Development of cytochrome P-450-altered preneoplastic and neoplastic lesions during nitrosamine-induced hepatocarcinogenesis in the rat

The expression of four cytochrome (cyt.) P-450 isoenzymes has been studied in preneoplastic and neoplastic lesions during the course of nitrosamine-induced hepatocarcinogenesis in the female Wistar rat. Following exposure to diethylnitrosamine (50 or 100 ppm in the drinking water) for 10 days, animals were taken sequentially, and the livers were analyzed for the evolution of adenosine triphosphatase deficient focal lesions. These lesions were subdivided into different phenotypes with regard to their cyt. P-450 isoenzyme expression using serial frozen sections. Our results demonstrate that about 40% of the adenosine triphosphatase-deficient lesions show concomitant alterations in their cyt. P-450 isoenzyme contents. Of these lesions, islets which are characterized by decreased levels of at least three cyt. P-450 isoenzymes show a dramatic increase in their volumetric fraction of liver tissue with progression of time. Although only very few lesions express this phenotype, the contribution to the volumetric fraction of islet tissue raises from about 2% at 10 weeks to about 60% at 35 weeks after cessation of diethylnitrosamine treatment. By contrast, lesions which express less than two alterations in cyt. P-450 isoenzyme levels develop relatively slowly. Similar results were obtained when animals were exposed continuously to diethylnitrosamine for a period of up to 8 weeks. Following treatment of islet-bearing animals with phenobarbital, an induction of cyt. P-450 isoenzymes and NADPH-cyt. P-450-reductase was observed within preneoplastic and neoplastic lesions. This induction was most pronounced in large, expansively growing nodules, a type of lesion which displayed decreased levels of these enzymes in livers of animals not treated with phenobarbital. The elevation of the cyt. P-450 isoenzymes disappeared within 2 to 3 weeks after cessation of inducer treatment. Our results indicate that a high proportion of rapidly growing lesions has assumed a constitutive deficiency in cyt. P-450 isoenzyme expression during nitrosamine-induced hepatocarcinogenesis. This deficiency, however, is not an irreversible quality, since individual cyt. P-450 isoenzymes can be markedly induced by treatment with an enzyme inducer like phenobarbital. Thus, the observed decrease in cyt. P-450 expression during development of malignancy does not result from alterations in the cyt. P-450 encoding structural genes but may rather be related to abnormalities in the function of regulatory systems of a higher order which may play a central role in the maintenance of cell homeostasis.     

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Postoperative evisceration

From 1930 to 1989 postoperative rupture of abdominal wound occurred in 0.42 per cent (n = 82) in the Department of Obstetrics and Gynaecology of the University of Rostock. 60 per cent of the patients were younger than 50 years. Patients of reduced general condition and anaemia were predisposed to this complication. We observed postoperative alterations of the respiratory tract in 13 per cent and alterations of the gastro-intestinal tract in 20 per cent which lead to increased intra-abdominal pressure. We observed postoperative wound rupture only in 8 cases after Pfannenstiel's incision, but all other times after median section, predominantly during the 7th and 12th postoperative day. All patients were treated by secondary suture, immediately. 8 patients came to death, three of them had no direct link to wound rupture. For prophylaxis the use of non-absorbable suture material, safety sutures, intraoperative blood and protein substitution and prevention of affections of the respiratory system and gastrointestinal tract are recommended.     

Effect of bite tray impression technique on relocation accuracy in frameless stereotactic radiotherapy.

A previously developed method for achieving patient relocation in fractionated stereotactic radiotherapy (attachment of an infrared fiducial system to a bite tray) relies on the integrity of a bite tray system that incorporates moulding to the patient's upper dentition. Reproducible and accurate patient positioning requires stability of the bite tray and mould during the full treatment process, both during the time the bite tray is inserted in the patient's mouth, and between separate bite tray insertions. The optimum construction method for a stable reproducible tray has not been sufficiently investigated. We undertook a study to identify factors which might influence the integrity of the hard palate bite tray system. Reprosil Fast Set Putty was used to construct 3 impression conditions; teeth only; teeth and alveolar sulcus; and teeth, alveolar sulcus, and the hard palate. Reproducibility was assessed by volunteers inserting the impressions multiple times and recording the locations of 8 standard reference points. Our results showed the optimal impression technique (i.e., the one that led to the smallest ranges in positional and rotational errors) was that which incorporated the teeth, alveolar sulcus, and hard palate.     

