Search PubMed⌕ Search

Biomedical subjects

I Zs-Nagy

Publications and source records attributed to I Zs-Nagy.

At least 19 recordsLinked to original sources
PubMed2002

Hydroxyl free radicals induce cell differentiation in SK-N-MC neuroblastoma cells.

The SK-N-MC cell line is frequently used as a model of neuronal differentiation induced by 5-bromodeoxyuridine (BrdU). In this study, the differentiation properties of this cell line were investigated under hydroxyl free radical generation, and compared to BrdU treatment. Hydroxyl free radicals were generated in the cultures by the Fenton reaction, i.e. by simultaneous addition of ADP-Fe2+ complex and H2O2. Microscopic morphological signs, as well as the acetylcholinesterase and ganglioside sialidase activities were considered as markers of neuronal differentiation of this cholinergic neuroblastoma cell line. Apart from the altered morphological appearance, the marker enzymes displayed significant increases after both types of intervention. We suggest that hydroxyl free radicals can induce in vitro cell differentiation. They apparently play a more complex role in cell physiology than simply causing oxidative damage.

Acetylcholinesterase↗
PubMed2001

Enzyme activities in the light of the membrane hypothesis of aging. [An answer to K. Kitani, Mech. Ageing Dev. 107 (1999), 299-322].

The paper of Kitani cited in the title has raised an apparent contradiction regarding the validity of certain aspects of the membrane hypothesis of aging (MHA). He collected data showing that a number of detoxifying liver enzyme activities, although decline with age in male Fischer 344 rats, remain at an unchanged level in females of the same strain. He concluded that the main assumption of the MHA, according to which intracellular enzyme activities generally decline with age, cannot be maintained, and invoked me (p. 312) 'ellipsis to provide in the future ample (and convincing) evidence' in this respect. The present paper answers this criticism by showing that the apparent contradiction mentioned above is based on a misunderstanding on behalf of Kitani. Namely, MHA speaks about the general, density-dependent decline of the catalytic rate constant of any enzyme (k(cat)), i.e., activity per mole of enzyme, being the true specific activity of the enzymes. This parameter inevitably decreases at the increased physical density of the intracellular colloids during aging. This statement derives from the molecular enzyme kinetic models, and has extensively been proven experimentally, too. On the other hand, Kitani speaks about enzyme activities per mg total protein content of certain tissue extracts, which is a very illdefined parameter, since the concentration of the measured enzyme remains unknown. Therefore, this latter parameter is irrelevant from the point of view of MHA in any aspect.

Aging↗
PubMed1999

The hydroxyl free radical reactions of ascorbyl palmitate as measured in various in vitro models.

The OH(*) free radical scavenging properties of ascorbyl palmitate (AP), water-solubilized in the presence of a surfactant (Brij 35), were tested in various systems: (1) The inhibition of polymerization of bovine serum albumin by OH(*) free radicals generated by the Fenton reaction indicated AP exerts a considerable protective effect against polymerization by scavenging the OH(*) free radicals. (2) ESR spin trapping comparisons of DMPO with AP were conducted. Using the Fenton reaction as a source of OH(*) free radicals, AP was 1 order of magnitude faster in scavenging these radicals than DMPO. (3) Oxidative modification of BSA by (60)Co-gamma irradiation of 80 krad, results in a strong increase in protein carbonyl content. AP inhibits carbonyl formation very efficiently, indicating that AP may be utilized as a biological OH(*) free radical scavenger in human therapy.

Animals↗
PubMed1999

Age-dependence of the lateral diffusion coefficient of concanavalin-A receptors in the plasma membrane of ex vivo prepared brain cortical nerve cells of BN/BiRijHsd rats.

A new method has been developed for ex vivo preparation of brain cortical cells of BN/BiRijHsd rats to make them suitable for the measurement of the lateral diffusion coefficient of the membrane components by means of fluorescence recovery after photobleaching (FRAP). The method involves chopping the brain cortex into pieces of less than 1 mm. These parts are stained with a fluorescent label (e.g., concanavalin-A-fluorescein, Con-A-FL conjugate) and then gently pressed onto a microscope slide using the coverslip. In the resulting specimen, the largest cells of the cortex can be recognized in phase-contrast image, sufficiently stained by the label and ready for the FRAP measurement. The lateral diffusion coefficient of Con-A-receptor proteins (Dp) was measured in such brain cell preparations of 15 female rats in four age groups (5.6-31.8 months) and 11 males in three age groups (13.8-31.8 months). Highly significant negative, linear age correlation of Dp (R=-0.9958 in females, and -0.9956 in males) were found, the regression equations being D(p female) =(8.8311-0.1425 X)(-10) and D(p male)=(9.3240-0.1630 X)(-10) cm2/s, respectively, where X is age in months. The data confirm that the lateral mobility of plasma membrane proteins represents an important biomarker of cellular aging in the brain cortical cells of BN/BiRijHsd rats.

