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Biomedical subjects

C Götz

Publications and source records attributed to C Götz.

33 records · Page 2Linked to original sources

Superoxide formation and macrophage resistance to nitric oxide-mediated apoptosis.

RAW 264.7 macrophages, when challenged with a combination of lipopolysaccharide (10 microg/ml) and interferon-gamma (100 units/ml), respond with endogenous NO. formation, which ultimately results in apoptotic cell death. Apoptosis is detected morphologically by chromatin condensation. Concomitantly we noticed the accumulation of the tumor suppressor protein p53. NO.-derived apoptosis was blocked by the NO.-synthase inhibitor NG-monomethyl-L-arginine. Repetitive treatment of RAW 264.7 macrophages with lipopolysaccharide/interferon-gamma, followed by subculturing viable cells, allowed us to select resistant macrophages which we called RES. RES cells still produced comparable amounts of nitrite/nitrate in response to agonist treatment but showed no apoptotic markers, i.e. chromatin condensation or p53 accumulation. However, RES macrophages undergo apoptosis in the presence of exogenously supplied NO., released from the NO-donors S-nitrosoglutathione or spermine-NO. Assessment of cytochrome c reduction established that RES cells released twice the amount of superoxide compared to RAW 264.7 macrophages under both resting and stimulated conditions. We linked increased superoxide production to cellular macrophage resistance by demonstrating decreased apoptosis after simultaneous application of S-nitrosoglutathione or spermine-NO and the redox cycler 2,3-dimethoxy-1,4-naphthoquinone. Our results suggest that macrophage resistance toward NO.-mediated apoptosis is, at least in part, due to increased superoxide formation. Therefore, the balance between reactive nitrogen and reactive oxygen species regulates RAW 264.7 macrophage apoptosis.

Animals↗

Valve repair for mitral regurgitation caused by isolated prolapse of the posterior leaflet.

BACKGROUND: Although prolapse of the posterior leaflet is the most common abnormality of the mitral valve causing dysfunction, the long-term results of mitral valve repair for this condition are seldom reported. METHODS: From October 1988 to June 1994, 208 patients (mean age, 59.4 years) with mitral regurgitation caused by isolated prolapse of the posterior leaflet underwent mitral valve repair alone or combined with myocardial revascularization (n = 30). The surgical techniques were quadrangular resection (n = 199) followed by annulus plication (n = 101) or sliding leaflet plasty (n = 98), use of artificial chordae (n = 5), or papillary muscle shortening (n = 4). All patients had an annuloplasty with a Carpentier ring. Mean follow-up was 3.4 +/- 0.1 years and total follow-up, 656 patient-years. RESULTS: There were six operative deaths (2.9%). Postoperative Doppler echocardiography found two cases of systolic anterior motion (1%), and echocardiographic studies at follow-up showed satisfactory mitral valve function in 97% of 112 patients. At 6 years, the actuarial survival rate was 87% +/- 7%, and freedom from thromboembolic complications, bleeding complications, and reoperation was 93% +/- 7%, 95% +/- 3%, and 95% +/- 4%, respectively. CONCLUSIONS: Mitral valve repair for regurgitation caused by prolapse of the posterior leaflet provides excellent survival at 6 years and should be considered the method of choice for its surgical treatment.

Adult↗

p21WAF1/CIP1 interacts with protein kinase CK2.

p21WAF1/CIP1 which belongs to a class of regulatory proteins that interact with cyclin dependent kinases is a potent inhibitor of these kinases. The inhibition of the cyclin dependent kinases induces an arrest of cells in the G phase of the cell cycle. In addition p21WAF1/CIP1 associates with PCNA and inhibits DNA replication. Here, we show that p21WAF1/CIP1 binds to the regulatory beta-subunit of protein kinase CK2 but not to the catalytic alpha-subunit. Binding of p21WAF1/CIP1 down regulates the kinase activity of CK2 with respect to the phosphorylation of the beta-subunit of CK2, casein and the C-terminus of p53. This study demonstrates a new binding partner for the regulatory beta-subunit of protein kinase CK2 which regulates the activity of the holoenzyme.

