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In cells treated with antimetabolites to inhibit RNA- and protein synthesis, electron microscopic studies reveal structural alterations of the nucleolus. The morphological appearance of the nucleolus differs depending of the inhibitor used. If transcription is prevented, segregation of nucleolar components is observed. Inhibition of processing of newly synthesized RNA results in a degranulation and an increase in the amount of nucleolar fibrils. A disturbance of the release of nucleolar ribonucleoproteins into the cytoplasm leads to an enlargement and a hypergranulation of the nucleolus. On the other hand interruption of translation of mRNAs has no immediate effect on the appearance of the nucleolar structure. Only after longer treatment of the cells with the translation inhibitor the nucleolus shrinks and becomes degranulated. The use of inhibitors with clearly defined mechanisms of action in a morphological study should make it possible to interpret similar nucleolar alterations seen in cancer cells and virus-infected cells on a molecular biological basis.

Nach Meinung zahlreicher Experten sind marine Nahrungsquellen bisher nur ganz sporadisch untef den strikten Bedingungen eines 90 Tage-Versuches (1) untersucht worden. Da unter diesen Umstanden der Wahl einer Kontrolldiat ganz besondere Bedeutung zukommt (Casein?, mit Methi oninerganzung?, Vollei?, Fischmehl?) haben wir uns entschlossen, als Kontrolle sowohl ein technologisch vergleichbar gewonnenes Material aus Nordseegarnelen, als dem nachsten Verwandten des Krill mit gutter Erhaltlichkeit, als auch ein kommerziell verfugbares Fischmehl (ohne Zusatz von Antioxydans) zu verwenden.

75 male rats were given toxic dosage of the hepatotoxin N-nitrosomorpholine (NNM) using varied concentrations over varied time intervals. During and after the toxic dosings the kidneys were examined by light and electron microscopy in order to decide, whether the kidneys are also damaged by NNM. Our studies reveal that under the influence of a low concentration of NNM a distinct thickening of the GBM and an increase of the mesangial matrix occurs (changes referred by us as glomerulosclerosis). When a high concentration of NNM was given, toxic lesions of the mesangial and epithelial cells of the glomeruli were found, but a glomerulosclerosis was not observed during the intoxication. After this toxic dose was stopped, however, a progressive glomerulosclerosis did develop, which at first was accompanied by a transient proliferation of the mesangial cells.

Mit einer Mortalitatsrate von 30% [1] ist die Prognose der Knollenblatterpilzvergiftung sehr ernst. Therapeutisch wird von klinischer Seite die Hamodialysebehandlung innerhalb der ersten 24 Std nach Pilzgenus gefordert [4, 5, 6, 7, 8]. Ob durch diese Masnahme tatsachlich die Prognose entscheidend gebessert wird, mus auf Grund jungster tierexperimenteller Untersuchungen von Fauser u. Faulstich [2, 3] ernsthaft bezweifelt werden. An amanitinvergifteten Hunden stellten die Autoren fest, das bereits innerhalb von 6 Std, d. h. noch wahrend des klinischen Latenzstadiums, 85% des Toxins renal eliminiert ist. Der Amanitin-Plasmaspiegel liegt zu dieser Zeit bereits unter der Grenze der Nachweisbarkeit, so das eine Dialysebehandlung ineffektiv erscheinen mus.

Using autotransplants of an autonomous intestinal muscle segment a sphincter substitute and consequently a continent colostomy can be produced in humans and dogs. The histological study of the intestinal muscle section resected 1--28 weeks after implantation shows, in dogs, a good healing process and vascularization of the transplant muscle, which explains the clinical success. Even after many weeks only slight atrophy and fibrosis can be observed. Only a few of the intramural nerve plexuses perish. Some of the small intestine sphincters remain incontinent. The specimens show a more or less extensive hemorrhagic necrosis of the transplant with high inflammation. The reason for these complications is thought to be the mucosa glands, which were not completely removed from the vulnerable small intestine of the dog before the transplantation.

A case of human rabies is reported showing a peculiar course in some respects. The lack of a satisfactory history concerning an animal bite 5 months earlier as well as a misleading psychiatric history led to difficulty and delay in reaching a diagnosis. Under intensive care, including mechanical ventilation and cardiac pacing, the disease reached a final stage, which is rarely seen. The clinical course and the pathological findings are described in detail and the etiology and prognosis of the disease are discussed. The latter remains rather hopeless de spite modern intensive care.

Zur Therapie inkontinenter Hohlorgane stehen bisher im wesentlichen zwei Methoden zur Verfugung: Einmal, mechanische Verschlusse wodurch man jedoch in der Regel nur eine Stenose ohne sehr befriedigende Kontinenzleistung setzt, zum anderen dient die Skeletmuskulatur als Sphincterersatzmaterial.

