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The exact differential diagnosis of iron overload syndromes is mandatory as important therapeutic consequences may derive from a correct diagnosis, especially when hemochromatosis is present. To facilitate diagnostic and therapeutic decisions algorithms and probabilistic calculations based on different frequencies of clinical symptoms and typical laboratory findings of the diseases in question have been proposed. Overestimation and/or underestimation of clinical symptoms and/or laboratory findings in using such calculations, however, may lead to incorrect diagnosis and therapy as demonstrated in this case. We report on a 62-year-old patient with arthralgia, pathologic glucose metabolism, brown skin pigmentation and excessively elevated ferritin and transferrin saturation levels, which initially were interpreted as signs of the assumed underlying disease (hemo-chromatosis) based on a high initial suspicion level and further corroborated by Bayesian probability analysis yielding a probability 99.0 % for the presence of hemochromatosis. Because of this high probability and the patient's wish for treatment phlebotomy was started, but stopped after having obtained negative results of genetic testing and normal quantitative liver iron values. The diagnosis of hemochromatosis had to be revised and symptoms and laboratory findings of this patient were found to be compatible with chronic fatty liver and pathologically altered iron metabolism due to chronic alcohol intake which the patient has initially concealed. The joint pain was explained in terms of chronic degenerative bone destruction, the impaired glucose tolerance seen as the consequence of obesity and the skin pigmentation was ascribed to sun exposure due to the patient's outdoor activities as a hobby farmer not evaluated during initial presentation. The implications and importance of unbiased history taking, critical interpretation of clinical symptoms and laboratory findings in using probabilistic calculations and diagnostic decision analysis are emphasized and the different mechanisms of iron metabolism in hemochromatosis and hemosiderosis are discussed.

trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or beta-cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by beta-cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical.

The exact differential diagnosis of iron overload syndromes is mandatory as important therapeutic consequences may derive from a correct diagnosis, especially when hemochromatosis is present. To facilitate diagnostic and therapeutic decisions algorithms and probabilistic calculations based on different frequencies of clinical symptoms and typical laboratory findings of the diseases in question have been proposed. Overestimation and/or underestimation of clinical symptoms and/or laboratory findings in using such calculations, however, may lead to incorrect diagnosis and therapy as demonstrated in this case. We report on a 62-year-old patient with arthralgia, pathologic glucose metabolism, brown skin pigmentation and excessively elevated ferritin and transferrin saturation levels, which initially were interpreted as signs of the assumed underlying disease (hemo-chromatosis) based on a high initial suspicion level and further corroborated by Bayesian probability analysis yielding a probability 99.0 % for the presence of hemochromatosis. Because of this high probability and the patient's wish for treatment phlebotomy was started, but stopped after having obtained negative results of genetic testing and normal quantitative liver iron values. The diagnosis of hemochromatosis had to be revised and symptoms and laboratory findings of this patient were found to be compatible with chronic fatty liver and pathologically altered iron metabolism due to chronic alcohol intake which the patient has initially concealed. The joint pain was explained in terms of chronic degenerative bone destruction, the impaired glucose tolerance seen as the consequence of obesity and the skin pigmentation was ascribed to sun exposure due to the patient's outdoor activities as a hobby farmer not evaluated during initial presentation. The implications and importance of unbiased history taking, critical interpretation of clinical symptoms and laboratory findings in using probabilistic calculations and diagnostic decision analysis are emphasized and the different mechanisms of iron metabolism in hemochromatosis and hemosiderosis are discussed.

In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity.

Primary cardiac tumors in infancy and childhood are extremely rare. In the young age group the clinical symptoms often are variable and can make diagnosis difficult. Depending on the histological character and especially the localisation of the mass the clinical appearance may lead to the first diagnosis or at least to further investigation. While myocardial tumors (rhabdomyomas and fibromas) mainly cause rhythmic disturbances, the intracavitary tumors (like myxomas) frequently disturb hemodynamics. Echo-cardiography is the main diagnostic technique, followed by angiocardiography, computertomography and nuclearmagneticresonance imaging.

