[Characterization of ipriflavone structure by instrumental examination]. / Az ipriflavon szerkezetének jellemzése müszeres vizsgálatokkal.

The elucidation of the chemical structure of lpriflavone was carried out by ultraviolet absorption spectrophotometric, infrared spectroscopic, 1H and 13C nuclear magnetic resonance spectroscopic, low and high resolution EI mass spectrometric, thermoanalytical, elemental analytical and X-ray diffraction methods. The results unambigously verify the structure of Ipriflavone.

Effect of dietary fat and monoclonal antibody therapy on the growth of human mammary adenocarcinoma MX-1 grafted in athymic mice.

A diet containing 11% per weight fish oils (Max-EPA) reduced the rate of growth of a transplantable human breast tumor (MX-1) grafted into immunodeficient mice (BALB/c, nu/nu) when compared to MX-1 tumors in mice fed polyunsaturated (corn oil) and saturated (lard) fatty acids; however, there was no difference between the corn oil and lard animal groups. Treatment with a cocktail of monoclonal antibodies (MoAbs) decreased the rat of growth of MX-1 in the corn oil fed animals but not in those fed lard or Max-EPA, but the rate of tumor growth of the Max-EPA treated group, either MoAb treated or not, was slower than that of the corn oil and lard groups.

Effect of dietary menhaden oil on tumor cell loss and the accumulation of mass of a transplantable mammary adenocarcinoma in BALB/c mice.

A reduction in the size of transplantable mammary adenocarcinoma IX was achieved when female BALB/c mice were fed isocaloric 10% fat diets containing either hydrogenated cottonseed oil (HCTO) or menhaden oil (MO) as opposed to those mice fed corn oil (CO). Indeed, CO increased the size of the neoplasms when fed alone at 5 or 1% of the diet, although such diets contained less fat calories than did the 10% fat diets containing the other two oils. At the 10% level of dietary fat, enhanced accumulation of tumor mass was observed even when 7.5, 5.0, and 2.5% CO was administered in combination with either HCTO or MO. Although this effect of CO could not be inhibited when nine times as much HCTO was added to the diet, such growth enhancement was abolished when the diet contained nine times as much MO. Hence these experiments emphasized the importance of the type rather than the amount of dietary fat. Whereas MO contained polyunsaturated fatty acids (PUFA's) [approximately 1% as linoleic acid, approximately 16% as 5,8,11,14,17-eicosapentaenoic acid (EPA), approximately 11% as 4,7,10,13,16,19-docosahexaenoic acid (DHA)], HCTO contained none and CO had about 60% of its constituent fatty acids in the form of linoleic acid. The rate of tumor cell loss, determined by the [125I]5-iodo-2'-deoxyuridine method, in the 10% MO-fed or the 10% HCTO-fed mice (54 or 45%, respectively) was more than twice that observed for tumors from the 10% CO-fed mice (22%). These observations were discussed in terms of the influence of the dietary PUFA linoleic acid [C 18:2 (No. of carbons:No. of double bonds), n-6], the PUFA EPA (C 20:5, n-3), and the PUFA DHA (C 22:6, n-3) on the size of mammary tumors and on the involvement of prostaglandins in this process.

Perturbations in cancer cell deformability and resistance to shear forces.

During hematogenous metastasis, circulating cancer cells appear to be killed in the microcirculation by a non-exclusive mechanism, involving the mechanical trauma consequent upon cancer cell interactions with the vessel wall. Various observations by others indicate that with increased cell deformability, there is decreased intravascular cell killing. We have therefore critically examined the effects of agents previously shown to modify cell deformability, on the susceptibility of Ehrlich ascites tumor and L1210 leukemia cells to mechanical damage on passage through polycarbonate membranes in vitro. Treatment with neuraminidase, trypsin or EGTA, was previously shown to increase cell deformability. However, in the present studies, neuraminidase treatment was associated with increased cell loss on filtration; trypsin treatment with small decreases in cell loss, and EGTA treatment with decreased loss. Consideration of the effects of these agents on cell deformability and membrane strength suggests that under the described experimental conditions, the latter appears more important for survival than the former. As proteolytic and glycolytic enzymes and calcium ions are involved in the release of cancer cells from tumors and invasive events, the effects described here may be relevant to the variability of cancer cells with respect to the metastatic process.

Effect of dietary fat on growth kinetics of transplantable mammary adenocarcinoma in BALB/c mice.

