[Myocardial infarct and thrombophlebitis].
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Biomedical subjects
Publications and source records attributed to H Krug.
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Under atherogenic diet in the pig changes of the intima developed in predisposed places of the arteries which have close relations to the atherogenesis in man. 4 months after the end of a 4-month atherogenic diet no decisive regression of lipid infiltrates could be established in spontaneous thickenings of the intima, however, signs of a lipid mobilisation.
We had concluded from former own investigations that the cells in the arteriosclerotic plaque effect a change of the ester proportion of cholesterol. One of the possible mechanisms ible bond and from double unsaturated (linoleic acid) to higher unsaturated acids. Therefore we investigated by radioactive labelling of the fatty acid moity of cholesterol esters whether such desaturation reactions take place in the model experiment. For this purpose we implanted cholesterol stearate which was 14C-labelled in the proportion of fatty acid subcutaneously into the skin of a rat. We demonstrated radiohistochromatographically that after 7 to 14 days the fraction of the cholesterol esters with 1 double bond was additionally labelled. Other fractions were not labelled. From this results that the proportion of the saturated fatty acid of the cholesterol ester is actually desaturated, in which case the desaturation as we expect only goes to the fraction with one double bond, because the double unsaturated linoleic acid is not synthetized in vivo in the mamal.
In 50 formol fixed biopsies from the m. quadriceps femoris normal and hypertensive arteriolosclerotic arterioles were characterized by quantitative histophysical and histochemical methods. The interference microscopical measurements showed a real increase of dry mass concentration in the pathologically changed vessels. Additional histophotometrical results are interpreted as an increase of proteins with higher isoelectric point (globulins, actomyosin). An augmentation of actomyosin is compatible with the medial hyperplasia demonstrated histologically. Likewise a positive correlation was found between the fibrin incorporation proved histochemically and the quantitatively evaluated protein reaction with Fast green; Glycosaminglycans do not carry weight quantitatively. The polarization optical measurements yielded an alteration of the submicroscopical structure in arteriolosclerosis. It consists in a diminution of the submicroscopical volum of gaps and in a diminished orientated dye binding of Congo red. Thereby the pathogenesis of hypertensive arteriolosclerosis of skeleton muscle is above all characterized by an increase of heterogeneous proteins (blood plasma proteins, actomyosin) in the arteriolar wall, leading to a diminution of the submicroscopical volume of gaps and to an elevation of the dry mass concentration.
The resistance of nuclear chromatin against acid hydrolysis with hydrochloric acid was studied in cell nuclei of different organs from young and old rats and after application of cortisol. Suspensions of cell nuclei from liver, spleen, kidney, heart muscle and mucosa from small intestine were stained with ethidium bromide without and after hydrolysis. The relative fluorescence intensity (FI) of every pair was measured by flow through cytophotometry. Always the FI of the diploid peaks of the hydrolysed samples was diminished. The resistance against hydrolysis was greater in old animals than in young. After application of cortisol in vivo in all organs, except in the liver, the resistance against hydrolysis was increased. Only the nuclei of liver from old animals showed a diminution of resistance after cortisol. It is assumed, that the greater resistance in age is due to the diminished functional ability of the nuclear chromatin. In the most organs, the inhibitory activity of cortisol to the cell metabolism is known, only in the liver cell it stimulates the synthesis of RNA and protein. This is in agreement with our findings.
Morphology and DNA content were studied in explantate cultures of normal epithelium, persisting intraepithelial atypias (dysplasias and carcinomas in situ) and carcinomas of the cervix uteri. Intraepithelial atypias and carcinomas can be distinguished from the normal epithelium, growing strictly as a monolayer, chiefly by the primary and secondary loosening of the cellular lawn with increased tendency towards overlapping of cells. DNA determinations provide the possibility of demonstrating, also in vitro, deviations of the DNA content of dysplasias, carcinomas in situ and pavement epithelial carcinomas from the normal epithelium. The findings are in accord with the results which we obtained by in vivo studies and underlinions.
By impulse cytophotometry (ICP) it is possible to get a DNA-distribution curve of nuclei in cell suspensions. The ICP curve directly represents the ploidy pattern of the investigated cell population and, more indirectly the proliferation intensity. For practical tumor diagnosis in cytology by ICP as a first step we must know, wether the ICP is able to detect differences between normal and tumor cells by simple criteria. Together with our clinical coworkers we had investigated cell suspensions from carcinomas of the cervix, ovary, breast, larynx, stomach and malignant melanomas. Approximately one half of these tumors were poly- or aneuploid. In the remaining diploid tumors some did not show signs of strong proliferation in the form of high 4c-peaks in the ICP; for these the chances of detecting by ICP in exfoliative material are low. This is in agreement with our results on vaginal smears. Here we had a good correlation between the mean 4c-height of the ICP curves and the Papanicolaou grading. But mass screening is not the main application of ICP because the security of Pa-grading is more sufficient. In individual problematic cytological cases with repeated investigation ICP is a very valuable diagnostic aid.