Aging↗
PubMed1998

Age-dependence of the lateral diffusion coefficient of Con-A receptor protein in the skeletal muscle membrane of C57BL/6J mice.

The lateral diffusion coefficient (Dp) of the Con-A receptor protein was measured in the sarcolemma of the quadriceps femoris (QF) muscle of male and female C57BL/6JNia mice in four age groups between 2 and 26 months. Freshly prepared, ex vivo taken muscle strips were stained with Con-A-FL conjugate for 10 min, and fluorescence recovery after photobleaching (FRAP) measurements were carried out on 20-30 cells per animal, at 37 degrees C. Using this technique, Dp, and the fractional recovery (mobile fraction = FR%) of these proteins can be measured. In the youngest male and female age groups, Dp values of 5.72E-10 and 5.43E-10 cm2/s, and FR% values of 43.3 and 36.3%, were found, respectively. Dp displayed a characteristic, significant, negative, linear correlation with age in both sexes. The slope of the linear regression line calculated per month of age was 1.06E-11 and 0.96E-11 cm2/s for males and females, respectively; both of them differ from zero highly significantly. FR% values tended to increase slightly with age, yet the estimated average Dp = D(FR), calculated for the total Con-A receptor pool, maintained its significant, negative, linear age-correlation. The physiological significance of these changes needs to be clarified in the future.

Aging↗
PubMed1997

The membrane hypothesis of aging: its relevance to recent progress in genetic research.

This review outlines the main concepts of the membrane hypothesis of aging (MHA) developed over the past two decades. MHA offers a general cell biological mechanism to explain the main trends of age-dependent changes in terms of intracellular physicochemistry. An essential point in MHA is that the inevitable plasma membrane alterations result in the accumulation of dry mass in the intracellular space, a process that is essential to cellular development and organismal maturation, but which becomes a rate limiting factor above a certain physical density of the cell colloids. The main statements of the MHA are supported by recent developments in molecular genetics. Specifically, the great majority of the products of oncogenes and antioncogenes are localized to the plasma membrane, indicating a central role of the plasma membrane in mitotic regulation, cell differentiation and senescence.

Aging↗
PubMed1996

Relative intranuclear magnesium and phosphorus contents in normal and tumor cells of the human thyroid gland as revealed by energy-dispersive X-ray microanalysis.

Energy dispersive X-ray microanalysis was performed on altogether 42 surgically removed tissue specimens of 32 patients, which were taken either from intact thyroid parts or various histopathologically verified tumors of the thyroid gland. The tissue specimens were processed with the freeze-fracture-freeze-drying technique and then analyzed in the so-called bulk specimen form. The studies were carried out during the years 1980-81, when intranuclear monovalent ionic composition was studied in detail. From the retained total elemental peak list, it was possible to calculate retrospectively the relative intranuclear Mg and P contents. The data processed by nested (hierarchical) analysis of variance show that the intranuclear Mg content of the 5 diagnostic groups (normal thyroid tissue, thyroiditis, benign adenomas, differentiated carcinomas and undifferentiated thyroid tumors) increases significantly, in parallel with the increasing malignancy, but the P content remains unchanged. One can conclude that the elevated intranuclear Mg content in the tumors of high malignancy may be of diagnostic importance, and a warning signal for the therapeutic approaches based on Mg-supplementations.

Cell Nucleus↗
PubMed1995

The influence of dystrophin on lateral diffusion of proteins in sarcolemma of L-185 and C2 myoblasts and mature striated muscle cells of rats and mice, as measured by FRAP technique.

