Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein.

Prion diseases are fatal neurodegenerative disorders in man and animal associated with conformational conversion of a cellular prion protein (PrPc) into the pathologic isoform (PrPSc). The function of PrPcand the tertiary structure of PrPScare unclear. Various data indicate which parts of PrP might control the species barrier in prion diseases and the binding of putative factors to PrP. To elucidate these features, we analyzed the evolutionary conservation of the prion protein. Here, we add the primary PrP structures of 20 ungulates, three rodents, three carnivores, one maritime mammal, and nine birds. Within mammals and birds we found a high level of amino acid sequence identity, whereas between birds and mammals the overall homology was low. Various structural elements were conserved between mammals and birds. Using the CONRAD space-scale alignment, which predicts conserved and variable blocks, we observed similar patterns in avian and mammalian PrPs, although 130 million years of separate evolution lie in between. Our data support the suggestion that the repeat elements might have expanded differently within the various classes of vertebrates. Of note is the N-terminal part of PrP (amino acid residues 23-90), which harbors insertions and deletions, whereas in the C-terminal portion (91-231) mainly point mutations are found. Strikingly, we found a high level of conservation of sequences that are not part of the structured segment 121-231 of PrPcand of the structural elements therein, e.g. the N-terminal region from amino acid residue 23-90 and the regions located upstream of alpha-helices 1 and 3.

Intra-arterial chemotherapy of the liver with transient, repeated hypoxia.

Intra-arterial liver perfusion with transient repeated hypoxia via an indwelling double-lumen polyurethane catheter was undertaken in 25 of 33 patients with diffuse metastases involving 50%-70% of the liver, and whose primary cancer had previously been treated by local radical resections. Treatment continued over 3-12 months until disease progression and over 3-24 months until thrombosis. In 24 patients with colorectal carcinoma the 1-year survival rate (using the actuarial method) was 79% +/- 17%. The treatment morbidity was low. It is concluded that this form of treatment improves the quality of life and gives safe and effective palliation to the patients.

[Superselective arterial tumor angiography and chemotherapy. Preliminary results (author's transl)]. / Superselektive arterielle Tumorangiographie und Chemotherapie - Bericht über unsere ersten Erfahrungen.

In 7 patients with bone and soft tissue sarcoma super-selective angiography with chemotherapy was performed. Both showed a low rate of complications. In 2 patients we saw a total and in 3 a subtotal tumor-regression. A residual tumor was eliminated after systemic chemotherapy. Beside the tumor vessels treated in the first session, we found other initially unimportant ones. These showed increased size during subsequent angiography and allowed further injection of chemotherapeutic agent into the residues of the tumor. We found that each part of the tumor has its own separate blood supply.

[Treatment of inoperable liver metastases: preliminary results with intrahepatic chemotherapy via a new type of indwelling catheter (author's transl)]. / Therapie inoperabler Lebermetastasen. Erste Erfahrungen mit der intrahepatischen Chemotherapie unter Verwendung eines neuen Verweilkatheters.

Intra-arterial liver perfusion of cytostatic drugs via an indwelling double-lumen polyurethane catheter was undertaken in 17 patients with diffuse metastases involving 50-70% of the liver and previously treated by radical local resections. Treatment continued over 3-20 months (mean 8.4 months). In ten patients with colorectal carcinoma treatment lasted for 7 months, follow-up for a mean of 14 months (range 5-24 months), and the one-year survival time (using the actuarial method) was 79 +/- 26%. The toxicity was well controllable. It is concluded that this form of treatment improves quality of life in such patients.

Chromosome studies on lymphocytes of patients under cytostatic therapy. II. Studies Using the BUDR-labelling technique in cytostatic interval therapy.