After repeated administration of trans-4-acetylaminostilbene to rats, DNA-bound metabolites accumulate to the greatest extent in liver and kidney, which are considered to be nontarget tissues for this carcinogen. To test whether the persistent DNA adducts represent procarcinogenic lesions, an initiation-promotion experiment was carried out using trans-4-acetylaminostilbene as an initiator and phenobarbital, DDT and diethylstilbestrol as promoters. In addition, partial hepatectomy was performed in some groups. Partial hepatectomy alone or in combination with promoters led to the formation of preneoplastic enzyme deficient foci, hyperplastic nodules and hepatoma in great yields. In addition, mammary tumors were observed with diethylstilbestrol promotion. The results support our proposal that aminostilbene derivatives produce procarcinogenic DNA-lesions in many, if not all, tissues and that secondary factors determine when and where tumors arise.

Two carcinogenic aromatic amines with different organotropism were tested for syncarcinogenic effects in rat liver in an initiation-promotion experiment. Trans-4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) were administered as initiators in four doses each either alone or sequentially combined in both orders. The promotion phase was started by partial hepatectomy and continued by adding phenobarbital (250 p.p.m.) to the drinking water for 26 weeks. The number/cm2 of tissue section and average size of hyperplastic foci, glucose-6-phosphatase-deficient and gamma-glutamyl-transpeptidase-positive foci were determined and a total area of lesions calculated during the promotion phase after 18 and 31 weeks, and in the post-promotion phase after 42 and 47 weeks. The synergistic effects of AAS and AAF were clearly more than additive if compared with the sum of the effects exerted by each compound individually. The sequence in which both initiators were administered remarkably influenced the development of lesions. They developed more rapidly and persisted longer in the post-promotion phase when AAS was administered first and AAF second. In the final stage, enzyme altered foci increased in the livers of both combination groups, but to a greater extent in the AAS-AAF group. It is concluded that the two arylamides damage DNA independently. In addition, however, the results suggest that AAS acts predominantly as an initiator, and AAF as a weak initiator and a strong promoter in what is considered the initiation phase of this experiment.

Das Krankheitsbild der chronischen Pharyngitis ist klinisch gut definiert, doch bislang nur ungenugend morphologisch abgeklart. In der vorliegenden Studie wurden deshalb bei zwolf Kindern mit chronischer Pharyngitis, die sich einer Adenotonsillektomie unterziehen musten, kleine Gewebsproben von der Rachenhinterwand lichtmikroskopisch untersucht. Dabei zeigte sich, das in den meisten Fallen entzundliche Infiltrate fehlten. Stets war eine mehr oder weniger ausgepragte Hyperplasie des lymphatischen Gewebes nachzuweisen. Bei starker Auspragung fand sich eine lymphoepitheliale Desintegration, die fur die klinische Symptomatik verantwortlich sein durfte und moglicherweise ein dispositioneller Faktor fur das Auftreten einer echten Pharyngitis darstellt. Die mikromorphologischen Veranderungen wurden in vier Stadien unterteilt.

Pure trichloroethylene (tri), stabilized by an amine base, was administered by inhalation at 0, 100, and 500 ppm for 6 h/day, 5 days/week, for 18 months to mice, rats and Syrian hamsters of both sexes. No significant increase in tumor formation was observed in any species or dosing group, except in malignant lymphomas, which were increased in female mice in the following incidence rates: 9/29 (controls), 17/30 (100 ppm), and 18/28 (500 ppm). Whether or not this high occurrence of lymphomas, which is peculiar to this strain of mice (NMRI) has any relationship to tri-exposure, cannot be decided upon by the present experiment. It is concluded that from these findings no indication for a carcinogenic potential of pure trichloroethylene can be deduced.

2 years of experience with the sphincteroplasty in colostomy as well as intensive histological studies have shown that gastrointestinal smooth muscle can be auto-transplanted without loosing functional or histological integrity. The following conclusions are based on experimental studies in dogs: (1) the sphincteroplasty technique can be successfully applied in ileostomy, and (2) the sphincteroplasty must, however, be combined with a pre-sphincter valve and an omega loop with Braun’s anastomosis. The first clinical results confirm this concept.

