Search

The hydroxylation of testosterone and 5alpha-dihydrotestosterone at C-2 was measured quantitatively in vivo and in vitro in rats by using "metabolically labile" tritium labelled substrates. The enzyme activity was dependent on the sex and age of the animals. There was a good correlation between in vivo and in vitro experiments. Whereas testosterone was hydroxylated only in liver, 5alpha-dihydrotestosterone was hydroxylated in adrenals, kidney, lung and prostate as well. Hydroxylation was not sex-dependent in adrenals and lungs.

The antibiotic concentrations were determined in 28 serum samples, 24 samples of lung parenchyma and 21 samples of the skeletal muscle from 28 patients who had undergone pneumonectomy. 5 g mezlocillin had been given i. v. as a bolus injection 30 to 150 minutes before sampling. The concentrations in the lung tissue were higher than the MICs for most bacteria for two hours. If a strain is less sensitive, a dose of more than 5 g is recommended. The concentrations in muscle tissue were also effective antibacterially.

A short review of different applications of enzyme-histochemistry and enzyme-cytochemistry in the field of lung pathology is given. As shown in own experiments, the phosphomolybdic-acid-stannous-chloride reaction (Landing et al. 1952) appears as a successful method for rapid demonstration of phospholipids in histological and cytological material. Application of histochemistry (reaction of acid phosphatase) in diagnostic of sarcoidosis (Kveim-test) gives in comparison with the traditional technique following advantages: 1. results are obtained more rapidly and with minor technical expense, 2. for pathologists, it is easier to differentiate between specific and non-specific reactions. With cytochemical methods (reaction of alkaline phosphatase) is is relatively easy to detect tumour cells in pleural fluids and ascites. This test (Eckert 1978, 1979) is neither cancer-specific nor does it cover all tumours cases. But its high positivity and its easy readability enable the technique to be used as a search method for tumour cells.

The influence of chronic administration of ambroxol on the phospholipid-(PL-) content and ultrastructure of lungs has been studied and compared with the effect of chlorphentermine (chlph.). Both drugs are amphiphilic substances. The causative factor of the well-known chlph. induced phospholipidosis-like alterations was suggested to be an inhibition of enzymatic degradation of PL. Rats were intraperitoneally treated five times per week for two weeks with chlph. (0,2 mMol per kg b.w.) and ambroxol (0.2 mMol per kg b.w.), respectively. Lung, heart, liver, kidney and spleen were light microscopically examined, and the lung was studied by electron microscopy. Furthermore, the PL-content of the whole lung tissue, the proportion of phosphatidylcholine (PC), the lung weight/body weight ratio (LM/KM) as well as the dry weight/wet weight ratio (TM/FM) of the lung was calculated. The application of chlph, induced an excessive PL-storage in the lung as indicated by an increase of the PL-content, of the PC-proportion as well as of the LM/KM and TM/FM ratio. The accumulated PL are detectable by electron microscopy, mainly in the lysosomes of macrophages appearing as lamellar or crystalloid inclusions. On the contrary, chronic application of ambroxol does not cause any substantial changes especially no abnormal lysosomal PL-inclusions. Therefore, it is suggested that ambroxol does not interfere with the PL-metabolism in a way comparable to that of the chlph. action.

It was examined, whether by intraamnial applicated lecithine an approaching respiratory distress syndrome could be prevented. This possibility of therapy was tested on a fetus unviable of life. It was shown by examining the lavage-fluid of the fetal lung, as well as the organ homogenates of lung; liver and gut, that the intraamnial applicated lecithine was metabolised and resynthesised in the organism. In the lung the lecithine was present as a complete molecule.

The fraction of crude glycosaminoglycans was prepared from an emphysematous lung by means of proteolytic digestion, precipitation with ethanol and fractionation with CPC (cetylpyridinium chloride). The above fraction of crude glycosaminoglycans was then subjected to chromatography with a column of Dowex-1. Individual glycosaminoglycan species was identified based on the results of electrophoresis and on those of incubation with specific mucopolysaccharide-lyases. As a result, hyaluronic acid, chondroitin sulfate A (C), dermatan sulfate and heparan sulfate were detected. Quantitation of individual glycosaminoglycan species revealed that the ratio to total glycosaminoglycan of hyaluronic acid was smaller in the emphysematous than in the normal lung. The significance which can be attributed to the change in quantity of glycosaminoglycan of the lung was discussed in relation to pathogenesis of pulmonary emphysema.

