["Siamese twins". The connection between sterility and reproductive technics].
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Biomedical subjects
Publications and source records attributed to U Winkler.
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Cell proliferation and vascularization were studied in 10 human breast carcinomas by an immunoenzyme technique. The monoclonal antibody (MAb) Ki-67 was used as a marker for proliferating cells and a polyclonal antibody directed against human von-Willebrand factor to identify blood vessels. The proportion of Ki-67-labelled cells varied from 1% to 20%, the number of small blood vessels from 4.4/mm2 to 57.6/mm2. Within single histological sections of individual tumours the percentage of proliferating cells was not related to the number of small blood vessels. However, after evaluation of 5 sections of each tumour, the average values showed that tumours with a high grade of vascularization had a higher percentage of Ki-67-positive cells than poorly vascularized samples. The influence of vascular density on cell proliferation was investigated in a selected area of one of the tumours (in 2-dimensions) and with regard to the over- and underlying sections (in 3-dimensions). After 2-dimensional evaluation, distances from proliferating cells to the closest blood vessel between 10 and 390 microns were observed, and after 3-dimensional evaluation none of the proliferating cells measured was located more than 130 microns away from the closest vessel.
To kill other cells, lymphocytes can exocytose granules that contain serine proteases and pore-forming proteins (perforins). We report that mechanism-based isocoumarin inhibitors inhibited the proteases and inactivated lysis. When inhibited proteases were restored, lysis was also restored, indicating that the proteases were essential for lysis. We found three new lymphocyte protease activities, "Asp-ase,""Met-ase," and "Ser-ase," which in addition to ly-tryptase and ly-chymase, comprise five different protease activities in rat RNK-16 granules. The general serine protease inhibitor 3,4-dichloroisocoumarin (DCI) inhibited all five protease activities. Essentially all protease molecules were inactivated by DCI before lysis was reduced, as determined from DCI's second order inhibition rate constants for the proteases, the DCI concentrations, and the times of pretreatment needed to block lysis. The pH favoring DCI inhibition of lysis was the pH optimum for protease activity. Isocoumarin reagents acylate, and may sometimes secondarily alkylate, serine protease active sites. Granule proteases, inhibited by DCI acylation, were deacylated with hydroxylamine, restoring both the protease and lytic activities. Hydroxylamine does not restore alkylated proteases and did not restore the lytic activities after inhibition with 4-chloro-7-guanidino-3-(2-phenylethoxy)-isocoumarin, a more alkylating mechanism-based inhibitor designed to react with tryptases. It is improbable that isocoumarin reagents directly inactivated pore-forming proteins because 1) these reagents require protease activation, 2) their nonspecific effects are alkylating, and 3) alkylated proteins are not restored by hydroxylamine. We conclude that serine proteases participate in lysis when lysis is mediated by the complete assembly of granule proteins.
It has been suggested that high frequency oscillatory ventilation (HFV) might improve gas exchange and reduce the risk of pressure-related side-effects compared to conventional mechanical ventilation (CMV). Whereas most studies have used arbitrarily set frequencies for HFV, we evaluated the effects of HFV near resonant frequency (fr). Anaesthetised and tracheotomized adult rabbits (n = 10; 3.8-5.1 kg body weight) were ventilated by alternating periods of CMV and HFV near fr. Negative ventilator resistance was used for complete resistive unloading of the respiratory system before each HFV period. This enabled a continuous swinging at resonance thus allowing measurement of fr and selection of exactly that frequency for the HFV run. Intra-animal CMV-HFV comparisons (n = 4) were performed on each animal: with healthy lungs at a mean airway pressure (MAP) of 0.5 kPa and after saline lung lavage at MAPs of less than 1.5 kPa; 1.5-1.8 kPa; greater than 1.8 kPa. Surfactant removal caused total respiratory system compliance (Ctot) to decrease from 44 +/- 5 to 22 +/- 3 ml/kPa. Corresponding fr was 244 +/- 48 and 360 +/- 30 min-1, respectively. HFV produced effective pulmonary gas exchange but did not improve arterial oxygenation in comparison with CMV at matched MAPs both before and after surfactant depletion. Volume amplitudes of oscillation necessary to achieve normocapnia were slightly above the natural plus equipment (2 ml) dead space. Maximum intra-alveolar pressure (Pmax) was calculated for the HFV runs from MAP, Ctot, and the volume amplitude of oscillation. Pmax during CMV was nearly twice that during HFV at equivalent PaCO2 and equivalent MAPs throughout the experiments.
