[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.

Leukotriene synthesis by human gastrointestinal tissues.

The prostaglandin and leukotriene synthesizing capacity of human gastrointestinal tissues obtained at surgery was investigated using radioimmunoassay for prostaglandin E2, leukotriene B4 and sulfidopeptide leukotrienes. The leukotriene immunoassay data were validated by high-pressure liquid chromatography (HPLC). During incubation at 37 degrees C, fragments of human gastric, jejuno-ileal and colonic mucosa released considerably larger amounts of prostaglandin E2 than of leukotriene B4 and sulfidopeptide leukotrienes. Gastrointestinal smooth muscle tissues released even larger amounts of prostaglandin E2, but smaller amounts of leukotrienes than the corresponding mucosal tissues. Adenocarcinoma tissue released larger amounts of leukotriene B4, sulfidopeptide leukotrienes and prostaglandin E2 than normal colonic mucosa. Ionophore A23187 (5 micrograms/ml) did not stimulate release of prostaglandin E2 from any of the tissues investigated, but enhanced release of leukotriene B4 and sulfidopeptide leukotrienes. HPLC analysis demonstrated that immunoreactive leukotriene B4 co-chromatographed almost exclusively with standard leukotriene B4, while immunoreactive sulfidopeptide leukotrienes consisted of a mixture of leukotrienes C4, D4 and E4. Leukotriene synthesis by human gastrointestinal tissues was inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual enzyme inhibitor BW755C (3-amino-1-(trifluoromethylphenyl)-2-pyrazoline hydrochloride). Synthesis of prostaglandin E2 was inhibited by the cyclooxygenase inhibitor indomethacin as well as by BW755C. Incubation of gastrointestinal tissues in the presence of glutathione decreased the amounts of leukotrienes D4 and E4, while release of leukotriene C4 was simultaneously increased. On the other hand, incubation of tritiated leukotriene C4 with incubation media from human gastric or colonic mucosa resulted in conversion of the substrate to [3H]leukotriene D4 and [3H]leukotriene E4. The results indicate the capacity of human gastrointestinal tissues to synthesize the 5-lipoxygenase-derived products of arachidonate metabolism, leukotriene B4 and sulfidopeptide leukotrienes, in addition to larger amounts of prostaglandin E2. Furthermore, considerable activities of the sulfidopeptide leukotriene-metabolizing enzymes gamma-glutamyl transpeptidase and dipeptidase were detected in human gastrointestinal tissues. These enzymes might play an important role in biological inactivation and/or change of biological profile of sulfidopeptide leukotrienes generated in the human gastrointestinal tract.

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 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.

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.

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.

Morphology and pathogenesis of pneumoconiosis in dental technicians.

The morphology of pneumoconiosis occurring in dental technicians could be studied by systematic light and electron microscopical investigation of 30 lung preparations from such cases. Diffuse streaky fibrosis and, in some cases, nodular fibrosis was observed together with occasional formation of silicotic nodules that may lead to extensive transformation of the alveolar structure. The etiological relationship between occupational dust exposure and pulmonary changes could be documented by element analysis of dust deposits on histologic sections, and of dusts from grinding and polishing instruments collected in the laboratory. The energy-dispersive X-ray microanalysis used in this study helps to differentiate and delimit this form of pneumoconiosis. The pathogenesis is discussed on the basis of light and electron microscopic results and physicochemical analyses.

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.

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.

[Leukotriene synthesis by gastrointestinal tissue and its pharmacologic modification]. / Leukotriensynthese durch gastrointestinales Gewebe und ihre pharmakologische Beeinflussung.

Tissues of the gastrointestinal tract synthesize leukotriene (LT) B4 and the sulfidopeptide-leukotrienes LTC4, LTD4 and LTE4 from endogenous substrate. Formation of leukotrienes was demonstrated using radioimmunoassay, high pressure liquid chromatography (HPLC) and bioassay. Under basal conditions the gastrointestinal tissues released minor amounts of leukotrienes only. Formation of lipoxygenase-derived products of arachidonic acid metabolism was, however, significantly increased in the presence of various stimuli. Thus, significant amounts of LTB4 and of sulfidopeptide-leukotrienes were released from colonic and gastric mucosa of guinea-pigs sensitized against ovalbumin when incubations were carried out in the presence of antigen. Antigen-induced leukotriene formation was not found in the muscularis propria and subserosal of ovalbumin-sensitized guinea-pigs. Release of cyclooxygenase-derived metabolites of arachidonic acid, on the other hand, was most abundant in the subserosal layer of the guinea-pig colon and was not influenced by the immunological reaction. Inhibitors of cyclooxygenase, such as indomethacin, reduced gastrointestinal formation of prostaglandins, but not of leukotrienes. Inhibitors of 5-lipoxygenase, however, significantly decreased leukotriene formation. Synthesis of LTB4 and of sulfidopeptide-leukotrienes was also found in human colonic mucosal tissue, using the divalent cation-ionophore A23187 as stimulating agent. HPLC analysis demonstrated that the sulfidopeptide-leukotrienes released were composed of a mixture of LTC4, LTD4 and LTE4. In addition, human colonic mucosal tissue contained high activities of enzymes that rapidly convert LTC4 to LTE4. As in most biological systems LTE4 is less active than LTC4 and LTD4 degrading enzymes might represent a local inactivating mechanism. Mucosal tissue of patients with Crohn's disease synthesized considerably more LTB4 and sulfidopeptide-leukotrienes than non-inflamed mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphology of the bronchial lining layer and its alteration in IRDS, ARDS and COLD.

