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Biomedical subjects

J Bruch

Publications and source records attributed to J Bruch.

At least 55 records · Page 3Linked to original sources

ZOO-FISH analysis: cat and human karyotypes closely resemble the putative ancestral mammalian karyotype.

DNA in situ hybridization with human chromosome specific DNA libraries was applied to compare the karyotypes of humans (Homo sapiens, 2n = 46) and cats (Felis catus, 2n = 38). For the autosomes alone, 30 segments of conserved synteny were revealed. The arrangement of these segments in the feline karyotype differs by only seven single chromosome breaks and one intrachromosomal inversion from their arrangement in humans. Comparison of these data with those recently obtained for pig and those available from conventional gene mapping studies in mice and cattle has allowed us to develop a model of karyotype evolution in mammals. The cat and human karyotypes, with 36 and 44 autosomes respectively, were found to be very similar to a putative ancient mammalian founder karyotype. It would appear that during evolution to the human karyotype the status quo has been conserved for at least some 100-120 million years. There has been no need to alter the well-balanced gene arrangement of the mammalian founder karyotype.

Animals↗

Does lung contusion affect both the traumatized and the noninjured lung parenchyma? A morphological and morphometric study in the pig.

Isolated unilateral lung contusion (LC) was induced in 12 pigs to determine the pathophysiological role of LC in the high mortality after multiple injury. The Horovitz quotient, pulmonary vascular resistance, mean pulmonary artery pressure, mixed venous oxygen consumption, inspiratory pressure and compliance were significantly decreased in the LC group as compared to controls. The number of polymorphonuclear granulocytes, the microvascular permeability of albumine and the Wilhelmy balance as determined by bronchoalveolar lavage were significantly increased after lung contusion. As indicators of a systemic reaction we found elevated plasma levels of the terminal complement complex and decreased levels of the complement factor 3a after LC. The morphological assessment revealed changes such as those encountered during the early phase of adult respiratory distress syndrome, with granulocyte sticking, endothelial cell adhesion and transendothelial diapedesis. Morphometric analysis demonstrated a significant decrease in alveolar diameter in both the injured and the contralateral lung due to impaired surfactant surface activity. A distinct increase in septal diameter, related to edema and caused by increased microvascular permeability, was found in the injured lungs. These findings emphasize that LC leads to a generalized impairment of the entire lung, which may lead to progressive lung failure.

Albumins↗

Chromosomal assignment of seventeen porcine microsatellites and genes by use of a somatic cell hybrid mapping panel.

Swine-specific sequence tagged (microsatellite) sites, STS and STMS, were assigned chromosomally by polymerase chain reaction analysis of a somatic cell hybrid panel. This study confirms the localization from genetic mapping of seven anonymous microsatellites and the genes ANPEP, ATP2, CGA, DAGK, FSHB, IFNG, IGF1, IL1B and SPP1. New assignment for the gene BNP1 to chromosome 6 is reported. The confirmed and the new assignments extend the information of the previously established linkage maps and provide framework loci on which to order additional informative markers.

Animals↗

Morphometry of experimental lung contusion: an improved quantitative method.

Alterations of lung tissue following pulmonary contusion are mainly assessed qualitatively. Quantitative examinations were limited up to now, to investigations in X-ray and computer tomography images, since morphometry of contused and normal biotic lung tissues seemed to be methodologically unfeasible. In order to overcome this shortcoming, the lungs of pigs were examined after unilateral lung contusion. In semithin sections, the thickness distribution of the interstitium and the volume distribution of the alveolar cavities were studied. Using an image analysis system a sequence of detection, erosion and skeletonisation steps were used to recognize the septal tissue correctly. The percent distributions were calculated from chord measurements after a sequence of erosion steps. It turned out that this technically simple procedure enabled highly reliable and valid results to be obtained, concerning the morphometric analysis of the alterations in the contused, as well as in the non-injured lungs.

Animals↗

A simple and accurate method for 3-D measurements in microcorrosion casts illustrated with tumour vascularization.