Amino Acid Sequence↗

A casein-kinase-2-related protein kinase is tightly associated with the large T antigen of simian virus 40.

The simian virus 40 (SV40) large T antigen is a multifunctional protein involved in SV40 cell transformation and lytic virus infection. Some of its activities are regulated by interaction with cellular proteins and/or by phosphorylation of T antigen by various protein kinases. In this study, we show that immuno-purified T antigen from SV40-transformed cells and from baculovirus-infected insect cells is tightly associated with a protein kinase that phosphorylates T antigen in vitro. In the presence of heparin or a peptide resembling a protein kinase CK2 recognition site, the phosphorylation of T antigen by the associated kinase is reduced whereas a p34cdc2-kinase-specific peptide has no influence. In addition, the T-antigen-associated protein kinase can use GTP and ATP as phosphate donors. These properties together with the observation that immunopurified T antigen can be phosphorylated by the addition of protein kinase CK2 suggest that at least one of the T-antigen-associated protein kinases is CK2 or a protein-kinase-CK2-related enzyme. The association of recombinant CK2 with T antigen was strongly confirmed by in vitro binding studies. Experiments with temperature-sensitive SV40-transformed cells provide evidence for a close correlation between cell transformation and phosphorylation of T antigen by the associated protein kinase.

Amino Acid Sequence↗

[Internal medicine complications of ventriculoatrial shunt].

BACKGROUND: Ventriculo-atrial shunts (VASs) and ventriculo-peritoneal shunts (VPSs) are the symptomatic treatment of choice for hydrocephalus. Bacterial contamination of the atrial part of VASs (usually with Staphylococcus epidermidis) can result in further organ complications, in most instances immune complex mediated glomerulonephritis ("shunt-nephritis") or direct microbial heart valve destruction. PATIENTS AND METHODS: In a retrospective study, we analyzed clinical and laboratory data of 11 patients with VAS associated complications as well as the course of the disease. RESULTS: The following complications were observed: glomerulonephritis (n = 9), glomerulonephritis and aortic valve destruction (n = 1), pulmonary embolism, pulmonary hypertension and tricuspid valve insufficiency (n = 1). Out of the 11 patients, 8 suffered from unexplained fever. All 11 patients had elevated circulating immune complexes. In 3 of 4 patients initially requiring dialysis, renal function improved which allowed to stop hemodialysis. Renal function also improved in 3 of 5 patients who presented with elevated serum creatinine. Unfortunately, the patient with multiple pulmonary embolisms and tricuspid valve insufficiency died of progressive pulmonary hypertension. CONCLUSION: The prognosis for impaired renal function is good only if the VAS infection is diagnosed early and an immediate surgical and antibiotic treatment leads to an eradication of the underlying chronic infection.

Adult↗

Kinetics of Photofrin II in perifocal brain edema.

Photodynamic therapy is under intense investigation as a possible adjuvant for the treatment of malignant tumors of the central nervous system. It relies on the fact that photosensitizers are selectively taken up or retained by malignant tissue. However, most brain tumors are accompanied by substantial vasogenic edema as a consequence of blood-brain barrier disruption within the tumor, leading to extravasation and propagation of plasma constituents into the surrounding brain tissue. Systemically administered photosensitizers may enter healthy tissue together with the edema fluid, possibly leading to sensitization of tissues outside the tumor. To test this hypothesis, vasogenic edema was induced by cold injury to the cortex in rats. The edema thus obtained is highly reproducible and very similar to tumor-associated edema. Just after injury induction, Photofrin II (PF-II), a commonly used photosensitizing agent, was administered at a dose of 5 mg per kilogram of body weight along with fluorescein isothiocyanate (FITC)-labeled albumin to mark edema advancement. After 1, 4, 12, or 24 hours, the brains were removed and frozen, and cryosections were studied with high-sensitivity video fluorescence microscopy for edema extravasation within the lesion and propagation of PF-II into the surrounding gray matter. PF-II advanced with edema along the corpus callosum underlying the cortex to a distance of 5 mm from the lesion after 4 hours. With the exception of the lesion, PF-II fluorescence returned to baseline after 24 hours, indicating subsequent washout. Propagation was comparable to the spreading of FITC-marked albumin. The authors conclude that photosensitizers spread with edema, an observation that may be pertinent to a number of questions concerning photodynamic therapy of cerebral tumors.