Extravascular lung water (EVLW) was determined with the thermal-dye double-indicator method (119 individual measurements) in 23 patients in an intensive-care unit, and the results were compared with estimates made from largely standardized portable chest X-ray films, using the staging method of Sibbald as well as that of Halperin. There was a significant correlation with the measured EVLW for both methods. Radiologically "normal" films corresponded to a mean EVLW value of 8.4 ml/kg body-weight. Radiologically judged adjacent stages did not in all cases compare with corresponding measured EVLW values. But when EVLW values were clearly abnormal, the X-ray films always demonstrated massive interstitial or alveolar infiltrations. Measurement of EVLW enables one accurately to judge the fluid contents of the lung and is superior to the assessment of the chest X-ray film.

Extravascular lung water is estimated in vivo from indicator dilution curves of diffusible and non-diffusible tracers utilizing their different transit times as they pass the lung microvessels. 131I-antipyrine as the diffusible and 99mTc-HSA as the non-diffusible tracer were injected simultaneously, using a pneumatic injector. Indices for rELW/V and rELW/F were calculated using programs previously published, and gave numerical values for the presence and intensity of pulmonary interstitial oedema. Inaccuracies due to sequential inputs are avoided. 131I-antipyrine has a more convenient pulmonary interstitial oedema. Inaccuracies due to sequential inputs are avoided. 131I-antipyrine has a more convenient shelflife and can therefore serve for emergency and follow-up examinations. The results do not differ significantly form those with 123I-antipyrine, and the higher radiation burden is tolerable. A mobile set-up for bed-side measurements is described.

Inhalation of man-made mineral fibers (MMMF) was performed with mini-pigs and beagles to examine the value of bronchoalveolar lavage for the detection of these fibers in the lung. The preparation of the BAL-fluid without filtration lead to the detection of a plentiful quantity of MMMF. With our investigations we could verify that in the final product mineral-wool a great spectrum of different seized fibers down to particles reaching the alveoli is present.

From investigations on microautoradiographs of suitable biological structures, it is concluded, that for the determination of photometric quantities without loss of accuracy a photometric resolution of n = 10 intervals of optical density is sufficient. A low photometric resolution allows to represent the local distribution of substances more clear and the expense of analysis is reduced.

Nickel and chromium analyses were performed in lung and kidney as well as in blood and urine samples of 45 autopsies from northern Bavaria area. The analyses were carried out with electrothermal atomic absorption after wet oxidative digestion. Median metal concentrations in blood were 4.5 micrograms Ni/kg resp. 2.8 micrograms Cr/kg, in urine 2.7 micrograms Ni/kg resp. 4.9 micrograms Cr/kg. The calculated values agree with the metal levels given in the new literature. Median metal concentrations in lung tissue were 7.4 micrograms Ni/kg resp. 36.5 micrograms Cr/kg; in the kidneys medians of 13.9 micrograms Ni/kg resp. 9.6 micrograms Cr/kg are found. In the literature only a few values for comparison are given. The metal concentrations in the different samples were not influenced by age or sex.

Measurements in ambient air have indicated, that air pollution contains fibrous dusts in various concentration. Moreover it seems to be necessary to get informations of the fiber content in the lungs of men. In this investigation 22 dusts, which were isolated by formamide-methode from lungs, were analysed. Methods of preparation and evaluation of the lung dust of people, which were occupational non-asbestos-exposed, are described. Fiber concentration per mg lung dust lies between 10 X 10(3) and 535 X 10(3). Most of the fibers were shorter than 10 mum. Because of the limitation of the evaluation-technique it was not possible to analyse the fibers with regard to their chemical composition.

Paraquat induced lung damage in guinea pigs was used as experimental model producing respiratory distress syndrom. Lung specimens investigated in early stages after this injury showed hyaline membranes combined with hematoxylin bodies. The latter result from epithelial necrosis and local deficit of lysosomal enzymes with reduced cell degradation. Hematoxylin bodies consist of nuclear debris forming spherical bodies by their high surface tension. Their structure is the same as in human newborns where sometimes basophilic bodies are to be recognized in the beginning of pulmonary hyaline membranes.

