[Odontogenic cysts]. / Odontogene Kieferzysten.

Odontogenic cysts form a group of diseases whose origin is linked to the persistence of epithelium resulting from the complex embryonic development of the teeth and jaws within the connective tissue. Inflammatory reactions of the surrounding area of the persisting odontogenic epithelium accompany epithelium proliferation, which leads to the development of a gradually expanding cavity that supersedes the surrounding structure. The correlation between activity of the inflammatory reaction and the development of the epithelial proliferation results in a relatively broad variation of histological features of the cyst wall. Since classification of cyst forms depends on their topographical features, clinical information on the classification of variations is urgently needed. For the classification of their clinical course of development and, in particular, in order to differentiate them from cystic odontogenic tumors of the jaw region, a histological examination of cyst wall tissue is necessary, all the more so since the development of a carcinoma deriving from the odontogenic epithelium has only been described in very few cases.

[Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the renal parenchyma under aspirin use. Electron microscopic findings in the rat kidney]. / Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS). Elektronenmikroskopische Befunde an der Rattenniere.

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.

Ultrastructural changes in the cilia of experimental mice.

Mice lacking dynein arms in the cilia were examined; the strain was obtained by inactivation of dynein heavy chain gene in chromosome 7. The cilia of these mice were examined by electron microscopy and compared to the cilia of random-bred mice. No statistically significant differences or typical disorders in the outer or inner dynein arms were detected. The number of inner dynein arms was lower, in some cilia secondary changes presenting as swelling of the outer part of the ciliary membrane or formation of complex cilia were seen.

Infection of murine precision cut lung slices (PCLS) with respiratory syncytial virus (RSV) and chlamydophila pneumoniae using the Krumdieck technique.

The Krumdieck technique allows the investigation of the so-called precision cut lung slices (PCLS) with a special microtome. It is thus possible to evaluate morphologic changes over a longer period of time using only a small group of animals. Chlamydophila pneumoniae (Cp) and respiratory syncytial virus (RSV) proved to be important causes of pneumonia, rhinitis and exacerbations of asthma bronchiale, as well as of lower respiratory tract infections in young children. PCLS should be tested for their suitability as an in vitro model for these infections. The PCLS were infected with Cp and RSV over different periods of time. Investigations were carried out by light and transmission electron microscopy (TEM). Furthermore, immunofluorescence (IF) studies with antibodies against bacterial or viral proteins and cell-specific markers were done using confocal laser scanning microscopy (CLSM). Non-infected and infected PCLS showed a well-preserved morphology up to 72 hours. After short infection intervals, typical inclusions of Cp or RSV were detected in vacuoles of different cell types. Infection and cell types could be verified using IF. Cytopathic effects were not prominent. Ciliary beat was detectable up to 96 hours after infection. This in vitro technique offers the possibility of studying mechanisms and effects of bacterial and viral infections on viable tissue complexes.

[Aortic rupture in idiopathic Gsell-Erdheim medial necrosis]. / Aortenruptur bei idiopathischer Medianekrose Gsell-Erdheim.

HISTORY AND CLINICAL FINDINGS: A 75-year-old man was admitted with increasing dyspnoea and recurrent left-sided chest pain, at first during exercise and later at rest. No cardiovascular risk factors could be found. His past medical history revealed mastectomy and radiotherapy for breast cancer and an operation for benign prostate hyperplasia. At admission the patient was in very poor conditions with marked orthopnoea. Bilateral moist rales were heard over both lungs with a 3/6 diastolic murmur an cardiac auscultation. INVESTIGATIONS: Anterolateral ST segment depression in the ECG and signs of pulmonary oedema in chest X-ray were also noted. Echocardiography discovered global reduced left ventricular contractility with aortic insufficiency (II degree) in mild aortic valve sclerosis. Coronary angiography demonstrated marked dilatation of the coronary arteries without stenosis. The ascending aorta was dilated without angiographic signs of a dissection. DIAGNOSIS, TREATMENT AND COURSE: After medical treatment and a short period without symptoms the patient had to be resuscitated and died after a intense attack of dyspnoea and chest pain. The autopsy revealed a focal dissection of the ascending aorta with a small aortic rupture caused by idiopathic Erdheim's medial necrosis. CONCLUSION: Erdheim's medical necrosis is an important cause of aortic dissection and aortic rupture. If symptoms of acute severe chest pain are present and a coronary syndrome can be excluded, possible disease of the aorta should be investigated. The reported case demonstrates the short time window between onset of symptoms and the necessary treatment.

