Biomedical subjects
Publications and source records attributed to G Sauer.
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The first consecutive 250 implantations of an uncemented, proximally anchored straight femoral shaft prosthesis (BiCONTACT) in 236 patients are included in this prospective follow-up study. Average time of follow-up evaluation was 8.9 years (range, 7.4-10.7 years). At follow-up, 27 patients had died, and 2 could not be located. Seven patients underwent revision-2 for infection, 1 for recurrent dislocation, 2 for component undersizing with rapid subsidence, and 1 for aseptic loosening of a varus-malaligned stem; 1 radiologically well-fixed stem had been revised during acetabular revision. Overall survival was 97.1% after 11 years (confidence limits, 98.7% [upper] and 93.6% [lower]). The average Harris Hip score at time of follow-up was 84.3 points. Radiologically, tiny reactive lines (<2 mm) were present in the distal zones of the femoral shaft, but no radiolucencies could be found in the proximal anchoring zone. The midterm to long-term follow-up results with the evaluated femoral component are encouraging and are comparable to those of modern techniques of cementing in primary total hip arthroplasty.
Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin as a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts. Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-associated vimentin kinases. We provide evidence for at least two Raf-1-associated vimentin kinases and identified one as casein kinase 2. They are regulated by Raf-1, since the activation status of Raf-1 correlated with the phosphorylation of vimentin. Vimentin phosphorylation by Raf-1 preparations interfered with its polymerization in vitro. A subset of tryptic vimentin phosphopeptides induced by Raf-1 in vitro matched the vimentin phosphopeptides isolated from v-raf-transfected cells labeled with orthophosphoric acid, indicating that Raf-1 also induces vimentin phosphorylation in intact cells. In NIH 3T3 fibroblasts, the selective activation of an estrogen-regulated Raf-1 mutant induced a rearrangement and depolymerization of the reticular vimentin scaffold similar to the changes elicited by serum treatment. The rearrangement of the vimentin network occurred independently of the MEK/ERK pathway. These data identify a new branch point in Raf-1 signaling, which links Raf-1 to changes in the cytoskeletal architecture.
Polarographic determination of tumor oxygenation by Eppendorf histography is currently under investigation as a possible predictor of radiotherapy outcome. Alternatively, the alkaline comet assay has been proposed as a radiobiological approach for the detection of hypoxia in clinical tumor samples. Direct comparisons of these methods are scarce. One earlier study with different murine tumors could not establish a correlation, whereas a weak correlation was reported for a variety of human tumors. Considering the different end points and spatial resolution of the two methods, a direct comparison for a single tumor entity appeared desirable. Anaplastic R3327-AT Dunning prostate tumors were grown on Copenhagen rats to volumes of 1-6 cm(3). Eppendorf histography (100-200 readings in 5 parallel tracks) for 8 different tumors revealed various degrees of oxygenation, with median pO(2) values ranging from 1.1 to 23 mmHg. Within 5 min after an acute exposure to 8 Gy (60)Co gamma rays, tumors were excised from killed animals and rapidly cooled to limit repair, and a single cell suspension was prepared for use with the comet assay. The resulting comet moment distributions did not exhibit two subpopulations (one hypoxic and the other aerobic), and a hypoxic fraction could not be calculated. Instead, the average comet moment distribution was taken as a parameter of overall strand break induction. Corresponding experiments with tumor cells grown in vitro allowed us to derive the relationship between the oxygen enhancement ratio (OER) for the average comet moment and oxygen partial pressure (Howard-Flanders and Alper formula). The validity of this relationship was inferred for cells exposed in situ, and the convolution of a pO(2) distribution with the formula of Howard-Flanders and Alper yielded an array of expected OER values for each tumor. The average expected OER correlated well with the average comet moment (r = 0.89, P < 0.01), and the in situ comet moment distributions could be predicted from the Eppendorf data when 50% repair was taken into account, assuming a 5-min damage half-life. The findings confirm the potential of interstitial polarography to reflect radiobiologically relevant intracellular oxygenation, but also underscore the confounding influence of differences in repair that may occur when cells are prepared from irradiated tissues for use with the comet assay.