Microvascular corrosion casting is an established method to investigate vascular patterns of nearly all organs. Trying to evaluate these specimens quantitatively using native scanning electron microscope (SEM) pictures always implied a big error, because the information of depth cannot be taken into account. However, SEM stereo pairs allow for exact measurements. Tumour microcorrosion casts were used to demonstrate the feasibility of this 3-D quantification method. The information of depth was calculated for each measuring point using the parallax. From the resulting coordinates the intervascular distances, the interbranching distances as well as the interbranching angles were determined. We found significant differences between all investigated tumours. Reproducibility tests and tests for the greatest error possibilities resulted in a maximum deviation of 2.5% to be expected. Consequently this method is suitable for all application ranges of microvascular corrosion casting as a quantitative determination method.

Animals↗

Association of increased bronchoalveolar lavage fluid albumin and serum beta 2-microglobulin with pulmonary complications after allogeneic bone marrow transplantation.

The aim of this prospective study was to identify markers in bronchoalveolar lavage fluid (BAL fluid) and serum predictive for the development of pulmonary complications in the early phase (< 50 days) post-BMT. Concentrations of BAL fluid albumin (alb) and serum beta 2-microglobulin (S-beta 2m,) were determined 10 days before BMT (BAL-B, baseline) and on day 1 post-BMT (BAL-1) in 20 patients who subsequently developed pulmonary complications (group 1) and in 66 patients who remained free of complications for a minimum of 12 months (group 2). Median BAL fluid alb concentrations were significantly (P < 0.05) higher in group 1 patients as compared to group 2 patients at BAL-B (40 vs 28 mg/l) and at BAL-1 (30 vs 15 mg/l). S-beta 2m at BAL-1 was also significantly elevated in group 1 patients (median 1.3 mg/l) compared to group 2 patients (median 1.15 mg/l). Using cut-off values for BAL fluid alb (> 23 mg/l) and S-beta 2m (> 0.8 mg/l) we identified 12 patients out of 19 who developed subsequent pulmonary complications from 12 out of 62 patients without such complications, 1 day post-BMT.

Adolescent↗

Toxicological investigations on silicon carbide. 1. Inhalation studies.

The question of lung damage as a result of exposure to silicon carbide (SiC) was investigated by inhalation experiments to obtain information on the qualitative response of lung tissue to the test substance (SiC). For comparison, quartz, kaolinite, and tempered clay dusts were used. The indices for the effects of the dusts studied were organ weights, numbers of bronchoalveolar cells, lung surfactant phospholipid concentrations including subfractions, and lung clearance. Exposure to the test samples was carried out according to the Essen inhalation model in two independent series. The results of the two series were similar: Compared with sham controls, exposure to SiC did not affect the indices studied. Even at a low dose (a quarter of the SiC dose) quartz gave pronounced deviations in all indices. In particular, an increase in granulocytes indicated toxic properties of the dust. The long term elimination of quartz from the lung was worse than that of SiC. The kaolinite and tempered clay dusts were intermediate between SiC and quartz based on several of the indices studied. It is concluded that SiC is deposited practically inert in the lung.

Administration, Inhalation↗

Toxicological investigations on silicon carbide. 2. In vitro cell tests and long term injection tests.

Silicon carbide (SiC) dust and other dusts for comparison were injected intratracheally at a high dose (50 mg) into rats and the response of the lungs and the lymph nodes was studied after an appropriate experimental period. The indices studied were: histological changes in the lung and lymph nodes, organ weights, the formation of collagenous fibres, and the appearance of quartz typical areas. According to several epidemiological investigations and previous experimental animal studies, SiC produces silicogenic (fibrogenic) effects. No changes in the tissues studied in terms of damaging fibrogenic effects could be found after eight months (first series) and three and 12 months (second series). In particular, the histological findings and the absence of quartz typical areas as well as the quantitative determination of collagen fibres show that SiC had no harmful effects on tissues. Based on these results, the extent to which other exposures during the production of SiC can be responsible for the established radiological alterations is discussed. Without doubt the following may be confounders: SiC fibres, crystalline SiO2 (quartz, cristobalite, tridymite), and possibly gaslike emissions (SO2). From the hygienic medical point of view the workplaces during SiC manufacture should be examined carefully. The substance SiC dust as such can be considered as inert from the experimental results based on qualitative and extremely sensitive procedures. A revision of the present threshold value for SiC in ther German MAK list is called for.

