[Analysis of data on a group of patients with multiple myeloma 1977-1985].
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Biomedical subjects
Publications and source records attributed to I Nagy.
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Energy-dispersive X-ray microanalysis was performed on human biopsy materials taken during laryngoscopic intervention in 18 cases. The removed tissue pieces were divided into two parts. One of them was used for pathohistological studies, the other was processed for X-ray microanalysis by the freeze-fracture freeze-drying method. Of the cases investigated 4 proved to be of benign character, whereas the rest contained carcinoma planocellulare keratoides or non-keratoides. Bulk specimen energy-dispersive X-ray microanalysis of 135 cells from the benign tissue samples revealed an average Na+/K+ molar ratio of 0.13 +/- 0.01 (SEM) in the intracellular space, with a regular Gaussian distribution. In the cases of carcinomas 641 cells were measured, the average of the same ratio was 0.67 +/- 0.03 (SEM) due mostly to an increase in the Na+ content. The distribution of data was apparently not normal in the cancerous samples. These observations and some theoretical considerations support the notion that the intracellular Na+/K+ ratio correlates with the proliferative capacity of tissues. The relevance of some recent biochemical results is also discussed in this respect.
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A consistent chondrogenesis takes place in micro high-density cultures of chick limb bud mesenchyme cells stage 22-24. The effect of an increased generation of OH(.) free radicals by Fenton reaction was tested in these cultures. Components of Fenton reaction (i.e., ferrous iron in form of ADP-Fe2+ complex in 0.1 mM concentration, or 0.2 mM H2O2, or the combination of these components with each other, as well as with 0.2 mM ascorbate) were supplemented to the culture medium after the first 24 h. ADP-Fe2+ complex resulted in a drastic decrease of the frequency and confluence of the cartilage nodules seen in light microscope, accompanied electron microscopically by a strikingly increased frequency of occurrence of lipofuscin-like, residual bodies in the cells. Biochemical methods revealed a significant decrease of both the DNA and glycosaminoglycan contents (to 48.6 and 20.7% of the controls, respectively), in day 6 cultures. H2O2 alone caused similar alterations of the cultures, whereas the combination of it with ADP-Fe2+ complex proved to be lethal for the cells. Ascorbate when added to the ADP-Fe2+-treated cultures displayed a slight protective effect for the glycosaminoglycan content but not for DNA. The results are interpreted in terms of free radical theory of aging.
Cultured cells from adult rat anterior pituitaries and intermediate lobes were treated with proteinase inhibitor substrate analogues (Boc-DPhe-Pro-Arginal [BOC-DPPA], DPhe-Pro-Arginal [DPPA], BOC-DPhe-Leu-Lysinal [BOC-DPLL], BOC-DPhe-Phe-Lysinal [BOC-DPPL]) to elucidate their effect on cell morphology. It was established that BOC-DPPA and DPPA (which in previous studies stimulated alpha-MSH release [6]) caused a slight decrease in the number of immunoreactive secretory granules in melanotrophs. BOC-DPLL, which inhibited growth hormone and prolactin release, did not alter the fine structural features of cultured cells. No difference was observed in the membrane turnover traced by cationic ferritin when cells were treated with BOC-DPPL. We suggest that substrate analogues used are harmless to pituitary cells.
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Disturbances of blood coagulation often occur in various malignancies. Deep vein thrombosis or pulmonary embolism often precedes the manifestation of a solid tumour. Chemotherapy, irradiation, surgery, infections are the triggering factors of a blood clotting abnormality. In the present paper the plasmatic clotting factors and platelet functions were studied in patient with solid tumour and with lymphoma. The most characteristic findings were: ethanol positivity, increased fibrinogen level, decreased euglobulin lysis, impairment of platelet functions. In solid tumours the signs of hypercoagulability were more expressed, in non-Hodgkin lymphomas the platelet functions were decreased. These data were in good correlation with data in the literature: in tumours and lymphomas an activation of blood clotting and platelets can be observed.