Es wird ein Fall mit funf eigenstandigen Tumoren vorgestellt: Fibro-sarkom am rechten Oberschenkel, Mammakarzinom beidseits, papil-lares Schilddrusenkarzinom, Basaliom links infraklavikular. Anhand ei

In vitro ist14C-Methyl-Phalloidin gut dialysabel; in vivo erwies sich dieser Effekt als ungleich geringer. Bei Ratten fuhrte die Applikation von 2 mg/kg Phalloidin i. v. nach 106 Minuten im Mittel zum Tode. Die Uberlebenszeiten wurden durch eine sofort eingeleitete Hamodialyse gegen Elektrolyt-Glukose-Losung bzw. Plasmaprotein gegenuber der Kontrollgruppe nur insignifikant verandert. Lediglich das Tierkollektiv, das unmittelbar nach Vergiftung gegen Partnertiere dialysiert wurde (Cross-Dialyse), zeigte eine statistisch insignifikante Verlangerung der Uberlebenszeit um 16 Minuten. Der histomorphologische Leberbefund war in allen Kollektiven gleich. Neben einer Phalloidin-spezifischen Vakuolisierung des Zytoplasmas der lappchenperipher gelegenen Hepatozyten und hamorrhagischen Nekrosen fanden sich eine feintropfige periphere Verfettung sowie Pyknosen. Spezifische Phalloidineffekte manifestierten sich auch in der Leber der bei Cross-Dialyse verwendeten Partnertiere.

Diabetic and senile glomerulosclerosis consists of thickening of the glomerular basement membranes (GBM) and augmentation of the mesangial matrix. The pathogenesis of these alterations is still controversial. Therefore, an in vivo study of the metabolism and the chemical composition of the GBM in streptozotocin-diabetic and old rats reported here was conducted: The turnover rate of the GBM, determined by the incorporation of labeled hydroxyproline, is prolonged in preparations from diabetic and aging rats. This can be explained by the decreased synthesis and delayed degradation of the GBM material found in both experimental groups. The biochemical analyses of the GBM revealed a higher content of hydroxylated amino acids, especially OH-lys, in the old and diabetic animals. The findings suggest that diabetic and senile glomerulosclerosis results from a prolonged turnover of the GBM and GBM-like material under the altered metabolic conditions investigated in this study.

An autoradiographic study of the proliferative response of the cells of the Macula Densa days or months after the removal of 5/6 of the rat's kidney has shown that these cells are capable of division. The index of labelling of these cells is considerably lower than that of the other cells of the distal tubules. This applies of the kidney of normal controls and to the remnant after partial nephrectomy, shortly after operation as well as several months later. The cells of the Macula Densa therefore seem to represent a more stable population in the nephron. They therefore differ from the other cells of the distal tubules not only in appearance and function, but also in the pattern of cell proliferation.

The effects of streptozotocin diabetes on the collagen metabolism in rat glomerular basement membrane (GBM) have been investigated. The metabolic activity was measured in vivo by following the incorporation of 3H-proline into hydroxyproline over the course of 3 months. Under diabetic conditions, smaller amounts of labeled hydroxyproline were found in the GBM indicating that collagen synthesis is injured. The retarded disappearance of the tracer from the GBM is related to an additional alteration of the degradation resulting in a slower turnover. If collagen formation is reduced in streptozotocin diabetes, the thickening of the diabetic basement membranes can only explained by this disturbed catabolism. The amino acid composition of GBM was also altered after streptozotocin application. The diabetic animals showed an increase of hydroxylysine in this structure. The diabetic effects on the GBM presented were interpreted as a kind of accelerated aging of collagen.