The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosis.

Chlamydia pneumoniae has been detected in atherosclerotic plaques by various means. Chlamydiae are able to cause persistent infections. Serologically elevated antibody titers are found in severe chronic obstructive pulmonary disease. In atherosclerosis and pulmonary emphysema, inflammatory reactions can be seen by means of light microscopy. Specimens from patients with obliterative arteriosclerosis undergoing thrombendarteriectomy and with advanced emphysema undergoing lung volume reduction surgery were examined using scanning (SEM) and transmission (TEM) electron microscopy, and using immunofluorescence with monoclonal antibodies and antiserum against chlamydiae. SEM shows spherical bodies (SBs) with a diameter from 0.3 microm to 0.6 microm on the surface of the alveoli and bronchioles, as well as in atherosclerotic plaques. In atherosclerosis and emphysema, SBs reveal a double membrane, adherence to collagen fibers, tissue destruction, as well as intracellular and interstitial localization in TEM. They show in parts a densely packed central structure. SBs are seen both in alpha-1-antitrypsin deficiency emphysema and smoker's emphysema. Using immunofluorescence microscopy, spots are seen in corresponding distributions to the SBs. Morphological findings are typical for aberrant chlamydiae seen in persistent infections. Chronic infection and bacterial colonization associated with progressive disease seems to be relevant not only in atherosclerosis but also in pulmonary emphysema.

Primary malignant fibrous histiocytoma of the lung: IGF-II producing tumor induces fasting hypoglycemia.

Augmented glucose utilisation or secretion of insulin-like-growth-factor II (IGF-II) are discussed as important pathogenetic factors in tumor-associated hypoglycemia (Doege-Potter Syndrome) with suppressed insulin and C-peptide levels. Primary malignant fibrous histiocytoma of the lung is an uncommon neoplasia and its association with hypoglycemia is rare and the causal relationship remains unclear. - We report a 57-year-old male with spontaneous hypoglycemia (1.67 mmol/l) due to a primary malignant fibrous histiocytoma of the lung, secreting IGF-II. Insulin (0.10 nmol/l; normal range 0.33-1.2) and C-peptide (3.0 mIU/l; 5-25) levels were suppressed in combination with low levels of growth hormone (<0.5 ng/ml; <7 ng/ml) and IGF-I (<66.0 ng/ml; 70-246). The elevated IGF-II level (787 ng/ml; 300-500) and decreased IGF-binding protein 3 (1.6 mg/l; 2-5) indicated a high free IGF-II activity. After surgery (resection of the right upper lobe), glucose (4.4 mmol/l), insulin (9.0 mIU/L) and C-peptide (0.84 nmol/l) levels returned to normal. Serum IGF-I (289 ng/ml) and the IGF-I/IGF-II ratio (<0.08 preoperative vs. 0.41 postoperative; >0.20) increased to the normal reference range. - In conclusion, malignant fibrous histiocytoma (MFH) is rarely described presenting as tumor-induced hypoglycemia. Doege-Potter Syndrome in MFH seems to be related to tumor-associated IGF-II production.

p53 mutations and codon 213 polymorphism of p53 in lung cancers of former uranium miners.

PURPOSE: There is a high prevalence of G-->T transversions of p53 in lung cancers of smokers. One study has reported a special "hotspot" mutation at codon 249 of p53 in lung cancers of former uranium miners. The aim of our study was to look for mutational spectra of p53 in former German uranium miners with lung cancers. METHODS: We investigated 16 patients with lung cancer who had worked as uranium miners in Germany and 13 lung cancer patients without a mining history of the same region. By means of the polymerase chain reaction and sequencing we looked for mutations in exons 5 7 of the p53 gene. RESULTS: We could not find any suggestion of hotspot mutations. The only G-->T mutation in former uranium miners was detected in the only nonsmoker. In 3 patients (19% of the total) we found a codon 213/3 polymorphism. CONCLUSIONS: The results indicate that G-->T transversions do not seem to be very common mutations in p53 in lung cancers probably caused by radiation. Therefore, p53 may be mutated early in lung cancer development if radiation exposure is a critical factor in carcinogenesis. In accordance with studies of thyroid cancer patients in the Chernobyl region, our results may indicate an overrepresentation of codon 213/3 polymorphism in p53 in radiation-caused cancers.

