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Biomedical subjects

G Sauer

Publications and source records attributed to G Sauer.

At least 37 records · Page 2Linked to original sources

[First annual report of practitioners of interventional cardiology in private practice in Germany. Results of procedures of left heart catheterization and coronary interventions in the year 1996].

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.

Angiocardiography↗

Oral manifestations of HIV infection in 600 South African patients.

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.

AIDS-Related Opportunistic Infections↗

Development of activity patterns in auditory nerve fibres of pigeons.

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.

Aging↗

TNF accelerates the S-phase of the cell cycle in tumor cells.

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.

Animals↗

Lauric acid inhibits the maturation of vesicular stomatitis virus.

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.

Animals↗

Glucose depletion enhances the anti-tumor effect of TNF.

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.

Animals↗

Medium chain length fatty acids stimulate triacylglycerol synthesis in tissue culture cells.

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.

Cell Line↗

Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.

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.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Indications for surgery in distal radius fractures].

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)

Adolescent↗

[Coronary angioplasty with the implantation of a vascular support (stent)].

Coronary angiography in a 55-year-old man with coronary heart disease and typical physical activity-induced angina revealed a subtotal stenosis in the middle third of the right coronary artery while left ventricular function was normal. Percutaneous transluminal coronary angioplasty (PTCA) was performed in January 1989, achieving a residual stenosis of less than 50%. However, restenosis of more than 90% developed within six months, necessitating another PTCA, followed immediately by implantation of a metal (Palmaz-Schatz) stent in the stenotic area. No stenosis was demonstrable afterwards. Maintenance medication with anticoagulants (phenprocoumon) and platelet-function inhibitors (aspirin and dipyridamole) was instituted and repeat angiography three months later demonstrated good dilatation results without any restenosis.

Angioplasty, Balloon, Coronary↗

Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan-9-yl-xanthogenate and lauric acid.

Recombinant human tumor necrosis factor (rh TNF) when administered intravenously together with the phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate (D609) and lauric acid (C12), leads to the partial regression of various human tumor transplants in athymic mice. Extensive necrosis occurred after a single intravenous infusion, with no detectable side effects. TNF-mediated cytotoxicity was found to be correlated with the depletion of energy in HeLa cells. The activity of rh TNF was enhanced by the absence of glucose, while it was reduced by addition of extraneous ATP. In the presence of rh TNF, D609, and C12, cellular energy metabolism was almost completely switched to glycolysis. Under these conditions the cytocidal activity of rh TNF on HeLa cells was amplified at least 60-fold.

Animals↗

Restoration of the responsiveness to growth factors in senescent cells by an embryonic cell extract.

In senescent fibroblast cell cultures which have approached a postmitotic stage in vitro, responsiveness to growth factors is restored upon exposure to an embryonic sheep cell extract. The extract contains molecules below a molecular weight of 1 x 10(5) Da in aqueous solution. Following a transient exposure to the extract, mitotic activity is resumed, and the cells keep dividing over several passages. The target cells which respond to the treatment were identified in a single-cell assay as those that still had the capacity to undergo at least several mitotic divisions before entering the final stage of senescence.

Animals↗

Antitumoral activity of a xanthate compound. I. Cytotoxicity studies with neoplastic cell lines in vitro.

Xanthate derivatives were shown previously to display antitumor activity against transformed fibroblasts and lymphoma cells in combination with monocarboxylic acids [1]. Various malignant cell lines of human origin were treated in vitro to explore the range of antitumoral activity of the compounds. The combination of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic acid (C11) exerted dose dependent cytotoxic and antiproliferative effects on cell lines both from solid tumors (glioblastomas, colon-carcinomas) and hematological diseases (lymphomas, CML/BC). Additionally, the combination of D 609/C11 was able to kill both methotrexate- and adriamycin-resistant L 1210 and S 180 cells, indicating that there is no cross-resistance for these drugs and D 609/C11 in vitro.

Antineoplastic Combined Chemotherapy Protocols↗

Antitumoral activity of a xanthate compound. II. Therapeutic studies in murine leukemia and tumor models in vivo.

The combinations of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic acid (C11) and D 609 with myristic acid (C14) were tested in 3 rodent tumor models in vivo. D 609 in combination with C11 or C14 did not show antitumoral efficacy in 3-Lewis lung carcinoma (3-LL) growing in syngeneic C57BL6-mice (primary tumor and metastasis) or in WEHI-3B myelomonocytic leukemia growing in Balb/c mice, when given in a dose range lower than the lethal dose for 10% of the treated animals (LD10). In L 1210 mouse lymphoid leukemia growing in CD2F1 mice the combination of D 609/C11 given intraperitoneally in a concentration of 100 mg/kg for more than 1 day effected a significant difference in the survival curves between the control and therapeutic groups in 1 out of 2 experiments. In conclusion, the treatment schedules of D 609/C11 or D 609/C14 used in this study has not revealed significant therapeutic effects in mouse tumors or leukemias in vivo.

Animals↗

Mechanistic aspects of the synergistic antiviral effect of xanthates and monocarbonic acids.

The xanthate tricyclodecan-9-yl-xanthogenate (D609) displays antiviral and antitumoral properties that are inversely proportional in vitro to the serum concentration. Accordingly, it has been found that D609 binds to serum albumin. Recently, we have reported that D609, in combination with undecanoic acid, has a synergistic antiviral effect, which appears, as shown here, to be due to competition for the same binding domain on serum albumin. Furthermore, undecanoic acid fosters the binding of D609 to the cell. Both the competition of D609 with monocarbonic acid for binding on serum albumin and the enhanced binding of xanthate to the cell are dependent, in accordance with previously reported results, on the chain length of the fatty acids. Eleven to 14 C-atoms (undecanoic, lauric and myristic acid) were found to be appropriate while shorter (C6) and larger (C18) monocarbonic acids were shown to lack synergistic properties.

Binding, Competitive↗

Tumor prevention by a xanthate compound in experimental mouse-skin tumorigenesis.

The antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609), which is an inhibitor of protein kinase C activation, has been used for tumor prevention in vivo. When applied chronically together with 12-O-tetradecanoylphorbol-13-acetate (TPA) in the classic initiation-promotion mouse-skin model, D609 prevented tumor induction in a dose-dependent manner. At the concentration that inhibited tumor formation by 97%, no toxic effects were detected and the TPA-induced hyperplasia remained unaffected. As D609 failed to prevent the activity of a chronically applied carcinogen, it is concluded that the observed tumor prevention achieved with D609 is tumor-promotion-specific and is not due to killing of tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