There is evidence that the rarefaction of the capillary bed is typical for the skeletal muscle of spontaneously hypertensive rats. We were therefore interested to learn whether there is also a rarefaction in skeletal muscle of human hypertensives. The number of capillaries was morphometrically analysed and counted in the quadriceps and the pectoralis major muscles of human normotensives (n = 12) and hypertensives (n = 15). The clinical diagnosis and certain pathological criteria, such as blood pressure (with or without antihypertensive therapy), heart weight, left ventricular wall thickness, the state of kidney arterioles and brain, and heart vessels, were used to classify the patients into two groups. The dissected tissue samples were prepared according to the GMA method and the capillary numbers per area were counted using light microscopy (250 x). The quadriceps muscle had a capillary density (per 2.5 mm2) of 442 +/- 51 in normotensives and 277 +/- 41 in hypertensive patients; in the pectoralis major muscle we counted 477 +/- 30 in controls and 232 +/- 28 in hypertensives. The rarefaction in the quadriceps muscle ranged by about 37%, in the pectoralis major muscle by about 51%. It is suggested that the reduction of the capillary surface area caused by the capillary rarefaction reduces the transcapillary fluid exchange and in that way prevents an overperfusion of the terminal vascular bed.

An funf weisen Miniaturschweinen wurden umschriebene drittgradige Verbrennungen gesetzt. Die plastische Deckung nach Escharektomie erfolgte mit gemischt homolog/autologen Transplantaten. Diese waren im Unterschied zur chinesischen Technik homologe Vollhauttransplantate, welche zuvor in einer herkommlichen Gefriertruhe gefrierkonserviert (−27°C) worden waren. Die Versuche erbrachten bei samtlichen Tieren eine rasche Epithelialisierung, gute kosmetische und klinische Ergebnisse.

The differentiation of the thyroid glands follicular neoplasias into adenomas and carcinomas is currently done using the histological criteria recommended by WHO. This pilot study of 10 human follicular carcinomas and 10 folliculars adenomas demonstrates the possibility of a cytological classification using digital picture processing of high resolution cell images. Giemsa stained paraplast sections were scanned with a Colour-TV-camera, different channels were used with respect to staining and analyzing methods and computed with an image processing system. The computer aided cytophotometric methods detected significant differences in the chromatin arrangement and structure.

The necrolytic activity of bromelain was tested on 3rd degree burns in rats. Using a 35% concentration of the enzyme in a lipid base, complete and selective debridement was observed within 24 h. No ge

Although Osterby and coworkers have shown that the onset of diabetes is associated with glomerular hypertrophy and enlargement of the filtration surface, the pathogenesis of this lesion and the behaviour of the glomerular tuft cells during the increase in glomerular filtration surface area remain unclear. Autoradiography and electron microscopic morphometry in kidneys of male Sprague-Dawley rats with streptozotocin-induced diabetes indicate that glomerular enlargement is combined with glomerular cell hyperplasia. 6 days after continuous 3H-thymidine infusion there is a significant increase in DNA-synthesis in tuft cells indicating cell proliferation. Since podocyte volume only increases in acute diabetes (as shown by Osterby and Gundersen in 1980), and the mean podocyte nuclear area remains unchanged, we conclude that the increased DNA-synthesis results in podocyte hypercellularity so that an increased glomerular filtration surface area can be covered by a greater number of cells.

Die Glomerulosklerose, die sich als Folge einer diabetischen Stoffwechselstorung entwikkelt, ist gekennzeichnet durch eine gleichformige Verbreiterung der glomerularen Basalmembran (GBM) und eine Zunahme der mesangialen Matrix. Beide Veranderungen beginnen schon wenige Jahre nach dem Auftreten des Diabetes und betreffen anfangs alle Glomeruli in gleichem Mase (=diffuse Form). Spater treten im Mesangium noch kugelige Glycoproteinablagerungen auf (=nodulare Form), die allein fur den Diabetes spezifisch sind. Daneben beobachtet man stets Plasmainsudationen an den vasa afferentia und efferentia sowie an den Kapillarschlingen. Die Zunahme der GBM-Masse und des GBM-ahnlichen Materials im Mesangium ist pathogenetisch noch nicht hinreichend geklart. Der Grund sind widerspruchliche Angaben zum Stoffwechsel und zur chemischen Zusammensetzung der GBM beim Diabetes. Biochemische, enzymhistochemische und Tracerstudien an Nieren oder isolierten Glomeruli von Diabetikern und diabetischen Nagern haben bislang Hinweise auf eine Synthesesteigerung (anabole Storung) wie auf eine Abbauhemmung (katabole Storung) erbracht. Diese Ubersichtsarbeit stellt die divergierenden Ansichten zur Diskussion und versucht, mogliche Ursachen fur die gegenwartigen Diskrepanzen aufzuzeigen.