The role of persisting infections in the pathogenesis of pulmonary emphysema. Electron microscopy reveals a probable bacterial colonization of the alveolar space and the bronchioles.

Lung volume reduction surgery (LVRS) yields resection specimens from patients with advanced pulmonary emphysema. Regarding the development of lung function parameters, recent results obtained by light microscopy revealed an unfavorable prognosis in patients with remarkable inflammation, particularly in the bronchioli. Tissue from ten patients (alpha1-antitrypsin level in the normal range) was furthermore investigated by electron microscopy. Scanning electron microscopy shows 0.4-0.6 micron spherical bodies variably densely arranged in the whole alveolar space and in the bronchioles of all patients. These bodies are mostly seen on the microvilli of type II pneumocytes. An immunological reaction with activation of macrophages and granulocytes occurs simultaneously. Macrophages show cytoplasmic extensions to the spherical bodies, which exhibit a cellular membrane but no cellular wall. This favors the diagnosis of bacterial colonization of the alveolar space and the bronchioles by mycoplasmas or L-forms of other bacteria. As patients undergoing lung volume reduction surgery are under optimal medical treatment and without any infection clinically, these findings appear to be relevant for the pathogenesis and/or progression of pulmonary emphysema.

Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney.

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Ischemia/reperfusion injury of the pancreas: a new animal model.

BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

[Pathologic-anatomic findings in surgical lung volume reduction of advanced emphysema]. / Pathologisch-anatomische Befunde bei der chirurgischen Lungenvolumenreduktion des fortgeschrittenen Emphysems.

Surgical lung volume reduction is a method for treatment of advanced pulmonary emphysema after all other therapeutic approaches have failed. 280 atypical lung resection specimen of 81 patients were examined pathologico-anatomically using routine stains. In all cases combinations of various forms of emphysema were found; in 65.8% there were also bullous changes (with > or = 1 cm diameter) focally. Acute bronchiolitis was seen in 41.8% of the specimens, an only slight (if at all) chronic bronchiolitis in 26.7% and bronchioloectasia in 45.4% of the cases. Focal intraalveolar aggregates of granulocytes were identified in 16.1%, and the process of permanent scarring resulting in "organised pneumonia" in 20.6% of the specimens. Occult neoplasms were found in 9.9% of the patients and specific changes in 27.2%. Bronchiolitis is relevant for postoperative prognosis and an indication for intensifying antibiotical and antiinflammatory therapy. Preoperative diagnostical procedures should be intensified to find out these patients. Inflammatory changes must be investigated in respect of etiology and pathogenesis.

Morphological studies of the respiratory syncytial virus induced bronchiolitis in experimentally infected calves.

RSV-infections of the lower respiratory tract in infancy and early childhood are the most frequent causes of a hyperreactive bronchial system and obstructive lung disease. Studies concerning the morphological alterations of the bronchial mucosa during an RSV-infection are dependent on an experimental animal model. In this study the alterations of the lower respiratory tract from five infected colostrum-fed calves during the initial stage of the infection are described. BRSV strain 375 was applied as an aerosol on four consecutive days. The animals showed clinical symptoms already on the first day after infection. 7 days after the first infection the calves were necropsied. Lobular distributed atelectasis of the lung were found. The corresponding bronchioli were collapsed. The bronchiolar lumina were filled with a putrid exudate. In the bronchiolar wall a band-like lymphocytic infiltrate was found. By confocal laserscanning microscopy and by scanning electron microscopy intracellular viral components marked by an antibody against the viral P-protein were depicted. The intracellular virus inclusions were arranged along the bundles of filaments of the cytoskeleton. By transmission electron microscopy an alteration of the ciliogenesis and in cases of severe cell damage, cell death could be observed. The morphological findings suggest that the cytoskeleton plays an important role in the development of bronchiolitis.

A model for respiratory syncytial virus (RSV) infection based on experimental aerosol exposure with bovine RSV in calves.