(1) The mean content in benzypyrene (bp) of human pulmonary tissue amounts to 0.2 mug./100 g. of dry substance. As in all other organ tissues, however, the content differs with the age of the individual: in infants, we find maximum concentrations, in the medium age groups the levels decline and rise once more with increasing age. (2) No increase in the 3,4-benzpyrene levels (average: 0.2 mug./100 g. of dry substance) will be found in tissues with high cellular proliferative activity, such as exocrine and endocrine glands (pancreas, testicles, thyroid gland, adrenals, mammary glands, as well as bone marrow). (3) In human adipose tissue, as well as in that of pork and beef, the 3,4-benzpyrene levels are found to be exceedingly low. With values of 0.1 mug./100 g, the average concentrations lie markedly below the organ tissue levels. Hence, this class of noxious substances in not stored in the adipose tissue. (4) Both in man and in animals (pig, fowl), the 3,4-benzyprene concentrations consistently exceed the average values during early postnatal life. (5) This relatively high concentration of bp in early infancy is due to exogenous factors and is not the expression of biogenous synthesis, as has been demonstrated in examinations of the environmentally influenced embryonic development of the chick. Throughout the entire development of the embryo within the hen's egg, the benzpyrene levels remain constant. Only when the chickens have been hatched out do the benzyprene levels rise significantly. Thus, the low 3,4-benzpyrene levels detected in all human and animal organ tissues prove to be the result of the interplay of exogenous environmental loading and individual capability of eliminating this substance.

In 27 patients it was experimentally demonstrated that after an i. m. injection of 80 mg tobramycin concentrations are obtained in human lung tissue which for about two hours are higher than the minimal inhibition concentration of most gramnegative organisms. In 14 samples of the latissimus dorsi muscle no detectable tobramycin concentrations were found up two hours after injection of the same dose. The ratio of whole blood concentration and lung tissue concentration is 2 : 1. The measurement of tobramycin concentration in whole blood thus enables the concentration in lung tissue to be estimated. The results show--like all serum and tissue level assays--a high individual variation, which might be dependent on the non-defined factors of binding or metabolism, especially as during the examination period of two hours no concentration balance is accomplished between the two compartments. Administration of 80 mg tobramycin i. m. every six hours is recommended in patients with pulmonary infections due to gramnegative organisms.

For successful treatment of bacterial lung infections the administered antibiotic must reach sufficiently high concentrations in lung tissue. Therefore, the concentrations of enoxacin in this tissue were measured in ten patients requiring pulmonary surgery. In order to prevent postoperative infection, the patients received 400 mg enoxacin b.i.d. for three days. Eight h after the final dose samples of venous blood were drawn and a sample of lung tissue was removed. Using a microbiological assay, we found the following concentrations (mean +/- S.D.):serum 2.36 (+/- 0.65) mg/l, lung 6.48 (+/- 1.54) mg/kg. With the HPLC-technique the corresponding values method were 2.37 (+/- 0.80) mg/l and 7.41 (+/- 3.01) mg/kg. Thus concentrations of enoxacin in lung tissue are about three times higher than the corresponding serum concentrations.

Between November 1978 and June 1979 a total of 150 tissue sample (subcutaneous adipose tissue, perinephric fat, liver, lung and muscle tissue) from 30 autopsy cases were examined for their content of volatile organic chlorinated compounds. The ages of the deceased ranged from 29 to 82 years, whereas the majority was 60-70 years old and most were male. Volatile organic chlorinated compounds are detected in all tissue samples investigated. The compounds chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethylene and tetrachloroethylene are always found. The mean values vary between 2 and 25 micrograms/kg wet tissue. The values increase from carbon tetrachloride over 1,1,1-trichloroethane, trichloroethylene and tetrachloroethylene to chloroform. With the exception of 1,1,1-trichloroethane much lower values are found in the liver, lung and muscle tissues than in the fatty tissues. The mean value of chloroform detected in subcutaneous adipose tissue amounted to 23,4 micrograms/kg wet tissue, in perinephric fat 24.8 micrograms/kg, in liver tissue 10.8 micrograms/kg, in lung tissue 9.9 micrograms/kg and in muscle tissue 10.0 micrograms/kg. Maximum values are 10 to 20 times higher. The chloroform content of the tissues increase with age and reach a maximum between 50 and 70 years of age. This increase is not influenced by the fat content of the tissues.

The morphological lung changes of guinea pigs, exposed about 10 days to an aerosol of lipiodol ultrafluid were investigated with light microscopy and enzyme histochemistry 3, 10, 18, 25, 32, 38 and 46 days later. There was a prominent diffuse ore focal thickening of alveolar septa by accumulations of macrophages. Important are changes on the vascular endothelium of muscular pulmonary arteries with swollen and vacuolised endothelial cells. Around pulmonary veins accumulations of lymphocytes were detected. With histochemistry slight increase of phospholipids in alveolar epithelial cells was observed predominantly in the first three days after aerosol application. The intensity of the morphological changes showed a time dependent biphasic cycle with peaks of maximum at the 10th and 38th day after applicationof aerosol.