L-Sorbose wird bei einem Pegel von 10 % in einer Casein-Stärke-Diät an wachsende Ratten beider Geschlechter verfüttert und mit D-Glucose verglichen. Insulinspiegel im Plasma sind nach Sorbose signifikant erniedrigt. Wachstumsgeschwindigkeit, Protein efficiency ratio, Blutzucker, freie Fettsäuren im Plasma und Histologie der Organe sind in den Sorbose- bzw. Glucosegruppen nicht signifikant verschieden. Die Caecumgewichte sind erhöht und zeigen neben der Ausscheidung von etwa 10 % der Dosis im Urin an, daβ L-Sorbose im Organismus nur begrenzt unter Mitwirkung der Darmbakterien genutzt wird. Leber -gewichte, Lactatdehydrogenase im Plasma und der Prozentsatz eosinophiler Zellen unter den weiβen Blutkörperchen sind hochsignifi-kant erhöht nach Verfütterung von Sorbose. Die Lebensmittel-sicherheit von L-Sorbose fordert sehr gründliche weitere Studien, bevor die uneingeschränkte Verwendung von L-Sorbose für die Er-nährung des Menschen empfohlen werden kann.

Experiments on bastard dogs have shown that cardia reconstruction using an omega sling is effective. This sling is a pedicled, extramucosally excised, longitudinal muscle flap from the ventral aspect of the greater gastric curvature, which is prestretched at least 100%, wrapped around the cardia twice and sutured to the posterior gastric wall. A physiological pressure gradient is created with the help of intraoperative manometry. Perfusion manometry, radiology, histology and microangiographs demonstrate the competence of the omega sling.

Wenn man mit Antimetaboliten die RNS- und Proteinsynthese unterbindet, verandert der Nukleolus sein Aussehen. Dabei treten bei der elektronenmikroskopischen Betrachtung ganz unterschiedliche Nukleolusalterationen auf, je nachdem, wo die Synthesekette unterbrochen worden ist. Wenn die Transkription an der DNS gestort ist, kommt es zu einer Trennung der einzelnen Nukleoluskomponenten, zur Segregation. Bei Transformations- (Reifungs-)storungen nehmen die Fibrillen des Nukleolus stark an Zahl zu, die Granula verschwinden dagegen nahezu vollig. Der umgekehrte Vorgang ist zu beobachten, wenn die nukleolare Stoffabgabe blockiert ist (=Transmissionsstorung): der Nukleolus besteht hier fast nur noch aus Granula und ist stark vergrosert. Translationsstorungen haben keinen unmittelbaren Einflus auf das Aussehen des Nukleolus. Erst wenn die Bildung der mRNS langere Zeit unterbunden ist, schrumpft der Nukleolus und verarmt an Granula. Die Kenntnis der morphologischen Nukleolusbefunde nach Gabe von Inhibitoren der RNS-Synthese mit klar definiertem Wirkmechanismus sollte es gestatten, ahnliche Nukleolusveranderungen — etwa bei Krebs- und Virus-infizierten Zellen — auf molekularbiologischer Basis zu deuten.

ZusammenfassungEingangs wird das Prinzip eines 131J-Trijodthyronin-in-vitro-Tests (131JT3-Test), der den Kationenaustauscher Amberlite CG 50 II benützt, beschrieben. Methodische Untersuchungen zu diesem Test hatten folgende Ergebnisse:1. Auf eine Vorinkubation des Serum-131 JT3-Gemisches kann nicht verzichtet werden. 15 min sind hierfür ausreichend.2. Das Alter von verschlossenen, kühl gelagerten Seren beeinflußt den Test während der beiden, auf die Blutabnahme folgenden Tage nicht. Am 3. und 6. Tag danach wird eine leichte Erhöhung der Werte beobachtet.3. Die Abhängigkeit der 131JT3-Aufnahme vom pH-Wert des Blutes wird untersucht. Im physiologischen pH-Bereich wird die Schwankungsbreite der Wasserstoffionenkonzentration durch eine Pufferung des Inkubationsgemisches nur unwesentlich verringert. Deshalb verzichten wir auf die Verwendung einer Pufferlösung.4. Bei Durchführung des 131JT3-Tests im offenen System tritt in Fällen von CO2-Retention ein allmählicher CO2-Ausgleich und damit eine Eliminierung dieses Störfaktors ein.5. Eine mehr oder minder starke Anlagerung des 131JT3 an Glaswaren läßt sich kaum vermeiden. Bei der Durchführung des Tests in der von uns angegebenen Weise tritt hierdurch jedoch keine Verfälschung der Ergebnisse ein.