Five conventionally kept calves aged between 17 and 24 days were experimentally infected with bovine respiratory syncytial virus (BRSV) by aerosol in order to mimic the natural infection route. The calves were killed and autopsies performed 7 days after the first virus challenge. The BRSV isolate used induced tracheitis, bronchitis and atelectasis in infected calves. The only virus which could be isolated from the lungs of the calves was BRSV. In addition, Mycoplasma bovirhinis was isolated from the lungs or/and trachea of two calves. The clinical and histopathological findings, as well as the detection of BRSV antigens by immunofluorescence in the epithelial cells of lung and trachea, and the reisolation of the virus from bronchoalveolar lavage fluids of all inoculated calves, provided confirmation of successful infection with BRSV.

Morphological studies of graft pancreatitis following pancreas transplantation.

Morphological findings in the initial stages of graft pancreatitis were studied systematically in sequential biopsies of 16 human pancreatic allografts. In 14 patients clinical and morphological signs of graft pancreatitis developed in the early postoperative period. In all cases disturbances in the integrity of structures within acinar cells occurred during ischaemia. In ten cases activation of autophagocytosis occurred following reperfusion, with acceleration of cellular metabolism. After reperfusion a marked leucocyte reaction occurred with a later single acinar cell necrosis in six cases. At the same time, high serum pancreatic enzyme concentrations were observed in all patients following transplantation. Exocrine secretion from the allografts via the pancreatic duct was reduced, correlating with the severity of graft pancreatitis. Studies in this clinical situation might complement analyses of the cascade of morphological and pathophysiological reactions during the early stages of other types of acute pancreatitis.

Ultrastructural study on human lung in alveolitis versus pulmonary fibrosis.

Lung specimens of 21 patients with diffuse interstitial lung disease were examined. The present ultrastructural study outlines the topography and distribution of inflammatory changes in the interstitium, endothelium, and in pneumocytes and phagocytes. Alveolitis is characterized by marked regenerative activity of type II pneumocytes (cuboid metaplasia), intraluminal macrophage accumulation, endothelial swelling, multilamination of the endothelial basement membrane, pericapillary edema, and primarily by cellular infiltrates in the interstitial space. The most prominent feature of the interstitium in pulmonary fibrosis is the lack of immunoinflammatory cells. In some areas there is a marked absence of alveolar lumen while only a small number of macrophages are present in the remaining alveolar lumen. Most of the capillaries in the fibrous septum have been destroyed. Ultrastructural studies of lung biopsies in patients with diffuse interstitial lung disease allow the differentiation between alveolitis and pulmonary fibrosis and thus contribute to a therapeutic decision.

In vitro study of the bronchial mucosa during Pseudomonas aeruginosa infection.

The route of bacterial infection of the lower respiratory tract is generally one of descent subsequent to colonisation of the oral and oropharyngeal mucosa. The interaction between Pseudomonas aeruginosa (wild type) and the bronchial epithelium was studied in bronchial mucosal probes cultured in tissue culture medium. It was possible to demonstrate that, even after loss of the mucus layer, adherence between the bacteria and the bronchial epithelium does not take place if ciliary function remains intact. Only after mechanical destruction of the bronchial epithelium, in proximity to squamous metaplasia or after loss or malfunction of the cilia of the bronchial epithelial cells was adhesion between bacteria and bronchial epithelial cells or basement membrane demonstrated by electron microscopy. After loss of the cilia following adenovirus-infection, adhesion between P. aeruginosa and the bronchial epithelial cells was visible. These results indicate that ciliary function must be of crucial significance in bacterial epithelial colonisation.

The morphological substrate of autonomic regulation of the bronchial epithelium.

Observations of explanted bronchial mucosa show that ciliary function is maintained for 7 days subsequent to explanation. This finding demonstrates that non-neural mechanisms exist which regulate ciliary function. Ultrastructural and immunohistochemical studies both for light and electron microscopy were performed on human bronchial biopsy material and lung resection specimens in order to recognize the morphological substrate of this regulatory mechanism. A complex system of cytokeratin filaments and microtubules radiate through the whole cytoplasm of ciliated cells with direct contact to the nucleus, cilia, microvilli, desmosomes and to the apical terminal adhesive complex. Between the basal bodies and the apical terminal adhesive complex microfilaments can be found. In the apical cytoplasm a dense filamentary network is seen in association with the adhesive complex. These morphological findings indicate that the cytoskeleton of the bronchial epithelium plays a key role in the co-ordination of ciliary function.