Biopsies from 68 patients suffering from interstitial lung disease were examined with regard to minerals using Energy Dispersive X-Ray Analysis (EDXA). In 31 patients a higher portion of minerals or elements were found as pigments. The interpretation of these findings is difficult. If there is a professional exposition and a reaction of the lung parenchyma the findings could be of clinical value.

Quantitative and qualitative studies on lipids of the lungs were performed in babies who died during the perinatal period. The lungs were divided into organs with and without hyaline membranes respectively. Total lipids, phospholipids, neutral lipids, lecithins and sphingomyelins were determined. The fatty acid composition of total phospholipids and of lecithins is reported. A multivariate analysis of variance was used for the verification of significant differences in lipid content and in fatty acid composition with regard to the histological diagnosis. Taking at least two parameters (total phospholipids and C: 14-fatty acid or lecithin and C: 14-fatty acid into account, the two groups (lungs with and without hyaline membranes) were significantly different at the 5% level. The results are compared as well with the lipid content and composition of fatty acids of normal neonatal lung tissue as with observations regarding the lipids in amniotic fluid. The data obtained are discussed with regard to the development of lung maturity.

The recovery rates of erythromycin after in vitro and in vivo administration were studied comparatively in liver, lung, and kidney. Using buffer standards the recovery rate in homogenates of in vitro administered erythromycin decreased with increasing protein concentration. At constant protein concentration the erythromycin administered recovered correlated linearly. Mincing the tissues with scissors was not found to be adequate, even when followed by a diffusion period of up to 24 hours. Similarly, shock freezing resulted in lower values. Even and optimal breaking down of tissues was found after homogenisation or ultrasonics. The recovery rates were not raised by treating the tissue with trypsin. There was no evidence of enzymatical erythromycin degradation in liver homogenates under the assay conditions.

In this work, we have studied the occurrence of acid and neutral cysteine proteinase inhibitors in 3 histologically different lung cancers. The acid cysteine proteinase inhibitor ( ACPI ) seems to be associated to squamous differentiation as our previous observations have shown. As a new observation we could show that the neutral cysteine proteinase inhibitor ( NCPI ) was localized in alveolar macrophages.

Dipalmitoyl lecithin (DPL = DPPC, dipalmitoyl phosphatidyl choline) is both quantitatively and functionally the most important constituent of the surfactant complex. The effect of thyroxin (T4) on fetal lung maturity was investigated by means of selective DPL determination. Following administration of thyroxin to the mother animal an increase in the DPPC content was demonstrated in rat fetuses. This increase was greater than that of the total phospholipids. This effect of thyroxin could be due to the following causes: 1, Earlier and accelerated differentiation of lung cells: more Type II cells are formed earlier and these synthesize DPPC more effectively than other lung cells (approx. 40-50% of the phosphocoline in Type II cells in DPPC). 2. Stimulation of the deacylation-reacylation cycle. 3. A combination of these mechanisms.

The present paper describes a simple method for the extracorporeal hypothermic perfusion of isolated lungs during the experimental lung transplantation in the dog. Two different solutions were used: sodium chloride-solution and Dextran-electrolyte-solution. The temperature of the perfused lung falls to 14 degrees C. The water-content is significantly increased by using the sodium chloride-solution, it is slightly increased after perfusion with Dextran-electrolyte solution. The total phospholipid-content is decreased in lungs perfused with sodium chloride-solution, it is significantly increased in lungs perfused with Dextran-electrolyte-solution.

Recent findings of thromboplastin (TRPL) investigations are presented in a brief survey. After enumerating the possibilities of separating this lipoprotein into two shares, the chemical characterization of protein and lipid fraction is represented, the possibilities and conditions of recombining both shares are mentioned and the effectiveness of TRPL in the exogenous coagulation system is illustrated. Furthermore, the liberation of TRPL by leukocytes is referred to and feasible mechanisms of this liberation are discussed. Finally the relations of TRPL to tumour cell materials promoting coagulation and from amnion liquid are discussed.