The mitoses of hepatocytes and hepatoma cells were examined qualitatively and quantitatively after continuous (“continuous” experiment) or temporary limited (“stop” experiment) treatment with different concentrations of the hepatocarcinogen Nitrosomorpholine (NNM) (12 mg and 50 mg NNM ad 100 ml drinking water). The mitotic index of the parenchyma is increased in all experiments, especially during the administration of the 50mg-% NNM-solution, which also caused the most extensive necroses. In the “stop” experiment the mitotic rate lies in the same dimension as the rate of the necrosis, except from a transient rise 4 weeks after the removal of the carcinogenic stimulus. Only when hepatomas appear, do the dividing cells increase considerably in number.

Der auf Grund zahlreicher Beobachtungen beim Menschen vermutete Kausalzusammenhang von Nierenvenenthrombose und nephrotischem Syndrom wurde experimentell uberpruft. Bei 30 Ratten wurde durch subtotale Ligatur der linken Nierenvene eine partielle bis totale Thrombosierung des Gefaslumens erzeugt, die nachfolgende Proteinurie und Dysproteinamie sowie die licht- und elektronenmikroskopisch sichtbaren Veranderungen am Glomerulus in wochentlichen Abstanden bis zu einem halben Jahr kontrolliert. Im Anschlus an die Drosselung entwickelte sich eine hochstens mittelgradige, nur einige Wochen andauernde Proteinurie und gelegentlich eine leichte Hypoalbuminamie und Dysproteinamie. Der renale Eiweisverlust ist nach den am Glomerulus erhobenen Befunden auf den erhohten Filtrationsdruck und vor allem auf hypoxische Schaden der fur den glomerularen Filter verantwortlichen visceralen Deckzellen zuruckzufuhren. Es konnte nicht das Bild der sog. „membranosen Transformation“ erzeugt werden, das bei den Fallen von menschlicher Nierenvenenthrombose mit nephrotischem Syndrom an den Capillarschlingen auftritt und mit den Veranderungen bei der membranosen Glomerulonephritis identisch ist. Es wird daher die Vermutung geausert, das ein voll ausgebildetes nephrotisches Syndrom bei Nierenvenenthrombose des Menschen nicht Folge, sondern entweder akzidentelles Begleitphanomen oder sogar Ursache der Nierenvenenthrombose ist.

Nach i.v.-Injektion von 4mal 50 mg 10%iger Ferritinlosung innerhalb von 3 Tagen geben viele Zellen des Rindeninterstitiums (i.Z.) der Rattenniere eine kraftige, vorwiegend granulare Turnbullblau-Reaktion. Elektronenmikroskopisch zeigt sich, das das Ferritin in Zellen gespeichert ist, welche zwischen der capillaren und tubularen Basalmembran liegen. Die Ferritinmolekule gelangen direkt aus den postglomerularen Capillaren in den interstitiellen Raum und von dort in die i.Z., wo sie in Vacuolen oder frei im Grundplasma zu finden sind. Neben diesen ferritinspeichernden i.Z. sind die schon langer bekannten fibrocytaren Zellformen des Rindeninterstitiums nachzuweisen. Auserdem werden Mischformen aufgezeigt, welche die Annahme zulassen, das es sich bei den i.Z. um bi(oder multi-)funktionelle Zellen handelt, die je nach den Erfordernissen vorwiegend histiooder fibrocytare Eigenschaften entfalten und wahrscheinlich reversibel unter Ausbildung von Zwischenformen ineinander ubergehen konnen. Die Mesangiumzellen des Glomerulus und die i.Z. des Nierenmarkes zeigen ein grundsatzlich gleiches Verhalten. Daraus wird gefolgert, das die Niere uber ein interstitielles fibro-histiocytares Zellsystem verfugt, das — mit einigen standortbedingten Varianten — einer einheitlichen Betrachtung zugangig ist.

