Biomedical subjects
Publications and source records attributed to T Wagner.
A case of a neoplasm called non-osteogenic fibroma or non-ossifying fibroma is reported. The neoplasm was situated in the cervical part of the spine and was removed surgically. A peculiarity of this case is rare occurrence of this neoplasm and oligosymptomatic stationary course of the disease.
In 10 female patients with carcinoma the effect of a single dose of 5-fluorouracil on morphologic alterations of the small bowel mucosa, intestinal disaccharidase-activities and lactose-tolerance-test was studied pre- and 96 hours posttherapy. After having given a standard dose of 1,25-1,50 gr 5-fluorouracil intravenously ( = 22 mg per kilo body weight) histologic changes of the small bowel mucosa (slight edema and shortening of the villi) were noted only in 4 cases. In the other cases the small intestine showed no morphological alterations of the mucosa. In all patients the lactose-tolerance-test after therapy with 5-fluorouracil was not affected. Following the administration of 5-fluorouracil no reduction of intestinal disaccharidase activities (maltase, saccharase, lactase) was observed. As a consequence of our results we suppose, that a patient given a single dose of 5-fluorouracil intravenously needs no specific diet without milk or milk-products.
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The hydroperoxy and several alkylthio derivatives of the antitumor agents cyclophosphamide (2-bis(2-chloroethyl)amino tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide), ifosfamide (3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-2H-1,3,1-oxazaphosphorine 2-oxide) and trofosfamide (3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) were characterized by electron impact and field desorption mass spectrometry. The compounds, which are stabilized derivatives of the activated hydroxylated intermediates of cyclophosphamide (ifosfamide, trofosfamide), could be identified as 4-hydroperoxy and 4-alkylthio oxazaphosphorines. The existence of diastereomers of these products was demonstrated by thin-layer chromatography and f.d. mass spectra. Derivatization with benzylmercaptan was found to be an appropriate method for the quantitative isolation and mass spectral identification of the activated metabolic intermediates of cyclophosphamide from biological material. Using this reaction, 4-hydroxycyclophosphamide and its acyclic tautomer, aldophosphamide, which are too unstable for direct identification, were detected in urine and serum of patients treated with 3H-cyclophosphamide.
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An assay for the characterization and quantitative determination of activated cyclophosphamide has been described. The method is based on high reactivity of the kryptaldehyde group in 4-hydroxycyclophosphamide with mercapto compounds to yield 4-(S-R)mercaptocyclophosphamide derivatives. The activated cyclophosphamide can be converted quantitatively to 4-(S-benzyl)mercaptocyclophosphamide with benzyl mercaptan, and the mercapto derivative can be separated by thin-layer chromatography on silica gel with ethyl acetate:methyl ethyl ketone as solvent. Using this assay, significant levels of activated cyclophosphamide in the blood of mice and rats, as well as of humans, were found to be present after cyclophosphamide application. The characterization of 4-(S-benzyl)mercaptocyclophosphamide formed was confirmed by comparing the thin-layer chromatographic and mass spectrometric data on this derivative obtained from an authentic sample of 4-hydroxycyclophosphamide.
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Studies on the enzymatic inhibition of phenylalanyl-tRNAPhe and formylmethionyl-tRNAFMet binding to the ribosomes by defined tRNA fragments indicate that beside the anticodon the following regions of tRNA are important for ribosomal A-site interaction: the TppsipCp sequence, the CpCpA end, and hU loop. In contrast, binding to the ribosomal P site is not inhibited by the fragments of uncharged yeast tRNAPhe containing the hU or the TpsiC loop of the molecule. Comparative studies on the inhibitory effect of the oligonucleotides TppsipCpGp and UpUpCpGp indicate that the presence of the minor bases in TpsiC loop is not an essential prerequisite for the binding of tRNA to the ribosomal A site. Furthermore, evidence is presented that shows that the binding of the TppsipCpGp oligonucleotide to the ribosomes influences the ribosomal P site and increases there the efficiency of the codon-anticodon interaction. It is suggested that the TppsipCpGp binds to the ribosomal A site and competes there with the TpsiC loop of the aminoacyl-tRNA for the same binding site. A model for the interaction between tRNA and the ribosomal A site is proposed that involves partial unfolding of hU and TpsiC loops of the tRNA and, therefore, suggests the dynamic involvement of tRNA in protein synthesis.
Four cases of arteriosclerotic aneurysm of the arteria lusoria are described. In one patient a tumor of the superior mediastinum was suspected, the chief signs of which are dyspnea and irritative cough. In a further patient, enlargement of the left superior mediastinum was noted in routine fluoroscopy. Clinical investigation revealed an aneurysm of the arteria lusoria. In the third patient, dysphagia, slight cough and torticollis were interpreted as symptoms of a neoplasm of the esophagus or larynx. The fourth patient, in whom aneurysm of the arteria lusoria was discovered by chance at autopsy, displayed no clinical or radiological signs. Abberrant right subclavian artery (arteria lusoria) is a relatively frequent finding in autopsies. Aneurysm of the arteria lusori is apparently also a typical complication.
The existence of the cyclophosphamide (CP) metabolites, 4-hydroxycyclophosphamide and aldophosphamide, in vivo after application of CP to mice and rats has been demonstrated. The metabolite pattern in the serum and urine of rats at different times after CP application was determined. For this purpose, thin-layer chromatograpic procedure was developed which allows separation of the metabolites without decomposition. Because considerable amounts of radioactivity are bound to serum proteins after 3H-CP application, protein binding studies with CP and CP metabolites were carried out. It was found that 4-hydroxycyclophosphamide is bound to thiol groups of bovine serum albumin yielding a rather stable product which could be isolated by column chromatography on Sephadex.
4-Hydroperoxycyclophosphamide was obtained in approximately 20% yield by ozonization of cyclophosphamide in acetone/water at 0 degrees C. It was reduced to 4-hydroxycyclophosphamide, which was treated with several mercaptans to yield compounds of the type 4-(S-R)-mercapto-cyclophosphamide. In the solid state these compounds are stable at room temperature; in aqueous solution they are hydrolyzed to 4-hydroxycyclophosphamide or its tautomer, aldophosphamide. One of the 4-(S-R)-mercapto-cyclophosphamide compounds was tested biologically in vitro against Yoshida ascites tumor cells and showed the same cytotoxic activity as 4-hydroxycyclophosphamide.
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