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Tumor cell suspensions from 100 biopsies of squamous cell carcinomas of the cervix uteri were investigated by impulse cytophotometry (ICP) after staining with pepsin-ethidium bromide. We estimated the ploidy pattern by comparing the ICP curves with normal diploid material. The originally linearly classified curves were transformed in a logarithmical manner. We found 48 diploid populations and 42 polyploid populations, among them 19 tetraploid tumors. In these the 4c-peak was the highest. In 10 cases there were aneuploid stem lines, mainly lying between 2c and 4c; 2 curves had a hypertetraploid pattern. Helpful for interpretation of the whole curve is the introduction of an index: the "relative mean DNA-content" (DNA). In 15 diploid tumors we found a low proliferating rate, characterized by low 4c-peaks. For interpretation of polyploid cell cycles a completed nomenclature of cell cycle phases was introduced. Comparing our material with chromosome analyses in laterature we found more polyploid, e.g. tetraploid tumors. It can be assumed that the estimation of ploidy pattern solely by DNA measurements has another meaning than by chromosome analyses. The higher ploid peaks in DNA distribution curves (e.g. ICP-karyograms) represent not only true polyploid nuclei but also nuclei which are in a blocked premitotic resting phase (G2 for 4c; G'2 for 8c and so on). The ICP is a valuable method for estimating biological pecularities of tumor cell suspensions.
Atherogenesis is the result of interactions of factors originating from blood stream and the reaction of the arterial wall. Basing on this we have a pathogenetic trias: blood--lining membrane--arterial wall. Under these aspects some modern trends of experimental research are discussed. An example of blood-plasmatic injury is the hyperlipidaemia. The permeability of the lining endothelium regulates the infiltration and is influenced by several factors. The reactions of the modified smooth muscle cells in the arterial wall are the most important events in early atherogenesis. The metabolic decompensation of these cells is a main factor in the transition to advanced lesions. The efficiency of the cells is the preliminary condition for the reversibility of atherosclerotic lesions. Only early stages have some chances of regression; one must bear in mind this together with all therapeutical treatments.
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The catabolism of fibrinogen was studied during the first week of acute myocardial infarction in twenty-three patients and in ten control patients. A trial was carried out using 125I-labelled fibrinogen. After myocardial infarction, the mean biological half-life of fibrinogen was 62.5 +/- 10.0 h and the mean plasma loss of fibrinogen per 24 hours was 34.1 +/- 6.9% of the intravascular fibrinogen pool. In the control group, respective values of 89.6 +/- 9.9 and 23.4 +/- 3.9% were obtained, which were in close agreement with published values for the normal catabolism of fibrinogen. The fractional catabolic rate of the intravascular fibrinogen pool was significantly increased in patients with myocardial infarction in contrast to the absolute plasma loss of fibrinogen which appeared to be the same as in subjects with normal plasma fibrinogen concentration. Possible explanations of the accelerated catabolism of fibrinogen after myocardial infarction are discussed.
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187 women with cytologically suspicious cervical smears (Papanicolaou III to V) were investigated by 387 pulse cytophotometric (ICP) measurements. Within the Papanicolaou III group a significantly higher 4c-peak was seen in cases with only one ICP-investigation if we had histologically pathological findings (dysplasia, carcinoma) as contrastes with clinically and cytologically regressive cases. In repeated ICP-investigations we found in group Papanicolaou III (histol.: dysplasia, carcinoma) as well as in group Papanicolaou IV and V a significantly higher mean 4c-height than in only once investigated cases. Within a ICP-series the maximal 4c-height is most representative. The security of diagnosis is raising with repeating ICP-investigations. Here it is a valuable diagnostic aid especially in suspicious cases. All abnormal ICP-findings must be controlled for a long time, even with normal cytological smears. At last, the circumstances causing false negative ICP-results are discussed.
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25 laryngeal carcinomas were investigated by pules cytophotometry, stained with ethidium bromide after pepsination. The karyograms were interpreted as DNA-distribution curves. In diploid populations the height of the 4c-peak was taken as a measure of proliferation rate. Aneuploidy and polyploidy were estimated by camparison with human diploid material . In our material we found 13 polyploid tumors (under them 6 aneuploid populations from 7 at all). After dividing the cases into two groups (1: with slow, 2: with rapid progression) the moiety of polyploid and aneuploid tumors and the height of the 4c-peak was significantly higher in group 2. The pulse cytophotometry gives reliable additional informations showing the great variability of biological characteristics of laryngeal carcinomas. Possibly this is a basis of a more differentiated therapy.
The changes of the arteries appearing diffusely caused by ageing as a rule favour the development of the focal arteriosclerotic changes. Already due to the increasing blood lipid level the ageing vessel is exposed to increased loads. It is more difficult for it to cope with them, since caused by ageing the cell functions of endothelium, intima and adjacent media decrease, whereas the diffundibility increases. The alterations of the mucopolysaccharide spectre in old age also render difficult the maintenance of the integrity of the arterial wall. The decrease of the distensibility of the arterial wall, partly consequence of increasing cross-linking, partly expression of senile fibrosis, is partially compensated by dilatation of the vascular tube. When arteriosclerotic beds supervene on account of solidification caused by old age additional difficulties appear. On principle the genuine changes caused by old age smooth the way for the development of arteriosclerotic changes.
By flow microfluorometry the DNA distribution curve of the cell nuclei of 39 adnex tumors, mainly ovarian carcinomas, was measured. 47% of the malignant tumor cell populations were diploid, the other ones were heteroploid (i.e. polyploid, tetraploid, aneuploid stem lines). Heteroploid tumors had the worse prognosis. In 8 cases effusions were analysed (7 ascites, 1 pleura). It is possible to diagnose a malignant tumor from effussion fluid by impulse cytophotometry. But in one case a great difference was found between the primary tumor and the ascites fluid, which only shows the DNA distribution of an irritative effusion. The value of impulse cytophotometry for clinical purposes is discussed.