactions of reactive oxygen and nitrogen species. Activated nontransformed effector cells release a novel peroxidase and nitric oxide. Superoxide anions generated extracellularly by transformed cells participate in intercellular signalling and also determine transformed cells as selective targets for intercellular induction of apoptosis. The interaction of these molecules results in two major signalling pathways, which are based on HOCl/hydroxyl radicals and on NO/peroxynitrite. In addition, involvement of nitrylchloride seems to be conceivable in an alternative pathway. Hydrogenperoxide plays a central and ambivalent role by fostering the HOCl/hydroxyl radical pathway and by inhibiting the NO/peroxynitrite pathway. The interaction of ROS and RNS during intercellular induction of apoptosis seems to represent a general signalling concept utilized by several natural antitumor systems.

Apoptosis↗