In touch preparations and tissue sections from normal rat hepatocytes and alpha-amanitine- and actinomycin D-poisoned liver cells the extent of chromatin condensation relatively to the degree of ploidy and the chromatin distribution were studied by means of computer aided cytophotometry. It could be found, that the relationship of the condensed and decondensed chromatin is independent of the degree of ploidy and first of all dependent upon the intoxicant. Therefore, the extent of chromatin condensation can be utilized also in sections as additional parameter for automated cell screening.

In 5 white piglets 3rd-degree burns were applied. After escharectomy the wound-dressing was done by intermingled homo/autografts. In variation of the Chinese method reported, in our experiments the homografts consisted of full-thickness skin preserved by freezing (-27 degrees C). In all piglets this procedure caused a perfect epithelialization and brought good cosmetic and clinical results.

Nocardial sepsis occurred after aortic valve replacement in two patients. A septic suture aneurysm of the aortotomy was resected and the prosthesis exchanged in one of them. The other received conservative treatment for sternal osteomyelitis and local mediastinitis. Clinical cure was followed by relapse and death from cerebral infarction, and necropsy revealed a septic suture aneurysm of the aortotomy. Radical surgical revision seems to be necessary for lasting cure in such infections.

In 10 patients with severe pain localised over the dorsal aspect of the lunate, the capsule of the wrist joint was exposed and fenestrated over the scapho-lunate ligament. In two cases flat ganglion cysts were found, too small to be palpated before surgery. In the other 8 cases without macroscopically visible changes, histologically, areas of mucoid degeneration and very small ganglion cysts could be seen in the capsule. All patients were pain free after surgery. It is concluded that very small intracapsular cysts in the area of the dorsal scapho-lunate ligament, the most common origin of ganglia, may irritate the posterior interosseus nerve which is located in this area.

Previous analytical studies of industrial samples of trichloroethylene (TRI) have revealed the presence of mutagenic and carcinogenic epoxides which, it was proposed, might be responsible for the carcinogenicity of such samples, as demonstrated with mice in other laboratories. To test this hypothesis, Swiss mice (ICR/HA) of both sexes, bred and kept in SPF conditions, were dosed daily with TRI in corn oil by gavage (males: 2.4 g/kg, females: 1.8 g/kg) with or without the addition of epichlorohydrin (EPC, 0.8%, w/w), 1,2-epoxybutane (BO, 0,8%), or EPC + BO (0.25% + 0,25%) for 18 months. The ensuing observation period terminated at 106 weeks (from start of experiment). Gross and microscopic examination of all organs revealed a statistically significant increase in the incidence of forestomach papillomas and carcinomas after EPC-, BO-, and (EPC + BO)-stabilized samples of TRI, but not after pure, amine base-stabilized TRI. This type of tumor is believed to be induced by the direct alkylating epoxides epichlorohydrin and epoxybutane, whose industrial use in stabilizing chlorinated aliphatic hydrocarbons should be discontinued. No other significant increase in tumor incidences was found. Again, this study does not support the suggestion that trichloroethylene itself is carcinogenic under realistic exposure conditions.

On five minipigs third-degree burns were applied. The surgical skin coverage was established after escharectomie by freeze-preserved heterological/autological intermingled full-thickness skin grafts. The freeze-preservation of the Makaka-skin (full-thickness skin) was achieved in a commercially available freezer at -27 degrees C. We could not observe a accelerated or even complete re-epithelialization as it is described in the Chinese papers. The burnwunds healt in form of scare areas covering about half of the previously burned area.

Kardiovaskulare Todesursachen sind heute in der Mortalitatsstatistik des chronischen Nierenversagens fuhrend. Neben morphologisch augenfalligen Ursachen des Herzversagens wie Perikarditis und Calcifikationen im Myokard [9] ergaben sich in letzter Zeit Anhaltspunkte fur die Existenz einer eigenstandigen uramischen Kardiomyopathie, die zumindest im Tierversuch nur unter Ruhebedingungen larviert sein soll. Riecker et al. [6] fanden bei Uramie erst nach Stimulation mit Isoproterenol eine Verminderung der kontraktilen Leistungsreserve des Herzmuskels. Nach Ansicht der Autoren ist eine Teilerklarung des Kontraktilitatsschwundes die begleitende Hyperkaliamie.

Following oral pretreatment with rifampicin over 3 and 9 days, the exocrine pancreatic function was studied in urethane-anaesthetized rats under exocrine stimulation. The volume and electrolyte content, and especially the protein and amylase outputs of the pancreatic secretion showed a virtually dose- and time-dependent decrease. Histologically, there was a corresponding decline of the zymogen granules in the acinar cells. The suggested explanation for the observed disorders of the pancreatic exocrine function is primarily an inhibition of protein synthesis due to rifampicin.

