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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
PubMed1992

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↗
PubMed1991

[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↗
PubMed1990

[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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

[Treatment of open tibial fracture with fixateur externe].

External fixation with a Hoffmann or an ASIF frame was used in the treatment of 50 severe open lower leg fractures from 1979 to 1987. In 7 cases consolidation was achieved by means of external fixation without changing to any other method. Plaster cast fixation was subsequently performed after soft-tissue healing in 35 patients. Further methods of treatment applied after external fixation were intramedullary nailing in 5 cases, internal stabilization with a plate in 1 case and provision of a surgical support in 1 case. In 1 patient early amputation was necessary. On average, fracture healing took 6.7 (4-15) months, significantly correlating with the severity of soft-tissue lesion. Compound fractures of the proximal tibial shaft turned out to be problem cases, requiring up to 15 months for bone union. Acute infections occurred in 6 cases (12%), despite primary antibiotic prophylaxis. Nonunion was noted in 2 patients. A follow-up examination of 33 patients after a median of 45 months (range 6-99) showed full weight-bearing in all cases. Persistent soft-tissue problems were found in 7 patients, chronic osteitis in 4, and shortening of the extremity by up to 2 cm in 11 cases. One-third of the patients were out of work or had had to change their jobs as a social effect of their severe injuries.

Adolescent↗
PubMed1989

[Chronic fibular ligament insufficiency at the upper ankle joint. Late results after modified Watson-Jones plastic surgery].

The findings at clinical and roentgenological follow-up examination of 44 patients are reported to illustrate the long-term results of a modified Watson-Jones technique up to 90 months after the operation. The clinical results (86.3% of the patients without complaints and 88.6% with subjective stability of the ligaments) correspond with those given by a variety of sources in the literature. The roentgenological examination, on the other hand, showed signs of grade I or II arthrosis (Bargon scale) in 61.3% of cases, and arthrosis was worse than before the operation in nearly all cases. The patients in the group, that had received more conservative treatment with an average 6.3 years between lesion and surgical treatment (group 1), had the highest incidence of arthrosis, with 73.6%. In 10 cases the clinical examination revealed reduced supination and dorsiflexion attributable to the tenodesis effect associated with the Watson-Jones technique. In view of the high rate of arthrosis, younger patients and patients with a short tendon part of the peroneus brevis muscle should be treated by another, more "physiological" method.

Adolescent↗
PubMed1988

The extraction of high-molecular-mass DNA from hair shafts.

A simple and efficient method is presented for the extraction of DNA from hair shafts. DNA preparations obtained by this approach can be made amenable to restriction enzyme digestion, thereby allowing further molecular biological analysis.

Centrifugation↗
PubMed1988

Interruption of growth signal transduction by an antiviral and antitumoral xanthate compound.

The binding of growth factors to the cellular receptors elicits the phosphorylation of proteins which transmit growth signals to the nucleus [E. Rozengurt (1986) Science 234, 161-166]. Both the tyrosine-specific kinase (growth factor receptor) and the threonine-serine phosphorylating protein kinase C (pkC) become activated upon binding of the epidermal growth factor (EGF) to its receptor. Here we describe the selective inhibition of the pkC activation by tricyclodecane-9-yl-xanthogenate (D609) in the presence of unsuppressed receptor tyrosine autophosphorylation. As a consequence the affinity of EGF to the receptor was not down-regulated and the complex failed to be internalized.

Animals↗
PubMed1988

Inhibition of HIV-1 replication by an antiviral xanthate compound in vitro.

The antiviral xanthate compound tricyclodecan-9-yl-xanthogenate (code name D609) is capable of inhibiting DNA and RNA viruses in vitro. It can also inhibit the shedding of infectious HIV into the tissue culture medium from chronically infected lymphoma cells (KE37-III) as shown by infectivity assays and Western blots of the supernatant. HIV-specific proteins, however, were accumulated intracellularly. The initiation of a de novo HIV replication after infection of permissive KE37-1 cells was completely inhibited at concentrations of D609 which still permitted mitotic divisions of the cells. Furthermore, the selective antiviral activity of the xanthate compound was evidenced by the absence of HIV replicative intermediate DNA. The expression of cellular genes, such as c-myc, remained unimpaired within these cells.

Antiviral Agents↗
PubMed1988

Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract.

The DNA of distinct human papillomaviruses (HPVs) is regularly detected in the majority of human cervical carcinomas. In contrast to benign HPV-induced genital lesions, where the viral genomes are exclusively present as episomes, in cervical carcinomas HPV type 16 (HPV16) DNA was found to be integrated into the host DNA. In order to determine the physical state and expression of HPV DNA sequences at different stages of tumour development, we analysed a series of cervical lesions (mild, moderate and severe dysplasia and carcinoma in situ) that are considered precursors of carcinomas of the cervix. In 66.6% (18 of 27) of the tumours, HPV16 DNA was present. While in mild dysplasias only episomal HPV genomes were found, in all higher grade lesions integration of the viral DNA was detected. There was a close correlation between the episomal state and the expression of the HPV16 genomes: in 15 cases harbouring episomal HPV16 DNA (seven of which also contained integrated genomes) viral transcripts were present. We conclude that integration of HPV genomes takes place very early in cervical cancer development. In addition, the episomal state of the viral DNA depends on viral gene expression. The same conclusion, however, is not applicable in those lesions (three severe dysplasias) containing exclusively integrated HPV16 DNA. Thus, HPV16 DNA can persist in an integrated state without recognizable transcriptional activity. These results point to HPV16 as one potential prerequisite for the first steps in the multistage development of human cervical cancer.

Carcinoma in Situ↗