In pathogenic studies on acute pancreatitis the importance of a temporary ischemia on induction of autodigestion was demonstrated. Because of the involvement of oxygen-derived free radicals in the ischemia/reperfusion injury of other tissues we have investigated the influence of artificial oxidants, as FeCl3 and H2O2, on pancreatic tissue and isolated pancreatic acinar cells. Lipid peroxidation was determined as thiobarbituric-acid-reactive substances (TBRS). In these experiments the TBRS concentration was elevated within the first min of incubation with FeCl3. The exposure of pancreas homogenates and intact acinar cells to H2O2 had no remarkable effect on formation of TBRS. Under this condition the survival of cells was strongly reduced, while cells exposed to FeCl3 revealed a remarkably slower rate of cytolysis. The missing correlation between cell lysis and elevation of TBRS suggests that lipid peroxidation might not be essential process in pancreatic acinar cell damage.
Morphological and functional results of the factors influencing the nasal mucous membranes of 150 persons living in a tropical zone are presented. In particular, an increased rate of hyperplastic mucosa was found in comparison with a group of 850 subjects from central Germany. The macroscopic results correlated with exfoliative cytological examination. On the other hand, the rates of moderate and severe hyposmia (9.3%) as well as moderate and extreme nasal obstruction (34%) were lower.
The safety of electrocoagulation for laparoscopic surgery has been greatly improved by the introduction of the bipolar coagulation technique. But complications caused by coagulation, especially by the overheated forceps, are still reported. In order to reduce those complications, a temperature controlled bicoagulation system was developed. This system allows coagulation with lower temperatures which can be kept constant during the coagulation process. In experiments with human fallopian tubes obtained by adnexectomy and rabbit uterine horns it is shown that those lower temperatures are sufficient for homogeneous coagulation. On line monitoring of the temperature during coagulation provides the surgeon with the possibility of directly controlling the actual temperature at the tip of the forceps. The temperature curves can easily be stored in order to be able to demonstrate the particular coagulation process even after years.
Ten anesthetized, tracheotomized, adult rabbits were used to test the validity of a method for calculation of total respiratory system compliance from resonant frequency (Cr). Reference values were obtained during constant flow inflation of the relaxed respiratory system by dividing the volume gain by the related difference in pressure at the airway opening (inflation method compliance, Ci). The animals were connected to a new type of servo-controlled infant ventilator. Besides volume-controlled mechanical ventilation at constant inspiratory flow rate and intermittent mandatory ventilation, there is a negative ventilator resistance mode integrated in this device for resistive unloading (Schulze A, Schaller P, Gehrhardt B, Mädler H-J, Gmyrek D: Pediatr Res 28:79-82, 1990). To measure resonant frequency (fr), the respiratory system was totally unloaded for a short period by a negative ventilator resistance exceeding the combined resistances of the endotracheal tube and airways. This evoked a continuous oscillation at fr. By analogy with electrical circuit theory, Cr was calculated according to C = 1/(4 pi 2.I.fr2) where C is compliance and I is inertance. The inertance of the endotracheal tube is given and that of the bronchial tree was ignored assuming a much greater total cross-sectional area and therefore much lower inertance when compared with the endotracheal tube. Three pairs of Ci - Cr values were obtained from each animal: 1) during intact respiratory muscle activity; 2) after pancuronium relaxation, and 3) after surfactant depletion by saline washout.(ABSTRACT TRUNCATED AT 250 WORDS)
2,601 workers with exposure to irritant noxae received a standard occupational rhinolaryngeal check up supplemented with higher specialized methods. The measurements of mucociliary clearance, the screening--olfacto-/gustometry, the cytological investigations of the nasal mucous membranes with the smear technique, and the sonography of paranasal sinuses, too, were qualified for occupational practice. The significance of leading symptoms and the unity of upper and lower respiratory tract are to emphasize.
Sieve analyses have proved that the camomile commercial drug is an extremely heterogeneous material which contains ultracoarse particles greater than 4 mm (aprox. 70%) in addition to fine particles less than 0.71 mm (approx. 15%). The ultra-coarse particles are not usable in tea mixtures. For camomile, it is proposed a homogeneous infusion drug (less than 2 mm). The comminution should be performed in the pharmacy. Where species are mixed with camomile, the particle sizes should not exceed 2 mm. The homogeneity of these mixtures is determined by weight comparison of a series of tea-spoon weights. For the comminution of the drugs the authors suggest the use of a "Retsch" cutting mill or a similar appliance which ensures that only few fine particles to be produced. For the removal of suspended fine particles in the infusum of camomile the use of Cilia filter bags is suitable.
For the recognition of nasal lesions in exposure to non-toxic metallic dusts with crystalline SiO2-content in 100 foundry workers the in vitro determinations of the pH-value as well as the statement of IgA in the serum and nasal discharge were performed by means of simple radial immunodiffusion according to Mancini. The two functional-diagnostic method did not show any significant differences in comparison to the control groups. At present an use in the clinical and occupational-medical practice cannot be recommended.