75 male rats were given toxic dosage of the hepatotoxin N-nitrosomorpholine (NNM) using varied concentrations over varied time intervals. During and after the toxic dosings the kidneys were examined by light and electron microscopy in order to decide, whether the kidneys are also damaged by NNM. Our studies reveal that under the influence of a low concentration of NNM a distinct thickening of the GBM and an increase of the mesangial matrix occurs (changes referred by us as glomerulosclerosis). When a high concentration of NNM was given, toxic lesions of the mesangial and epithelial cells of the glomeruli were found, but a glomerulosclerosis was not observed during the intoxication. After this toxic dose was stopped, however, a progressive glomerulosclerosis did develop, which at first was accompanied by a transient proliferation of the mesangial cells. The glomerular changes found in the course of poisoning with NNM were interpreted as a direct effect of the NNM. From studies of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that the poisoning leads to a decrease in breakdown of the components of the basement membrane and the mesangial matrix, thus causing the widening of the GBM and the augmentation of the mesangial matrix.

Experimental and clinical investigations (92 patients) of a novel continent colostoma sphincter plasty are presented with particular evaluation of the histology of the autografted sphincter plasty. In

In five infants with autosomal aberrations and diminished resistance to infection (in spite of intact humoral and cellular immune mechanisms) several granulocyte functions (chemotaxis, phagocytosis, intracellular killing and metabolism of killing) were measured. A serum-dependent or a cell-dependent disturbance of phagocytosis of Candida albicans was found in two infants with cat-cry syndrome and one with trisomy 18. In one of these children there was an additional serum dependent defect of the killing of Candida albicans and of Staphylococcus aureus, serum levels of opsonins (IgG, IgM, CH50 and C3) being within normal range. An infant with trisomy 21 showed, in addition to a cellular defect of chemotaxis, a reduced cellular ability of the killing of Staphylococcus aureus and of Escherichia coli in autologous and AB-pool-serum. Phagocytosis of these bacteria remained normal.

The clinical picture of chronic pharyngitis is well defined but insufficiently clarified as to its morphological nature. In our study of 12 children with chronic pharyngitis who underwent adeno-tonsillectomies small pieces of tissue of the posterior wall of the pharynx were microscopically examined. In most instances inflammatory infiltrations were absent. Present was a variably developed hyperplasia of the lymphatic tissues. In the more pronounced hyperplasias there was a lymphoepithelial disintegration that could account for the clinical manifestations and that perhaps could also be considered as a disposing factor for a bona fide pharyngitis. The micromorphological changes were divided into 4 stages.

A boy developed a nephrotic syndrome at the age of two years, and remained steroid sensitive for twelve years. In this time more than twenty relapses occurred. Two renal biopsies showed minimal changes. Renal function was normal all along. At an age of 14 years he developed an irreversible renal failure. Since this time he remained dependent to dialysis. A third renal biopsy now shows a perimembranous glomerulonephritis with a diffuse interstitial fibrosis.

The cytoplasmic uptake of3H-l-leucine and3H-l-proline by hepatocytes and cells of the proximal and distal convoluted and of the collecting tubules of the kidney was compared with that of3H-dl-leucine and3H-dl-proline in an autoradiographic study. 34 male white Sprague-Dawley rats were killed 1, 2, 6, and 24 hours after the intraperitoneal injection of these amino acids. The rate of incorporation of3H-l-leucine in the liver and in the renal tubules, as judged by the number of silver grains counted, was about twice that of3H-l-proline. In the tubules of the kidney the intensity of labelling progressively declined from the proximal convoluted to the collecting tubules. When the two3H-dl-amino acids were used, almost identical rates of incorporation were found in the liver as well as in the kidney. The only exception was the pars recta of the proximal tubule: Here there could be found an unusually high uptake of3H-dl-proline. The values were not only higher than those found for the uptake of3 dl-leucine in this particular segment, but they also surpassed those due to3H-dl-proline and3 dl-leucine in the other parts of the renal tubules, as well as in the liver. The conspicuously high labelling seen in the pars recta after the injection of3H-dl-proline suggests that there is present in the cells of this segment ad-amino acid oxidase, which may be relatively specific ford-proline. The possibility is considered that this enzyme may participate in a detoxifying function of the pars recta.