Bei 100 einzeitig 5/6-nephrektomierten Ratten wurde unter regelmasiger Kontrolle von Serumharnstoff-N, Serumelektrolyten, Harnmenge und renaler Eiweisausscheidung 1, 2, 3 und 4 Tage sowie 1, 2, 3, 6, 9, 12, 15, 20 und 25 Wochen post op. das verbliebene Nierenparenchym von jeweils 4 Tieren lichtmikroskopisch untersucht. Die morphologischen Veranderungen lassen sich 3 Phasen zuordnen: I. Phase des akuten Schadens, II. Phase der kompensatorischen Nierenvergroserung und III. Phase der Spatschaden. In der 1. Phase (1. postoperative Woche) treten infolge des operativen Eingriffes und der Traumatisierung des Parenchyms viele Einzelzellnekrosen im gesamten Nephron, vereinzelt sogar kleinere inkomplette bis komplette Infarkte auf. Die 2. Phase, die ungefahr vom 2. Tag bis zur 6. Woche post op. dauert, ist anfangs durch zahlreiche Mitosen besonders in den proximalen Tubuli, spater durch eine kraftige Hypertrophie der Nierenkorperchen und der Nierenkanalchen gekennzeichnet. Die Restniere kann dabei um das 5–6fache schwerer werden. Damit ist eine Steigerung der Resorptions- und Sekretionskapazitat des tubularen Apparates verbunden, die jedoch offenbar hinter der Erhohung des Ultrafiltrates zuruckbleibt, so das Polyurie, Azotamie und Salzverlust resultieren. In der Phase der Spatschaden (9.–25. Woche post op.) entwickeln alle Ratten eine Glomerulosklerose, die mit einer uber die Norm gesteigerten Proteinurie einhergeht. Gelegentlich findet man daneben eine hochdruckbedingte Arteriolosklerose mit nachfolgenden glomerularen Schaden sowie (pyelo-)nephritisch bedingte Veranderungen am tubularen Apparat und den Glomeruli.

Mit der alternierenden intratubularen Ferritin-Ol-Injektion (Modifikation der Methode der gespaltenen Olsaule) wurde der Ablauf der Eiweisresorption wahrend der vacuolaren Phase im proximalen Tubuluskonvolut der Rattenniere untersucht. Die Resorptionszeiten lagen zwischen 1 und 31/2 Std. Als lysosomales Leitenzym wurde saure Phosphatase (acPase) cytochemisch dargestellt. Im Mittelpunkt stand die Frage nach dem Mechanismus der Kontaktaufnahme zwischen resobiertem Eiweis und lytischen Enzymen.

The experimental thrombosis of the renal vein of the rat usually leads to renal atrophy. Tubules appearing chromophobic in the light microscope with routine staining methods occur in the cortex of the contracting kidney after the 5th week. They are composed of epithelial cells which contain acid mucopolysaccharides as demonstrated by histochemical reactions. By electron microscopy, numerous membrane bound vacuoles are demonstrable in their cytoplasm; they are either optically empty or show a lamellar composition. The clear regions presumably contained mucopolysaccharides, whereas the elements of the lamellar component are presumably lipoids. These lipoids show frequently a characteristic linear pattern with a period of 5–6 nm. The vacuoles resemble the so-called zebrabodies found in human gangliosidoses and certain mucopolysaccharidoses.

An funf Gottinger Miniaturschweinen wurden umschrieben drittgradige Verbrennungen gesetzt. Die plastische Deckung erfolgte nach Escharektomie mit gefrierkonservierten heterolog/autolog gemischten Vollhauttransplantaten. Die Gefrierkonservierung der heterologen von Makaken gewonnenen Vollhaut war in einer herkommlichen Gefrierkuhltruhe bei −27°C erfolgt. Eine beschleunigte oder gar vollwertige Epithelialisierung, wie sie z. B. in den chinesischen Arbeiten beschrieben ist, konnte nicht beobachtet werden. Die Heilung erfolgte unter Bildung eines Narbenareals, welches etwa die Halfte der ehemals verbrannten Flache betrug.