14 organs and tissues of the rat were tested for inhibitors of the respiratory chain. Electron transfer particles (ETP) from beef heart mitochondria served as test object. The respiratory measurements were carried out in the presence of serum albumin to avoid the reversible inhibition by fatty acids. Inhibition of the NADH oxidase system was observed with testicle, ovary, placenta, amnion, mammary gland, sceletal muscle, skin, liver, kidney, spleen, lungs and brain; the succinate oxidase system was inhibited by preparations from testicle, placenta, amnion, mammary gland, sceletal muscle and skin. Moreover, a self-inhibition of the succinate oxidase activity of the homogenates was observed with brain, liver and placenta. The respiration of the homogenates was inhibited by the respiratory inhibitor RF from rabbit reticulocytes in any case tested. With some objects besides inhibitions also stimulatory effects on the respiration of ETP appeared (vesicular gland, sceletal muscle, spleen, lungs). The inhibitory activities of the rat organs and tissues disappeared in most cases by heat treatment (10 min, 60 degrees C). A part of the inhibitors was sensitive against storage as well as freezing and thawing. They might be lipids (e.g. slow irreversible inhibition by fatty acids not relieved by serum albumin) or inhibitory proteins like RF and enzymes (proteinases and phospholipases). A protein nature is likely for the NADH oxidase inhibitors from liver, kidney, lungs, brain, sceletal muscle and placenta as well as for the succinate oxidase inhibitor from testicle. The results presented suggest the universal distribution and action of endogenous respiratory inhibitors. Presumably they occur in all mitochondria-containing cells. Their primary biological importance may be the triggering of the degradation of mitochondria. High inhibitory activities are present in cells with a high rate of renewal of the mitochondria and furthermore in maturation, differentiation and involution processes which are accompanied by a decline of the number of mitochondria.

The aim of our study was to investigate the interferoninducing effect of aerogenic or oral uptake of influenza viruses in animals. NMRI-mice were infected with mouse-adapted influenza viruses (A/PR/8/34, H1 N1) by aerogen and oral route. In one-day-intervals interferon titers were determined in lung lavage fluids and in lung tissues within nine days after infection. The aerogenic infection led to an increase in interferon followed by a plateau and followed by a slope. The same course of interferon given in lower values was seen in animals after oral virus uptake. The results support the idea of a stimulation of local defense mechanisms in the lung after oral antigen uptake.

Own experiences in practical application of immunohistochemistry are demonstrated in cases of lung fibrosis, sarcoidosis, tuberculosis and allergic vasculitis. Methods for demonstration of immunoglobulins (IgG, IgE) are useful in diagnosis of allergic vasculitis (IgG) and allergic alveolitis (IgE). Lysozyme is an important morphological parameter for the estimation of the activity of sarcoidosis. First results of application of antisera against mycobacteria and Kveim antigen are discussed in respect to more precise differential diagnosis of granulomatous lung diseases (sarcoidosis, tuberculosis).

In all traditional methods of determining fetal lung maturity the content of phospholipids in the amniotic fluid is used as parameter. The function of the other parts of the surfactant is not taken into account. The dynamic surface tension measurements using the Wilhelmy balance simulate the interplay of the whole biological system. We have tested 76 specimens of amniotic fluid and 17 lung extracts from 25 weeks' gestation onwards using the biomechanical procedure. In addition, the L/S ratio in the amniotic fluid was determined. There was a correspondence between the values of the amniotic fluid and the lung measured in the same week of pregnancy. The results of the surface tension measurements show a good correlation with the standard method. The following are the advantages of the Wilhelmy balance: results show a small range of dispersion, procedure can be easily learned and carried out quickly and simply.

The 1N-TMS-omegan-TFA-derivatives of indolalkylamines are suitable for estimation by combined gas chromatography and mass spectrometry for two reasons, viz. (1) Under electron impact charge stabilisation at the indole nucleus is favoured, so structure-specific ions form the base peak. For unsubstituted indoles m/e values of 202 are found and for hydroxyl-substituted indoles m/e values of 290. (2) The calibration curves of the derivatives are linear, even in the femtomole range. The 1N-TMS-omegan-derivatives can easily be obtained by trimethylsilylation with N-methyl-N-trimethylsilyltrifluoroacetamide containing catalytic amounts of N-trimethylsilylimidazole followed by acylation with N-methyl bis(trifluoroacetamide). The serotonin concentrations in different rat tissues are determined by this method of selective omegaN-trifluoroacylation-1N-trimethylsilylation and compared with the values obtained by pertrimethylsilylation.