Animals↗

Synthesis of N-acetyl-9-O-acetylneuraminic acid alpha-p-amino-phenylthioketoside and its application as ligand in the affinity chromatography of a lectin with preferential affinity to O-acetylated sialic acids.

The N-acetyl-9-O-acetylneuraminic acid-alpha-p-aminophenylthioketoside 7 was synthesized as a sialidase-stable ligand for the affinity chromatography of a lectin with preferential affinity to O-acetylated sialic acids. The thioketoside was prepared by phase-transfer-catalysed glycosidation followed by Zemplen deacetylation. Regioselective acetylation of the completely de-O-acetylated derivative was practised by two different methods. The acetylation with trimethylorthoacetate did not show the desired selectivity for hydroxyl groups; in addition to the acetylation in position 9 extensive formation of an acetimidate ester derivative with the amino-group in the aminophenyl-moiety was observed. However the esterification with N,N-dimethylacetamide dimethyl acetal resulted in an exclusive acetylation of the hydroxyl-group in position 9. After catalytic hydrogenation this ligand was immobilized both directly and by a six-carbon long spacer group to the agarose matrix. The adsorbents were applied in the affinity chromatography of the lectin and their binding capacity and selectivity compared to those of the formerly used mucin matrix. In both respects the thioketoside coupled by the spacer turned out to be a better ligand for the isolation of the lectin than the mucin.

Acetylation↗

[Electronic data processing-assisted text processing at the clinic and in general practice].

Word processing is currently the most frequent application for personal computers, and a wide variety of standard software is available. The capabilities of modern word-processing software includes the convenient typing and correction of all routine correspondence, as well as the professional layout of scientific manuscripts. The decision to purchase a certain word-processing programm should be made according to local needs and prerequisities. Three to six months may be necessary to fully adapt the organization of a clinic or private practice to the new technology.

Computer Systems↗

[Potentiometric concentration determination of cyanide ions in waste water].

Electrodic systems, consist of gold or silver and metals of the IV, or V, subsidiary groups of the periodic system of elements are qualified for that, because they based strength of their electrodic steepness, selectivity, potentionel stability and sensibility by destination of cyanid ions in waste-water. We are going to introduce a fast-analysis-method for cyanid ions in waste-water of technical processes, which had been tested practically by the continuous control of limits, demanded by the legislator.

Calibration↗

[Diagnosis of myocardial ischemias with long-term electrocardiography: spontaneous variability and modification by nitrate therapy].

To evaluate spontaneous variability of ST-segment changes within the Holter ECG, in 20 patients with documented coronary heart disease (CHD) long-term ambulatory ECG recordings were performed over 3 consecutive days, when the patients were only receiving short-acting nitrates. ST-segment alterations per day were measured as the area beneath the baseline (mV x min), and were compared day-to-day intraindividually. The intra-day variations of ST-segment area alterations were a factor of about 10, when compared with the baseline values. Following administrations of 120 mg ISDN ret. at the beginning of day 4, the number of anginal attacks was reduced, as was the acute medication with short-acting nitrates. There was also a trend to reduction of ischemic ST-segment changes, but these reductions could not be confirmed statistically. In studies on the course and therapeutic interventions of patients with CHD, the phenomenon of spontaneous variability of ST-segment alterations must be taken into account--as applies also to the arrhythmia analysis within the Holter ECG--and the recording period must probably be prolonged beyond the 24-h limit presently used.

Adult↗

[Use of electronic data processing in the urologic clinic and practice--possibilities and perspectives].

The development, present status and future trends in the use of computers in urology in the Federal Republic of Germany are reviewed. The hardware, software required for hospital and private practice and the staff needed are discussed. Proposals are given for the installation and stepwise upgrading of computer systems, from simple text processing units to complex hospital communication systems. Finally new technologies that might considerably change the use of computers in urology are presented.

Computers↗