Both light and electronmicroscopic examinations of the collocation of surfactant secreted by the alveoli into the bronchi were performed on material obtained from biopsies and autopsies. In the sol phase and especially along the border between the sol and gel phases of the bronchial mucus layers regularly arranged, partially stretched and partially reticulated osmiophilic membranes could be demonstrated. Their detailed structure corresponds with the structure of the phospholipid membranes of the surfactant in the alveoli. The functional significance of this surfactant portion for bronchial clearance is discussed in relation to the changes in structure of these membranous bodies, and their collocation in the mucus layers in chronic bronchitis, ARDS and IRDS.

[Determination of organic elements in histological sections (author's transl)]. / Elementaranalyse am histologischen Schnitt.

In the microscopic differential diagnosis of fibrosing lung processes organic deposits are often encountered which defy identification by histological methods. Assessment of the aetiological significance of these deposits depends on an accurate analysis. Energy-dispersive X-ray microanalysis with an electron microscope provides the means to identify organic deposits in the tissues. Such analyses, which do not require elaborate techniques, show up the type and structure of the deposits and the topographical relation to the lung lesion. They provide detailed information for assessing pulmonary lesions caused by fibrosis-inducing dusts.

Morphological alterations to the bronchial mucosa in high-dosage long-term exposure to sulfur dioxide.

Light- and electron-microscopic studies were carried out on chronic bronchitis in the rat, produced by high-dosage long-term exposure to sulfur dioxide. Particular attention was given to the advanced stages of the disease. Inflammatory intramural infiltration and fibrosis developed in the regions of the bronchial tree near the hilus and in the peripheral sections. The highly differentiated cells of the bronchial epithelium perish at the same time. After a loss of the goblet and ciliate cells, extensive epithelial metaplasias with dysplasias develop in the central regions of the bronchus. Bronchiolitis obliterans develops in the peripheral regions of the bronchus. In the bronchiolar epithelium, the Clara cells, which play a crucial role in the maintenance of bronchial secretion in the advanced stages of the disease, are preserved.

[The morphology of bronchial clearance]. / Morphologie der bronchialen Clearance.

The secretion of bronchiolar and bronchial epithelium was investigated in human biopsy material by electron microscopy. The secretion of Clara cells in the bronchioli of the goblet cells of bronchial epithelium and the secretion of peribronchial glands produce the gel phase of mucus above the bronchial mucosa. This gel phase is transported on the periciliary sol phase through the cilia beat, which consists of intercellular fluid. Foam-like, regularly arranged surfactant structures are detectable in this sol phase. Due to its surface-active qualities this surfactant, which is formed in the pneumocytes II of the alveolar system, has an anti-adhesive effect on the border between the sol and gel phase of the mucus. Furthermore, it contributes to the stabilisation of the water content in the sol phase, which is of decisive importance for the ciliary mucus transport. The morphological results agree with the results from the physiological and biochemical investigations, indicating that the surfactant has an important function in bronchiolar and bronchial clearance.

[Transmission and scanning electron microscopic investigation of the structure of so-called Clara cells of the bronchial system]. / Transmissions- und rasterelektronenmikroskopische Untersuchungen zurStruktur der "Clarazellen" des Bronchialsystems.

The epithelium of the bronchi and bronchioles were systematically examined in the lungs of rabbits. Particular attention was paid to the morphology of the Clara cells in the secretory phases. The apocrine secretion of these cells could be reconstructed from the results obtained. On the basis of morphological observations, the Clara cells produced a serous secretion which was mixed with the mucous secretion of the goblet cells in the bronchi. From these morphological results, the effect of substances which break down the secretion and also the morphological relationship of the Clara cells gain special interest.

Morphological features of the interaction between mucus and surfactant on the bronchial mucosa.

The secretion layer over the bronchial epithelium was investigated on human biopsy material. In the sol phase of the secretion, phospholipid membranes stretched out or arranged in vesicular structures could regularly be demonstrated. They displayed the same structure as the surfactant material in the alveolar space. It can be inferred therefrom that the surfactant is excreted via the bronchial system. It probably contributes to the stabilization of the sol phase of the mucus and thus influences the sliding capacity of the gel phase. So the surfactant has an important function in maintaining mucociliary clearance at the bronchial mucosa.