Haemostasis was studied in 26 patients with malignant non-Hodgkin lymphoma and 19 patients with solid tumours before, and for four days after combined chemotherapy. After treatment an activation of haemostasis was observed in both groups, especially on the 1st and 2nd days. Activation was more expressed in the lymphoma group. This manifested with an increased fibrinogen level, positivity of the ethanol test, a prolongation of thrombin time, an increase of euglobulin lysis and of some platelet functions. Prothrombin and AT III activity decreased as signs of consumption. Thromboembolic events were in the lymphoma group in connection with combined chemotherapy. Thus for preventing the activation of haemostasis we suggest a low-dose subcutaneous heparin treatment for 4 days, beginning 2 h before cytostatic therapy.
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This lecture was aimed to commemorate the centenary of the birthday (18 September 1886) of Fritz Verzár, one of the most important European founders of experimental gerontology. He was an exceptionally creative scientist who contributed considerably to the development of physiology in this century: he achieved important results in the fields of intestinal absorption, in the adrenal gland's function, and finally, from 1952 until his death (1979), he was creator, promotor and one of the best leaders of experimental gerontology. His idea about the age-dependent cross-linking of protein molecules as a general cause of cell aging--studied by him mainly using the collagen as a model, however, extended also to the nucleoproteins--was a pioneer's work. Yet, its significance was not immediately recognized, the contemporary scientists could not interpret his thoughts in the terms of test-tube biochemistry. However, about a decade later, in the sixties and afterwards, an increasing body of evidence has been accumulated indicating that Verzár was right: the most general age-dependent alteration of the proteins in the living systems known so far is a posttranslational modification of their structure and conformation due to the aggressive effects of the oxygen free radicals. Consequences of these thoughts are being realized nowadays in theory and practice. The present generation of scientists expresses its respect and recognition to Fritz Verzár whose life and activity have been teaching us that aging can be understood, if we find the proper theoretical approach to it.
In 53 patients suffering from recurrent thrombosis various hemostaseological parameters were investigated. In 91 per cent of the patients spontaneous fibrinolytic activity was decreased. Decreased or lacking activity of the fibrinolytic system following venous occlusion was found in 48 per cent. In most cases, the concentration of alpha 2-macroglobulin was reduced. This was most pronounced in patients with antithrombin III deficiency. In nearly all cases the concentration of alpha 2-antiplasmin was enhanced. Prospective long-term studies on the importance of defective fibrinolysis are required.
Although X-ray microanalysis represents a useful tool for identifying electron dense histochemical end-products, quantitative microanalytic measurements are seriously hampered in the case of the activities of certain membrane-bound enzymes. For example, the electron histochemical methods revealing K+-dependent pNPPase activity result in a very fine, granular reaction product of lead phosphate. Therefore microanalytic, densitometric of similar evaluations of the reaction, even in semiquantitative terms are not practical by the usual procedures. This paper describes a method of X-ray microanalysis of thick sections (0.5 micron) processed for K+-pNPPase, where a sufficient amount of lead is present for X-ray microanalytic determination. The analysis is performed in the line scan mode on transversely cut membrane profiles by means of the line scan ratemeter of an EDAX System F. This yields quantitative data on the relative lead concentrations in the vicinity of the cell membrane. A method is proposed for calculation of relative enzyme activities based on the Pb-signal of the ratemeter curve and the average "noise"-level of the cytoplasm, containing also non-specifically bound lead. This method avoids the necessity of measuring the section thickness; it may be useful for a variety of purposes in the electron microscopic histochemistry of membrane-bound enzymes.
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Iron as ferrous ammonium sulfate was injected into the cerebral spinal fluid of rats. After three consecutive days of injection of 4 mumol of iron, the total iron content of brain cortex synaptosomes from the iron-treated animals was 2-fold higher than that from control animals receiving the saline vehicle only. Spin label studies of the synaptosomal membranes demonstrated that the lipid region of the membranes became more rigid and, in addition, the mobility of labeled SH groups of membrane proteins decreased after the iron treatment. The cholesterol content was significantly higher in iron-treated animals as compared to controls. Centrophenoxine pretreatment (100 mg/kg body weight daily for 6 weeks) diminished the iron effects. Synaptosomal membrane alterations observed after iron treatment were similar to changes observed previously during aging. This lends support to the notion that free-radical induced damage occurs in brain membranes with increasing age.
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