According to Davis' (1965) model of the inner ear, a potential difference between the endocochlear potential and the hair cell resting potential drives the transduction current across the apical hair cell membrane. It is assumed that the endocochlear potential (EP) consists of two components. The first is a diffusion potential, which depends on the ionic composition of endolymph and perilymph and on the permeability of the perilymph-endolymph barrier. The second is an electrogenic component which is determined by active ion transport across the perilymph-endolymph barrier. In birds, the EP is between +8 and +20 mV. Little is known about the underlying mechanisms responsible for the measured EP in birds. The present paper studies whether ionic compositions of endo- and perilymph might explain the EP in birds. Concentrations of Na+, K+, Ca2+ and Cl- in pigeon scala vestibuli, scala tympani and scala media were determined with ion-selective microelectrodes. Na+, K+, Ca2+ and Cl- were 150.0, 4.2, 1.4 and 117.0 mM in perilymph (scala tympani and scala vestibuli). In scala media, the concentrations of K+, Ca2+ and Cl- were 140.6, 0.23 and 142.1 mM.
The adhesion of tumor cells to various extracellular matrix (ECM) proteins is influenced by epidermal growth factor (EGF). Maximal effects are obtained at low EGF concentrations, at which mostly the cytoskeleton-associated high-affinity EGF receptors (EGFRs) are saturated. Tumor cells expressing EGFR either endogenously (MDA MB 231, MTLn3) or, for the human EGFR, ectopically (MTC HER1/1) in intermediate amounts exhibited, upon EGF addition, increased cellular adhesion to various ECM proteins, such as fibronectin, collagens and vitronectin. In contrast, human A431 and MDA MB 468 cells, over-expressing EGFR, demonstrated reduced attachment in similar experimental conditions. Both increased as well as reduced EGF-dependent adhesion could be blocked using either ligand-blocking monoclonal antibody 14E1 or the potent EGFR tyrosine kinase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on cellular adhesion since both can be prevented by EGFR inhibition. Thus, the integration of EGFR- and integrin-dependent signals can be different in carcinoma cell lines and might be influenced by EGFR numbers.
The German Society for Cardiac Angiography and Interventions in Private Practice has started a registry of cardiac procedures since 1996 in order to establish a standard for performance. Although quality management for the cath lab makes sense and is also legally required, there is no generally recommended infrastructure for quality assurance existing in Germany at this time. Therefore, the German Society of Cardiologists in Private Practice (BNK) initiated a project in 1994 to develop a computer program for paperless documentation of diagnostic cardiac catheterizations and coronary interventions (PTCA) using a minimal data set. In 1996, 8 private associated groups participated in this project. The (anonymous) analysis of 10,316 diagnostic cardiac catheterizations and 2597 PTCA yielded the following results: In 95% of the patients, diagnostic cardiac catheterization was performed using the femoral and in 5% the brachial/radial approach. The mean volume of administered contrast medium was 164 +/- 138 ml/patient. The mean LV-EF was greater than 50% in 58.4% of the patients and between 30% and 50% in 10.1%. Coronary artery disease was diagnosed in 69.6% of the patients and valvular/congenital heart disease in 8.5%. In 18.4% of the patients undergoing diagnostic cardiac catheterizations no significant heart disease was identified. Mortality in the cath lab as well as the rate of cerebral insults was 0.05%. In 22.9% and 19% of the patients PTCA and cardiac surgery respectively was recommended. In patients undergoing PTCA, stable angina was present in 74.4% and unstable angina in 13.1%. Of the total number of PTCA procedures, 5.8% were performed in the setting of acute myocardial infarction. The PTCA lesion success rate was 96%, the mean diameter stenosis was 81% pre and 6% post-intervention. The mortality rate at 1 month post-PTCA was 0.4%, and myocardial infarction 1.0%. An acute occlusion occurred in 1.3% of the PTCA patients; 0.6% had to be transferred for emergency bypass surgery. None of the cath labs had on-site surgery. In comparison to other registries, our data show some similarities but also some different trends. Thus, our newly developed software proved to be reliable, fast and easy to use. Participating centers receive immediate feedback regarding their position within the whole group.
Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse on Oral Problems related to HIV infection and the WHO Collaborating Centre on Oral manifestations of the immunodeficiency virus, were studied in 600 consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%, hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those reported elsewhere, but socio-cultural differences allowed no reliable comparison. More than a quarter of our patients had oral soft tissue discomfort necessitating treatment; in 3.3% these were the presenting symptom. This indicates a potential major public health concern requiring education in recognition and appropriate referral and management.
Little is known about inner ear development in pigeons. This paper addresses the question of maturation in activity patterns of pigeon auditory nerve fibres, Pigeons that were 1, 2 and 4 weeks and 1, 2, 3 and 4 years old were investigated. Adult-like activity patterns are found 4 weeks post-hatching. Spontaneous activities of fibres in immature animals (about 40 spikes/s) are half that found in adults. Spontaneous discharge rate does not increase with decreasing characteristic frequency (CF) of the fibre if the animals are immature. Rate threshold are less sensitive in immature animals. Differences between the age groups are generally significant if the CFs of the fibres are below 1.3 kHz. Sharpness of tuning is already adult-like in l-week-old animals. Inter-spike time interval histograms (ISTH) of auditory fibres recorded in animals of all age groups often show Poisson-like distributions. Preferred intervals are found in 10% of the ISTHs of fibres in immature animals but in 30% of adults. Cross-correlations between heart beats of the animal and spontaneous activities show good correlation for about 70% of the fibres in immature animals. With the growth of the animals, the number of fibres showing correlation of spontaneous activities and heart beats decreases to about 40%. The basilar papilla of a 1-week-old animal is smaller than in an adult animal (by 10% in length and by 10% in width), judge by scanning electron microscopy (SEM), Changes of activity patterns in this study are likely to be a result of maturation of the middle ear. In addition to the latter, development of the inner ear is conceivable.
The reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose. Therefore, the killing mechanism of TNF under conditions of reduced glucose supply was investigated. Flow cytometry experiments and studies of kinetics revealed that the S-phase of the cell cycle was prolonged in the absence of glucose. After TNF treatment, the S-phase was found to be shortened and the rate of 3H-thymidine incorporation into DNA was increased, whereas EGF failed to exert such an effect. DNA synthesis and entry into mitosis are known to be regulated by cyclin A. In serum-starved tumor cells (HeLa) we have observed increased cyclin A synthesis within 10 hr, in parallel with enhancement of DNA synthesis and shortening of the S-phase after TNF treatment. We conclude that, under conditions of low glucose supply, TNF can assume the role of a growth factor in transformed cells.
In the presence of lauric acid (C12), the production of infectious vesicular stomatitis virus (VSV) was inhibited in a dose-dependent manner. The inhibitory effect was reversible; after removal of C12 the antiviral effect disappeared. In addition, the chain length of the monocarboxylic acids proved to be crucial, as those with shorter or longer chains were less effective or had no antiviral activity. Concomitant with the C12-induced inhibition was the stimulation of triacylglycerol synthesis, increasing the amount up to ninefold. Analysis of the antiviral mechanism of C12 revealed that the correct assembly of the viral components was disturbed, but viral RNA and protein synthesis remained unimpaired. By cell fractionation and Western blot analysis the amount of viral M protein located in the plasma membrane was found to be markedly reduced after treatment with C12, whereas in the cytoplasm the quantity of M protein was similar to that in untreated cells. C12 did not influence M protein synthesis, but prevented the binding of M protein to the host cell membrane, where the protein plays an essential role in virus assembly. Thus, treatment of VSV-infected cells with C12 resulted in inhibition of virus release. It is suggested that the newly synthesized triacylglycerols might interact with the host cell plasma membrane and interfere with virus maturation.
