[Cytochrome P-450-catalyzed xenobiotic metabolism--initial results with an in vitro test system].
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Biomedical subjects
Publications and source records attributed to G Wagner.
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A new edition of the TNM classification of malignant tumours will be published in spring 1987 by UICC. This 4th edition is an internationally uniform and updated classification of tumours by their anatomical extent and is indispensable for treatment planning and evaluation of treatment results in cancer patients.
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The separation of FIGO stage I b cervical carcinoma into a new histological stage I b1 and a stage I c (deep infiltration confined to the cervix) leads to an essential difference in therapeutic results. 5-year survival of 152 cases consigned to the new stage I b1 was 92%, whereas that of 95 cases of the new stage I c was only 77%. Hence, 5-year survival of stage I c patients is lower than of FIGO stage II a (83%). Contrary to our earlier practice, since 1976 all stage I c cases have received postoperative irradiation (Cobalt60). 5-year survival of 75 stage I c cases without lymph node metastasis was 83% when treated by surgery alone; 5-year survival of 22 similar cases treated by surgery and postoperative irradiation was 82%. There is no benefit of postoperative irradiation in cases of stage I c cervical carcinoma when the lymph nodes are not affected.
A total of 54 of the 58 alpha-carbon resonances and numerous side-chain carbon signals were individually assigned in the basic pancreatic trypsin inhibitor by using two-dimensional heteronuclear correlated and relayed coherence transfer spectroscopy with proton detection. No isotope enrichment was used, and the spectra were recorded in 5-mm sample tubes. The pulse sequences were optimized to eliminate, prior to phase cycling, the signals of protons attached to 12C. We have concentrated on assignments of carbons bearing a single hydrogen in view of a relatively easy interpretation of carbon relaxation times, and most of these carbon resonances could be assigned. Furthermore, we demonstrate that two-dimensional heteronuclear correlated and relayed coherence transfer spectra can be used to elucidate connectivities between degenerate resonances within proton spin systems that often occur in threonines and aromatic side chains.
The complete sequence-specific assignment of the 1H nuclear magnetic resonance spectrum of a major subform of rabbit liver metallothionein-2 is presented. The sequential assignment procedures revealed a number of differences with regard to results obtained by earlier partial chemical sequencing of a preparation now known to be microheterogeneous. In particular, the present data indicate a polypeptide chain length of 62 amino acid residues as compared to the occurrence of 61 amino acids in all other known mammalian metallothioneins. In the new sequence, which was also fully confirmed by chemical means, the additional amino acid residue was identified as Ala8' inserted between Ala8 and Ala9 of the standard amino acid numeration. In addition to the predominant protein species all preparations contained a minor component, for which the two-dimensional 1H-nuclear magnetic resonance features are compatible with a chemically different, homologous metallothionein.
The solution conformation of rabbit liver Cd27+-metallothionein-2 was determined by nuclear magnetic resonance (n.m.r.) and distance geometry. The n.m.r. data are based on complete sequence-specific resonance assignments for the polypeptide chain. This letter describes the global arrangement of the polypeptide chain, which forms two distinct domains containing metal clusters of three and four Cd ions, respectively.
Analysis of 1H-1H nuclear Overhauser effects and amide proton-C alpha proton coupling constants in rabbit liver metallothionein-2 resulted in the identification of two segments of 3(10)-helix and numerous secondary structure elements of a novel type, which we call "half-turn". A half-turn can be generated starting from a type II tight turn by rotation of phi 3 from +90 degrees to -90 degrees. Its appearance in metallothionein appears to be a consequence of the constraints on the polypeptide conformation by the large number of metal binding sites.
A total of 2994 cases of previously untreated colorectal carcinomas taken from the database of the International Cancer Patient Data Exchange System of the UICC were analyzed. The objective was to compare pretherapeutic and postsurgical data and to investigate the impact of missing information on the quality of tumor staging under routine conditions. In clinical staging, a higher percentage of items were marked "unknown" in the questionnaires than in histopathological staging. The clinical and postoperative assessment of TNM stages Ib, II, and III frequently diverged, indicating a low precision for clinical staging. Fistulae were rarely observed in either colon or rectum carcinoma.
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Between 1970 and 1979 202 women of 40 years of age or younger were treated for invasive cervical cancer at the 1st Department of Obstetrics and Gynaecology of the University of Vienna. 77 patients received primary irradiation therapy (radium and cobalt-60), 125 underwent surgery. These cases were compared with 1586 patients of all ages who received primary radiation therapy. Of the women under 40 receiving only radiation therapy, the survivors were divided into the following categories: stage I:84.6% of 13 cases stage II:69.2% of 13 cases stage III:35.1% of 37 cases stage IV: 0% of 14 cases. The survival rate for all age groups receiving primary radiation therapy was: stage I:76.0% of 225 cases stage II:52.9% of 429 cases stage III:42.9% of 801 cases stage IV:11.4% of 131 cases. There was no significant difference in the 5-year survival rate between the older and younger women. However, a more promising trend for the younger women receiving primary radiation therapy may be expected. The younger women were observed to have irreversible complications (fistulas) at a rate of 7.7%, whereas the rate of comparable patients receiving radiation therapy was 0.6%. The younger women having stage III and IV cancer were found to develop fistulas at a rate of 17.6%, while both groups together had a rate of only 3.2%. Hence, primary radiation therapy for younger women must be considered as involving a relatively high rate of complications. For younger women with stage I cancer the survival rate after radical surgery was 88.8% (98 cases), after radiation therapy 84.6.(ABSTRACT TRUNCATED AT 250 WORDS)
In hypokalaemia the incidence of cardiac toxicity with digitalis is increased, possibly through changes in the affinity or capacity of the digitalis receptor in the heart. Previous studies have reported an increased ouabain binding capacity or Na+-K+ ATPase activity after hypokalaemia in human erythrocytes and rabbit and guinea pig hearts and no change or decreases in rabbit or rat skeletal muscles with no changes in ouabain affinity. The present study determined (a) the effect of potassium on 3H-ouabain binding to normokalaemic guinea pig cardiac cell membranes, (b) the effect of acute hypokalaemia induced by a potassium deficient diet for 14-18 days in guinea pigs on 3H-ouabain binding to erythrocytes and cardiac and skeletal muscle homogenates, and (c) ouabain induced inotropy in isolated contracting guinea pig left atria, right ventricular papillary muscles, and soleus muscle strips from normokalaemic and hypokalaemic guinea pigs. 3H-ouabain binds to cardiac cell membranes in the presence of magnesium and inorganic phosphate with an affinity (KD value) of 1.13 X 10(-7) mol X litre-1. Potassium decreased this affinity without changing the binding capacity. Erythrocytes and heart muscle homogenates showed the same affinity as cardiac cell membranes, whereas soleus muscle homogenates had a higher affinity for ouabain (KD 5.1 X 10(-8) mol X litre-1). After hypokalaemia, the ouabain affinity did not change in any tissue.(ABSTRACT TRUNCATED AT 250 WORDS)