Animals↗

[Repeated routine determination of pulmonary microvascular permeability after polytrauma].

We present a technique to measure pulmonary microvascular permeability for albumin in patients with multiple trauma by means of bronchoalveolar lavage (BAL). Routine laboratory tests for the analysis of BAL fluids are used. The results were clinically validated in 10 healthy volunteers and 12 patients with multiple trauma in a first prospective study. Additionally, another 11 severely traumatized and 24 less traumatized patients were evaluated in a second prospective study. Normal values (> 0.09 +/- 0.02), posttraumatic physiological ranges (< 0.35), and a "high risk" range (> 0.5) for pulmonary microvascular permeability for albumin were developed. There was a high correlation between the first posttraumatic values of pulmonary microvascular permeability and the required duration of intensive care treatment (r = 0.81), the duration of continuous mandatory ventilation (r = 0.78) and the mean lung injury score by Murray (r = 0.76). We conclude that the presented method is harmless and useful to describe the post-traumatic course of pulmonary microvascular permeability.

Adult↗

Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and activated conditions.

When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six times with physiological saline, approximately the same number of alveolar macrophages (AM) were found in the first and second BAL, whereas in the third fourth, fifth, and sixth BAL, the number of AM decreased exponentially. Morphometric counting of the number of AM in histological sections of lung tissue showed that only 14% of the AM population had been recovered by BAL. Although additives to the BAL fluid such as lidocaine and/or fetal calf serum increased the AM count in the first washing considerably, the total number of AM washed out remained unaltered. Addition of the phagocytosis stimulant zymosan increased the AM count in BAL by a factor of more than 2. On stimulation of the lungs with an inert dust (silicon carbide), the AM count in the BAL and the lung was only slightly increased 8 weeks after intratracheal instillation. In contrast, after exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was significantly increased, and the recovery of AM had also increased by a factor of approximately 2. The experiments show that it is the micromilieu of the alveoli and the condition of the AM (certain physiological activation states, such as phagocytic activity) that essentially determine the degree of recovery.

Animals↗

Activity testing of alveolar macrophages and changes in surfactant phospholipids after irradiation in bronchoalveolar lavage: experimental and clinical data.

This study presents results of bronchoalveolar lavage (BAL) after irradiation to the lungs in mice as well as clinical data. The number of BAL cells, mainly macrophages, lymphocytes, and granulocytes, changed in a time-dependent manner. The phagocytic activity of the macrophages measured as the phagocytosis of microbeads and measured as the esterase activity also showed a strong time-dependent increase during the acute phase up to 21 days after irradiation. The contents of surfactant phospholipids (SF) and sphingomyelin (SPH; as a parameter for cell death) were quantified by HPLC. Both were significantly changed between day 2 and 21 after irradiation. Three BALs of a patient with idiopathic interstitial pneumonitis, who had received an allogenic bone marrow graft after total body irradiation with 10 Gy, showed similar effects in the cellular and surfactant parameters. These data indicate that there are positive interactions between the number of different BAL cells, macrophage activity, and SF and SPH content in the preclinical model of the mouse as well as in the clinical situation after lung irradiation.

Animals↗

Radiation-induced changes in lung tissue and development of fibrosis determined by quantitative morphometric methods.

This study presents results of morphometric investigations of mouse lungs after single irradiation. An automatic image analyser was used to monitor pathological changes in morphological structure, especially the size and distribution of collagen fibres, the thickness of the septa and the diameters of alveoli in the lung. Radiation-induced changes in the area of alveoli and septa as well as collagen content were seen 11 weeks after irradiation. A dose-dependent increase in tissue and decrease in alveolar surface as well as a quantifiable increase in radiation oedema were seen. The septa were thickened and the total collagen content increased in a dose-dependent manner. The morphometric methods used here are suitable for determining changes in lung structure, particularly those in collagen content in the early phase of a pathological response after thorax or total body irradiation for conditioning in bone marrow transplantation.

Animals↗

Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure.