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Treatment of human carcinoma xenotransplants in athymic mice with recombinant human tumor necrosis factor (rh TNF) causes necrosis mainly in the central parts of the tumors, while peripheral sections remain mitotically active. As tumors are known to be supplied with adequate glucose exclusively in their periphery, the influence of the lack of glucose on the cytotoxic activity of rh TNF was studied. The absence of glucose enhanced the killing of tumor cell lines by rh TNF in tissue culture. Meth-A, a cell line known to be resistant to TNF in vitro but highly sensitive to it in vivo, was readily killed in tissue-culture medium lacking glucose. All non-transformed cell lines tested were found to be resistant to rh TNF, regardless of the presence or absence of glucose. In tumor-bearing mice a reduction of the blood glucose content augmented by insulin led to increased anti-tumor efficiency of rh TNF. The enhanced anti-tumor activity was reflected both in histological sections of the tumor xenotransplants, by extensive central necroses, and by reduction of the tumor volumes.
In the presence of undecanoic acid (C11) or lauric acid (C12) the synthesis of triacylglycerols was stimulated up to 10-fold both in tumor cell lines and in normal cell lines. Monocarboxylic acids of shorter or longer chain length either had no effect at all or were less effective. The increased triacylglycerol production was demonstrated, on the one hand, by the incorporation of radiolabeled glycerol into triacylglycerols and, on the other, by the incorporation of radiolabeled monocarboxylic acids, the incorporation of all (1-14C)-labeled monocarboxylic acids (C6, C12, C16, C18) regardless of their chain length, being preferentially enhanced by C11 and C12. C12 stimulated the de novo synthesis of triacylglycerols to such a degree that a 7-fold increase in the total amount of triacylglycerols per cell was observed during the first 10 hr of incubation. After removal of C12 from the tissue culture medium levels of triacylglycerols reach initial values again within 6 hr, indicating that the stimulatory effect of C12 is dependent on its continued presence. This led to the speculation that medium chain length monocarboxylic acids might be involved in the control of triacylglycerol synthesis.
Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation induces the dissociation of NF-kB from its inhibitor protein (IkB). The liberated NF-kB then binds to its proviral recognition sequence in the HIV-1 long terminal repeat (LTR) sequence. This step, however, is not sufficient to augment transcription. We demonstrate that NF-kB-mediated HIV-1 LTR activation is regulated by an additional event that is not dependent on IkB. A further phosphorylation event is proposed, since this step could be blocked by an inhibitor of a phospholipase C (PLC) type reaction. This inhibitor precludes the formation of diacylglycerols, which are required for activation of PKC isoenzymes. As an alternative pathway that is not dependent on PLC reactions, high-level transcription from the HIV-1 LTR is shown to require binding of both NF-kB and TAT.
In this retrospective study, the results of conservative treatment of 406 fractures of the distal radius are analysed and the limitations of conservative therapy indicated. In all, 107 male patients (average age 45 years) and 299 women (average age 65 years) were examined. In only one-third of these cases were both radiographically and clinically. Of the primarily dislocated fractures, 19% healed in the correct anatomical position with satisfactory to good clinical results. Up to now, treatment of fractures of the distal radius with dorsal tilting has been regarded as a form of conservative therapy. Although certain types of fracture, in particular unstable ones, have always been regarded as cases for operative treatment, no attempt has ever been made to define the limits between conservative and operative treatment. Evaluation of the results clearly indicates that the classification according to Frykman, the one most commonly in use, cannot be used as a primary criterion for operative treatment. In the course of a meticulous statistical evaluation, we defined the radiological parameters precisely with reference to shortening, dorsal tilt and instability and drew up a classification to define the primary indications for operation in cases of fracture of the distal radius. Shortening by over 3mm, dorsal tilting by over 10 degrees, presence of a dorsal debris zone, rupture, or osseous avulsion of the radioulnar syndesmosis as a further instability factor show the limits of conservative therapy and are clear indications for operative treatment.(ABSTRACT TRUNCATED AT 250 WORDS)