Identifying the affected hemisphere by 1H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.     

Twelve of fourteen surface epitopes of receptor-bound human chorionic gonadotropin (hCG) being antibody-inaccessible suggest an extensive involvement of the long extracellular domain of the hCG receptor.

On the surface of the free (receptor-unbound) form of hCG, we have previously identified 14 topographically distinct epitopes (Schwarz et al. (1986) Endocrinology 118, 189-197; Berger et al. (1990) J. Endocrinol. 125, 301-309). Here we report that only two of them, i.e. the (adjacent) beta 3 and beta 5 epitopes, can be recognized by 125iodine-labeled monoclonal antibodies when hCG was specifically bound to the rat testis hCG receptor. The exclusive accessibility of precisely these two surface epitopes indicates that hCG assumes a defined rather than a stochastic orientation in its receptor-bound state. The inaccessibility of 12 of 14 epitopes is consistent with the idea that the 341 residues long extracellular domain of the recently cloned hCG receptor (MacFarland et al. (1989) Science 245, 494-499) is the ligand binding domain. It is proposed that the extracellular domain is folded in a way that a cavity is formed large enough to accommodate hCG. Thereby, a considerable portion of the total surface of hCG is covered, as reflected by the masking of most of its epitopes.     

Radiologische und histologische Beobachtungen an zentralen Talusfrakturen

In einer prospektiven Studie zentraler Talusfrakturen wurden radiologische Daten (Nativr?ntgenbild, CT, MRT) auf ihre Korrelation zum histologischen Befund (Biopsie zum Zeitpunkt der Schraubenentfernung) überprüft. Bei 9 Frakturen an 8 Patienten (Alter 14 – 48 Jahre) handelte es sich um Frakturen des Typs Hawkins I und II je einmal sowie des Typs III viermal; in 3 weiteren F?llen lagen K?rperfrakturen vor. Innerhalb von 24 h nach dem Unfall wurden 7 Frakturen verschraubt und 2 mit Bohrdr?hten adaptiert. Das verletzte Bein wurde für 14 – 53 Wochen post trauma vollst?ndig entlastet. Die Beobachtungszeit betrug mit einer Ausnahme 2 Jahre oder mehr; 4 Patienten zeigten am letzten R?ntgenbild einen intakten Talus, 4 Patienten zeigten partielle Einbrüche des Talusdoms und in 1 Fall war ein Teileinbruch fraglich. Die histologische Untersuchung (16 – 52 Wochen post trauma) zeigte in allen F?llen osteozytenfreien origin?ren Knochen mit Anlagerung neuen Knochens in individuell recht unterschiedlichem Ausma?. Das Hawkins-Zeichen war in 6 F?llen partiell positiv, sowie je einmal positiv und einmal negativ. Im CT konnte sowohl Dekalzifikation als auch Frakturheilung besser als im R?ntgenbild beobachtet werden. Das MRT-Signal war 5mal normal, 2mal partiell und einmal komplett pathologisch. Positives Hawkins-Zeichen und normales Signalverhalten sind prognostisch günstig zu werten. Es kam jedoch in Folge zentraler Talusfraktur auch bei radiologisch günstigem Verlauf zur Osteonekrose wenigstens von Teilen Talus gefolgt von schleichendem Ersatz. Die offenbar bei jeder zentralen Talusfraktur gest?rte Vaskularisation wurde von keinem radiologischen Befund einwandfrei reflektiert.      

Synthese neuer Indolmethanamine durch Leimgruber-Batcho Reaktion

Synthesis of New Indolemethanamines Using the Leimgruber-Batcho Reaction A short and efficient synthesis of the title compounds is reported starting with commercially available carboxylic acids 1 and 5 , respectively. By appropriate modifications in the course of the Leimgruber-Batcho reaction used in the key step quite stable 1-hydroxy-indole derivatives became available.