Pulmonary surfactant, which is crucial for alveolar stability, may also be involved in endogenous defense mechanisms of the lungs. Thus, alterations in pulmonary surfactant may promote infections, including pneumonia and septicemia. Because patients who have acute respiratory failure often develop pneumonia, thus septicemia, we investigated when surfactant is altered in these patients and whether there is a specific pattern of changes in surfactant phospholipid composition associated with septicemia in these patients. To answer these questions, we determined the phospholipid content and composition in lung washings obtained from alveolar sites (by bronchoalveolar lavage) and from tracheal sites (by aspiration). Both techniques were performed serially over a period of 18 days in 30 patients who had acute respiratory failure resulting from polytrauma, 18 of whom developed septicemia caused by pneumonia. We found that in lung washings obtained from the alveolar sites from all patients, the phosphatidylglycerol content was decreased and the phosphatidylinositol content was increased as early as 6 hr after trauma and normalized during recovery of the patients. In addition, alveolar phosphatidylcholine content was decreased 24 hr after trauma. In patients who developed septicemia during the observation time, but not in patients who had uncomplicated courses of acute respiratory failure, the concentrations of alveolar phosphatidylethanolamine (normally 4.8% of total phospholipids) and alveolar phosphatidylcholine (normally 62.8%) both approached the proportions found in the trachea (phosphatidylethanolamine 33.4%, phosphatidylcholine 35.6%), suggesting that surfactant phospholipid pool size had progressively decreased. Our results indicate that in patients who have acute respiratory failure, pulmonary surfactant is altered very early, and that when septicemia complicates the course of acute respiratory failure, the surfactant phospholipid pool size decreases progressively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Distribution and function of alveolar cells in multiply injured patients with trauma-induced ARDS.

To determine whether alveolar cells are involved in the pathogenesis of adult respiratory distress syndrome (ARDS), we assessed the distribution and function of alveolar cells from 30 polytraumatized patients with trauma-induced respiratory failure, 5 of whom also had lung contusion. Cells were obtained by bronchoalveolar lavage performed daily beginning on the day of trauma and continuing for 14 days. Neutrophils constituted about 60% of lavage cells in ARDS patients with lung contusion 0-2 days after polytrauma and about 50% in ARDS patients without lung contusion. In ARDS patients with lung contusion the neutrophil fraction decreased to 52% 3-6 days after trauma and to 40% 7-14 days after trauma. In patients without lung contusion the neutrophil fraction increased to 77% and then decreased to 60% at these times. Total cell counts in ARDS patients with lung contusion were more than twice as high as in patients without lung contusion 0-2 days after trauma. The difference in total cell counts decreased during days 3-6 and disappeared by day 7. In all patients morphologically altered alveolar cells were observed 4 days and more after trauma. In non-survivors significantly more altered cells were found. The chemiluminescence-response pattern of the alveolar cells was enhanced throughout the study and correlated with the neutrophil fraction (r = 0.6). The neutrophil fraction also correlated with the pulmonary vascular resistance during the first two days after trauma (r = 0.53). We conclude that alveolar cells are involved in the pathogenesis of trauma-induced ARDS and that the alveolar cell distribution is different in patients with and without lung contusion during the development of posttraumatic respiratory failure.

Acute Disease↗

Pulmonary changes in the rat following low phosgene exposure.

Minimal inhalation doses (or concentrations) of phosgene necessary for the production of changes within the blood-air barrier were determined in rats. At least 50 ppm.min (5 ppm X 10 min) was necessary for the production of alveolar oedema (the minimal effective phosgene concentration being 5 ppm). While the smallest phosgene dose to produce an increase in pulmonary lavage protein content was also 50 ppm.min and while the smallest phosgene dose to produce widening of pulmonary interstices was 25 ppm.min, there was no phosgene threshold concentration (down to 0.1 ppm) for these two latter parameters, which are assumed to be indicators of physiological compensatory mechanisms within the blood-air barrier. The primary localisation of pulmonary damage seemed to depend on the concentration of phosgene used: at low concentrations (0.1-2.5 ppm) the changes were primarily located at the transition from terminal bronchioles to the alveolar ducts; at higher concentrations (5 ppm) damage to the alveolar pneumocytes (type I) was more conspicuous.

Animals↗