Comparing the morphological effects of actinomycin D and alpha amanitine on the rat liver, it can be seen that the nuclear alterations caused by actinomycin (=segregation of the nucleolus and condensation of all the chromatin) occur simultaneously. After treatment with amanitine, the lesions appear in two steps. First of all one sees condensation of only the extranucleolar chromatin and fragmentation of the nucleolus. These two phenomena are related to each other not only chronogically but also causetively. In our opinion the shrinkage of the extranucleolar parts of chromosones results in the individual nucleolus-organizers being removed into different quarters of the nucleoplasm. The fragments themselves must not be altered structurally and functionally, as Kedinger and Simard (1974) have already shown. We always observed changes of the nucleolar fragments 30-90 min after the fragmentation. These changes consisted of the condensation of the intranucleolar chromatin, and the segregation and degranulation of the nucleolus, in the same manner found directly after the actinomycin-poisoning in the whole nucleolus. The delay of the lesions observed on the dispersed nucleolar fragments indicates that is a consequence of the amanitine-poisoning -- probably the result of the disturbed protein synthesis and the inactivation of a hypothetical extranucleolar regulatorgene, which controls nucleolar function.

Permanent nerve blocks by intraneurally injected alcohol are often complicated by alcohol-neuritis. Encouraging clinical experiences with permanent blocks by freezing raises the question whether morphological differences between the nerve lesions could explain the difference in their side effects. On 30 rabbits both sciatic nerves were blocked after surgical preparation. The one by intraneural injection of 0,5 ml of 96% Ethanol, the other by freezing with a cryoprobe. The resulting degeneration and the beginning of recovery of the nerves was followed by histological evaluations of the sciatic nerves during the first 28 days after the blockade. The nerve lesions of both types of blockade were complete. That produced by the cryoprobe was limited to the small area of local freezing, whereas the alcohol-block produced the same type of nerve degeneration but with a wide-spread extension reaching the sacral plexus. We discuss whether this slight morphological difference might be sufficient to explain the higher complication rate of alcohol blocks.

The acute toxicity of the carcinogen trans-4-dimethylaminostilbene was studied in Wistar rats. The animals die after oral administration of 50 mg/kg (LD50) with a latency period of 11 days. Specific lesions of the stomach epithelium together with acute bone marrow incapacity and toxic effects on peripheral blood cells lead to acute anemia, which is considered to be the cause of death. Histological observations indicate that the stomach lesions develop in three phases. Firstly, necroses appear in the proliferative area predominantly in the antrum. This leads, secondly, to cystic transformation of the antrum, cardia, and Brunner's glands and further to peptic erosions and ulcerations. Thirdly, mitotic activity increases. With lethal doses, cell replacement remains incomplete. There ist a correlation between the proliferation rate of different cell types and their susceptibility; but this cannot entirely account for the tissue-specific, systemic effects of trans-4-dimethylaminostilbene. Metabolic activation is also involved, since enzyme induction with methylcholanthrene inhibits toxicity. The study disclosed a new target tissue which may now be used to investigate the mechanism of action of reactive metabolites of an aromatic amine in acute experiments. The same stomach lesions were also observed with adriamycin. With this compound, however, the intestine is also involved.

The tissue distribution of intravenously injected native and enzyme-treated human gammaglobulin has been investigated in human rectum mucosa. FITC-labelled antibodies to human gammaglobulin were used to locate the injected antibody preparation. Three hours after application of these different gammaglobulin-preparations no enrichment in the mucosa was found. Neither the native gammaglobulin nor the enzyme-treated gammaglobulin showed any concentration in the lamina propria of the large bowel mucosa or an intracellular enrichment in the epithel. This study shows that the quicker elimination of enzyme-treated gamma-globulin from the circulation cannot be explained by an intracellular increase.