The growth of mammary adenocarcinomas in BALB/c mice fed a diet containing 10% corn oil (CO), which has about 60% of its fatty acids as linoleate, was significantly greater than that for tumors in mice fed diets containing either 10% hydrogenated cottonseed oil (HCTO), which has no linoleate, or 10% CO plus 0.003% indomethacin (IM). The proportion of the tumor occupied by the various cell types was quantitated from histologic sections for 2 different mammary adenocarcinomas. At 2 weeks post implantation the degree of inflammatory cell (IC) infiltration of the first adenocarcinoma (tumor IX) did not account for the difference in tumor mass induced by dietary fat. This conclusion was confirmed by a study of a group of tumors arising from hyperplastic alveolar nodule transplants, which showed a similar dietary response but in which IC infiltration was minimal even in the largest tumors. Cell cycle parameters of tumor IX were determined by the fraction-of-labeled-mitoses (FLM) procedure. No differences were found in the duration of the G1, S, G2, or M phases of the cell cycle or the total cell cycle time in neoplasms from the CO and HCTO diet groups. The fraction of tumor cells dividing in neoplasms from the 2 diet groups was also identical. The only parameter that was significantly different was the rate of tumor cell loss when determined by both indirect (FLM) and direct [( 125I]iododeoxyuridine) methods. Tumor cell loss for adenocarcinomas from mice fed HCTO or CO plus IM was approximately twice that obtained for tumors from the CO-fed mice. These observations on tumor cell loss were discussed in terms of: the influence of dietary linoleate on the size of mammary tumors and the involvement of prostaglandins in this process.

Mechanically induced trauma suffered by cancer cells in passing through pores in polycarbonate membranes.

As mechanically induced trauma to cancer cells passing through the micro-circulation may well modify their metastatic behavior, we have categorized the damage done to cultured L1210 and Ehrlich ascites tumor cells passing through 5-12 micron pores in polycarbonate membranes, as a simple, albeit limited in vitro mechanical model. It was shown that in passing through membrane pores, impaired cell reproductive integrity and 3H-thymidine incorporation were the first detected signs of trauma, followed by impaired protein synthesis (14C-labelled amino acid incorporation) and finally, impaired plasma membrane integrity (loss of trypan blue exclusion). This, together with consideration of whole cell and nuclear diameters, suggests that damage may be the consequence of traumatic spatial dissociation between components of the cell periphery, the cytoskeleton and nucleus. Following a single filtration and return to culture, there was a progressive decline in cell numbers up to 96 h. After this, the survivors remained in a 'dormant' steady state for a further 5-6 days, and only then began to divide. The induction of a 'dormant' state in cancer cells by mechanical trauma, analogous to that inflicted in the passage through the microvasculature, is as interesting as it is unexpected.

Survival of L1210 and Ehrlich ascites cancer cells after mechanical trauma is a random event.

Mechanical trauma in the microcirculation is thought to contribute to the inefficiency of the metastatic process in terms of cancer cells. In order to study some aspects of the kinetics of cancer cell destruction in passing through narrow pores, we have developed a model system in which cancer cells are passed through polycarbonate filter membranes in vitro. Filtration through 5-micron pores causes immediate internal damage, reflected in the arrest of active cellular metabolism and reproduction, followed by loss of plasma membrane integrity and, ultimately, the death of the majority of the cells. In this communication, we address the question of whether survival from mechanically initiated filtration damage is a random event, or whether it is a manifestation of a subpopulation of cells, with hereditary resistance to mechanical trauma. Studies on the patterns of cell survival after repeated filtration, and comparisons of the filtration resistance of clonal derivatives developed from filtration survivors with original 'wild' populations, indicate that survival from mechanical trauma is a random event and that resistance to trauma is a nonhereditary property.

[Clinico-pathological analysis of Amanita phalloides poisoning cases in Hungary during 1960-76]. / Az 1960--76. évi gyilkosgalóca-mérgezések klinikopatológiai elemzése.

Cases of intoxication with Amanita phalloides are analyzed in the 17-year-period-material of the Department of the Forensic Medicine of the Semmelweis Medical University and the Department of the Urgent Internal Diseases of the Municipal Korányi Sándor and Frigyes Hospital. The findings show that the number of intoxication with mushrooms during the last years increased. Pahtomorphological changes were also analyzed. Results of the treatment in intensive care units are also discussed.

[Permeability of post-ischemic aortic wall in rats]. / Postischaemiás patkány-aorták permeabilitásának vizsgálata

Examinations were carried out in order to reveal details of process of the permeability damage, its degrea and fate of the plasma-substances getting into the vessel all. Abdominal aorta has been cross-clapped for one hour by the aid of a double ligature. In a recirculatory period from 1 hour to 10 days material serving for labeling of the plasma has been determined in the vessel using histochemical and microchemical methods. Colloidal iron was administered to animals one hour before removing the aorta. The highest quantity of colloidal iron in the aortic wall could be revealed after 24--48 hours of recirculation. By the 10th day the vessel wall contained physiological iron quantity. Colloidal iron administered on the second day of recirculation--when damage to permeability is most marked--in the early phase could be seen in the whole aortic wall. By the 7th day it could be detected only in the outer part of media and in the adventitia. Endothelium inhibits the flow of plasma-substances into the vessel wall, when they got through it, only elastic lamina form a temporary mechanical obstacle for transfusion.