The light- and electron microscopic changes in the glomeruli of the rat's kidney have been investigated in the course of ageing and after subtotal nephrectomy, constriction of the renal vein, and intoxication by N-nitrosomorpholine. In spite of the fact that four different experimental models have been used, identical changes were always found in the glomeruli. Morphologically they consisted of a diffuse thickening of the glomerular basement membrane and of an increase in the mesangial matrix without a proliferation of the glomerular cells. Despite this thickening of the glomerular basement membrane, functionally an increased permeability of the glomerular capillaries for macroproteins could be observed, shown by a moderate proteinuria. For these morphological changes the term "glomerulosclerosis" is suggested; they are interpreted as a non-specific, non-inflammatory reaction of the glomerulus to an impairment caused by a number of varied influences. From the study of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that in the individual experimental models the same result has been achieved in different ways. One possibility in the development of glomerulosclerosis is an increased production of the components of the basement membrane and of the mesangial matrix. This is the pathway which appears to be followed after nephrectomy. Another possibility is a slowing down of the breakdown of both the matrix and the membrane. This seems to be the case in the glomerulosclerosis occuring in the course of ageing, and after hypoxic and toxic changes. It could be accounted for by a functional disturbance of, presumably, the mesangial cells responsible for the breakdown of the basement membrane and of the matrix. On the other hand, one may have to consider a primary alteration of the macromolecules of these structures, as is already known from studies of the, chemically closely related, collagen. The light- and electron microscopic studies of the normal and of the altered glomeruli have led to certain conclusions concerning the origin and the fomation of the glomerular basement membrane and the mesangial matrix. In order to widen the scope of the studies, additional autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin and semithin sections of the rat's glomeruli. The results of the studies presented here suggest that of the three cell types of the glomerulus the visceral epithelial cells (podocytes, "Deckzellen") may participate on the formation of the glomerular basement membrane, whereas the mesangial cells appear to be responsible for the synthesis of the mesangial matrix.

The connective tissue of a lethal EDS IV case was investigated for the reasons of the manifested disturbances of the arterial wall. This functional disorder was attributed to the mechanical decoupling of elastin and collagen, with the premise of a composite material consisting of cellular, fibrillar, lamellar and other matrix components. A conceivable relation between the manifested deficiency of type III collagen and a disturbed anchoring of elastin is shown. These findings are supported by biochemical, morphological, x-ray and mechanical data.

Der Versuch, die Aorta durch ein freies autologes Darmtransplantat zu ersetzen, war von mehreren Arbeitsgruppen mehr oder weniger erfolgreich unternommen worden (1, 2, 3, 5). Nachdem SCHMIDT und BRUCH die Prinzipien fur eine freie Transplantation glatter Muskulatur unter der Voraussetzung der physiologischen Vordehnung erarbeitet hatten (4), wurde versucht, den Dunndarm als Aortenersatz zu verwenden. Zielsetzung der Versuchsreihe sollte es sein, die physiologischen Bedingungen beim Einbau des Transplantates zu ergrunden und die dabei auftretenden morphologischen Veranderungen der Gewebsstruktur zu beobachten.

The diabetic glomerulosclerosis as a consequence of the abnormal metabolic state is characterized by an uniform thickening of the glomerular basement membrane (GBM) and an augmentation of the mesangial matrix. Both alterations begin already few years after the onset of the diabetes and are observed in all glomeruli to the same extent (=diffuse type). Later on, nodular deposits of glycoproteins are additionally found in the mesangium (=nodular type). Only these nodules are morphologically specific for the diabetic disorder. In association with both the diffuse and the nodular glomerulosclerosis, insudation of plasma can be seen in the afferent and efferent vessels and the glomerular capillary loops. The mechanism of the increase in the amount of GBM-material is not known, since contradictory data have been reported with regards to both the chemical composition and metabolism of the GBM in human and experimental diabetes. Some postulate that the abnormal deposition of GBM-mateiral is due to an excessive synthesis (anabolic disorder), others argue that a further decrease in the normally slow breakdown and disposal (catabolic disorder) might be responsible. This review presents the different pathogenetic concepts of the glomerulosclerosis and attemps to explain the possible causes for the current discrepancies.

To study the origin and the formation of the glomerular basement membrane, autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin with semithin sections of the glomeruli of 42 male rats. The results of this study indicate that, of the three cell types of the glomerulus, the epithelial cells (=podocytes) synthesize the proline-rich scleroproteins of the glomerular basement membrane. Our autoradiographic studies have yielded no evidence for participation of the endothelial or mesangial cells in the formation of the basement membrane. The mesangial cells appear to be responsible for the synthesis of the mesangial matrix only.

The course of illness of a male infant who lived for seven months with a diffuse, nesidioblastic hyperplasia of pancreatic islets is described. Before surgical intervention the diagnosis should be ascertained by 1. observation of acetonuria which is always absent after hypoglycemic episodes, 2, the typical constellation of insulin concentration, free fatty acid concentration and beta-hydroxybutyrat during a hypoglycemia (as found by Baker et al. 1976) and/or by simultaneous measuring of glucose-insulin levels under the conditions of fasting as well as of oral leucine, oral glucose and intravenous tolbutamide loading. Therapy with diazoxide should be tried in any case. If all conservative measure fail and relative or absolute hyperinsulinemia is proved, experience shows that an immediate operation is indicated.