Between 1986 and 1988 within our therapeutic drug monitoring plasma concentrations were estimated in 1,442 plasma samples by radioimmunoassay. Plasma levels between 0 and 84.2 ng.ml-1 with a mean of 20.8 ng.ml-1 were measured. If the maintenance dose was reduced from 0.1 to 0.07 mg the frequency distribution of the plasma samples was shifted to the left, and the mean value decreased by 5.8 ng.ml-1 (23.5 vs. 17.7 ng.ml-1). The physician's assumptions underdosage?, optimum dosage schedule? or overdosage? were confirmed by the laboratory results in 22.3, 63.6, or 23.0% of the requests, respectively. In 61.2% of all plasma samples were digitoxin concentrations in the range between 10 and 30 ng.ml-1, i.e. in the optimum therapeutic range. Main reasons for the divergent results are non-compliance of the patients and inter-individual differences in the pharmacokinetics of digitoxin. Furthermore, incomplete filling of the forms by the physicians aggravates the assessment of the results. Therefore, a permanent dialogue between clinician and clinical pharmacologist is necessary for an improvement of digitalis therapy.
Mutants of the luminescent bacterial strain NRRL B-11177 were isolated with pleiotropic hypersensitivity towards hydrophobic antimicrobial agents. SDS-PAGE analyses of outer membrane proteins and lipopolysaccharides revealed that the outer membrane structure of the ahs-mutants was altered. QSAR analysis showed that the inhibitory effect of chloro-substituted phenols on bioluminescence of the ahs-mutants depended on their hydrophobicity. The effect of chlorinated phenols and detergents on bioluminescence was increased in the ahs-mutants. The potential use of these mutants in bioluminescent toxicity tests was discussed.
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Using the Prasinophycean algae Platymonas, Heteromastix, Pedinomonas, and Pyramimonas, subcellular distribution of the enzymes of glycolate metabolism and beta-oxidation pathway have been studied. Glycolate dehydrogenase, hydroxypyruvate reductase, and glutamate-glyoxylate aminotransferase are located in the mitochondria. In addition, the mitochondria of all four species contain acyl-coenzyme A (CoA) dehydrogenase, enoyl-CoA hydratase, and thiolase. In Platymonas, Heteromastix, and Pedinomonas, organelles with the characteristic structure of peroxisomes have been detected which also contain the enzymes acyl-CoA oxidase, enoyl-CoA hydratase and thiolase. However, catalase could not be demonstrated in either the peroxisome-like organelles or in the whole cells.
The performance of a new infant ventilator system had to be evaluated. Technically it is characterized by flow (V)- and pressure (P)-transducers mounted immediately near the endotracheal tube. A microcomputer works as a function generator and governs servo-controllers for V and P thus offering a multiplicity of different modes both of the conventional (CMV) and high frequency oscillatory (HFO) type. The additional dead space imposed by the system is identical with its internal compressible volume of 2 ml. Serial pulmonary lavages were performed in 17 adult rabbits while on CMV. PaO2 per unit of mean airway pressure (MAP) decreased thereby from 95.9 +/- 29.3 to 9.0 +/- 6.7 (kPa/kPa). The animals were then alternately ventilated by HFO (5, 10, or 20 Hz) and CMV, at matched MAP's. No significant difference in PaO2 between the two methods was revealed in intra-animal comparisons except a slight superiority of CMV at MAP's above 1.7 kPa (P less than 0.05). There was no clear linear relationship between PaO2 and MAP both at CMV and HFO. A strong increase in PaO2 often occurred beyond a MAP threshold. In 37 postlavage HFO runs at 5 Hz in 13 animals volume amplitudes of 3.19 +/- 0.5 ml/kg of bodyweight resulted in PaCO2 levels of 6.29 +/- 1.87 kPa. Except in one experiment (10 Hz) volume amplitudes below the natural dead space produced arterial hypercapnia.
For the purpose of registration of subjective complaints and pathological changes of the respiratory tract 1,023 employees of socialist agriculture were additionally examined in connection with an expanded x-ray-screening from the points of view of otorhinolaryngology and industrial medicine. The employees in industrial livestock breeding, especially in industrial poultry breeding, turned out to be the group with the most frequent complaints and pathological findings in the respiratory tract. The findings suggest, that chronic, non-specific changes develop on the basis of the summation of several noxious factors in industrial live-stock breeding. In conclusion of the examination recommendations for the optimization of the working conditions for employees in industrial livestock breeding are given from the points of view of industrial hygiene and occupational medicine.
One hundred patients were inspected after anamnesis by the mirror test by Glatzel, by anterior rhinoscopy, and anterior rhinomanometry in order to judge the passage of the nose. The results of the several parameters were compared on the base of an unitary scale. Fifty two percent of the patients had a full and 43% a partial conformity of the parameters. In 5% of all cases all parameters were divergent. The mirror test is available as screening method. The high expressiveness of rhinoscopy and rhinomanometry for the diagnosis of the restricted nasal breathing is explained.