Lymphocyte cultures from the peripheral blood of 38 patients undergoing a cytostatic interval therapy with a regimen of methyl-CCNU (1-[2-chloroethyl-3-(4-methyl-cyclohexyl)]-1-nitrosourea), 5-fluorouracil, and vincristine (each 5-day course of therapy was followed by a therapy interval of 4 weeks) were supplied with 5-bromodeoxyuridine (BUDR) for the whole culture time to determine the sister chromatid labelling pattern. From a total of 92 individual blood samples sister chromatid exchange (SCE) studies were performed including analyses before the start of the therapy, and immediately and 4 weeks after each course of therapy. In addition, the frequency of first, second, and third metaphases in the 72-h cultures was estimated using the characteristic labelling patterns. A distinct increase of SCE frequency over the control level (i.e., lymphocyte cultures of patients before the start of therapy) was observed at all phases of therapy. It was clearly correlated with the number of courses of therapy up to course 7, later on the SCE rate remained more or less at the level reached. The influence of the composition of each drug regimen on the SCE rate was less pronounced than it was on the breakage rate. Moreover, although a clear correlation existed between the individual rates of breakage and SCE, the formation of the latter appeared to reflect a long-term effect of the therapy rather than did the formation of break aberrations. In addition, as the intercellular variability of the number of SCEs per cell was much higher than that of breaks, the interindividual variability (variation of the mean values for each patient) was small compared to the respective variability of breakage rates. The proportion of first, second, and third metaphases present in 72-h cultures evidently was influenced by single courses of therapy. The observed delay of proliferation was also reflected in different amounts of chromosome damage. Although the BUDR treatment enhanced the cytostatic effect of the therapy on the lymphocytes in culture rendering SCE analysis rather difficult in several cases, the other data of this study and in particular the experiences with the "long-term effect" make it imperative to include BUDR-labelling in further cytogenetic studies in subjects with exceptional exposure to chemicals. However, the SCE method can by no means, replace the classic cytogenetic analysis.

[Fibrin glue. A new treatment technic in persistent recurrent spontaneous pneumothorax]. / Fibrinklebung. Eine neue Behandlungsmethode beim persistierenden und rezidivierenden Spontanpneumothorax.

The treatment of choice in idiopathic spontaneous pneumothorax is continuous suction drainage by chest tube for 8--10 days. If this method is not successful, i.e., in patients with a persistent or recurrent pneumothorax, an attempt can be made to produce local pleural adhesions by means of a special fibrin glue, especially in patients with poor general condition. This fibrin glue pleurodesis was performed successfully in seven patients, four of them having a persistent, two a recurrent, and one an iatrogenic pneumothorax. Six of them are now, 3--10 months after therapy, without a recurrence and free of discomfort. One patient died 6 days after treatment from a cerebral stroke. Autopsy showed fibrinous adhesions in the area of the upper lobe. Good tissue compatibility was confirmed histologically.

[Sonographic thyroid diagnosis]. / Sonographische Schilddrüsen-Diagnostik

Sonography is suitable for the examination of thyroid glands respectively goiters. This method particularly gains in the differentiation of cold nodules or cold regions. In more than 50% of patients with cold nodules sonography showed cystic lesions. In addition, ultrasonically guided percutaneous fine needle biopsy is employed for emptying cysts or gaining material for cytological examination.

[Glucose, fructose and xylitol as energy carriers in postoperative parenteral nutrition (comparative studies) (author's transl)]. / Glucose, fructose und xylit als Energieträger in der postoperativen parenteralen Ernährung. Vergleichende Untersuchungen

The effects of fructose, glucose and xylitol, as well as their mixture in a proportion of 2:1:1 were measured and compared in the postoperative phase in a uniform group of patients receiving these substances during a 6-hour infusion. Carbohydrate balance, carbohydrate blood levels, changes in acid-base equilibrium and rises of lactate and uric acid were used as criteria for assessing the various substrates and their mixtures. Using these criteria, a carbohydrate mixture consisting of fructose, glucose and xylitol (2: 1: 1) proved to be better than the various substrates by themselves in equivalent amounts.