The expression of dystrophin can be suppressed in cultured skeletal muscle cells (coded L-185 from rat, and C2 from mouse) after a proper genetic manipulation. The influence of presence or absence of dystrophin on the lateral diffusion constant of Con-A-receptors was studied in the cell membrane of such cells (and also of mature skeletal muscle fibres of rat and mouse) by means of the fluorescence recovery after photobleaching (FRAP) technique, applying a novel fluorescent label called Con-A-BODIPY-FI conjugate. It has been established that the normal maturation, of myoblasts into skeletal muscle fibres involves a significant decrease of the mobility of Con-A receptors in the sarcolemma. In the absence of dystrophin, this maturation process cannot take place; the membrane proteins display an increasing mobility during the culture time, which is of lethal effect for these cells.

Animals↗
PubMed1995

Induction of age pigment accumulation in the brain cells of young male rats through iron-injection into the cerebrospinal fluid.

The OH free radical formation can be increased in the brain by intralumbar iron injections into the cerebrospinal fluid (CSF) through the Fenton reaction. Ferrous ammonium sulphate was injected to male CFY rats of 3 months of age. The animals survived a single dose of 4 mumoles, and this treatment was repeated daily for 3 or 6 days. The total iron contents of the large brain and the cerebellum were measured by atomic absorption spectroscopy; 3 days of iron administration resulted in significant increases of iron contents only in the cerebellum, whereas after 6 days, both parts of the brain showed considerably higher iron contents. Electron microscopic point-counting morphometric analysis revealed a 65% increase of volume density of the lipofuscin in the large cells of parietal cortex after 6 days of iron-treatment. The Purkinje cells displayed a particularly frequent occurrence of an "apoptosis"-like structural alteration under the effect of iron. This kind of experimental approach is complicated by the facts that (i) the increase of OH radical flux above a certain level is lethal, and (ii) the young animals have a very active elimination mechanism of the waste products. Nevertheless, the enhancement of OH radical yield by an increased availability of iron for Fenton reaction resulted in an accumulation of lipofuscin even in young rats.

Age Factors↗
PubMed1994

Clinical meaning of DNA content in the long term behaviour of follicular thyroid tumours: a 12-year follow up.

OBJECTIVE: To find out if there was any correlation between the DNA aneuploidy in benign tumours and in malignant follicular tumours of the thyroid and the progression of either disease. DESIGN: Retrospective study. SETTING: University hospital. SUBJECTS: 71 of 75 patients who had had cytofluorimetric nuclear DNA analyses done on their follicular thyroid tumours during the period 1977-1980, and for whom clinical follow up data were available. MAIN OUTCOME MEASURES: Correlation between clinical course and finding of aneuploidy in original histological specimens. RESULTS: Aneuploidy was found in 6/40 follicular adenomas, 3/17 adenomatous goitres, and in 13/14 follicular carcinomas. The patients were examined after 12 years, when there had been no recurrences of the benign tumours. 5 of the patients with carcinoma had died of distant metastases, all of whom had aneuploid stemlines. There are, however, 8 patients with carcinomas and aneuploidy who are still alive with no recurrences or metastases. CONCLUSIONS: DNA aneuploidy indicates neither the invasiveness nor the metastatic potential of follicular thyroid tumours, and does not distinguish between the minimally invasive (encapsulated) and highly invasive carcinomas.

Adenocarcinoma, Follicular↗
PubMed1993

Induction of granulocytic maturation in HL-60 human leukemia cells by free radicals: a hypothesis of cell differentiation involving hydroxyl radicals.

Tumor cells usually contain lower superoxide dismutase (SOD) activity than differentiating cells, suggesting the involvement of oxygen free radicals in cell maturation. The effects of a system known to produce the OH. radicals were tested on HL-60 cells cultured under optimum conditions for 96 hr. Hydroxyl radicals were generated by a Fenton reaction, involving an ADP-Fe2+ (or ATP-Fe2+) complex and H2O2. Changes induced by OH. were compared to the effects of DMSO-induced differentiation of HL-60 cells. Cell numbers, viability, thymidine incorporation, TPA-induced NBT reduction and propidium iodide staining in flow cytometry were determined. The OH. generating system inhibited the growth and thymidine incorporation of leukemic cells in a manner dependent on the dose of added H2O2 (from 0.005 to 0.05 mM). In addition, an increasing proportion of the treated cells displayed signs of cell differentiation. In DMSO-treated cells, SOD and catalase activities increased after 6 days of culturing. The results show that a portion of the OH. free radicals derived from H2O2, produced by the action of SOD, may be a necessary prerequisite for differentiation, whereas an overproduction of OH. causes cell lethality or aging. We suggest that OH. free radicals may have a more complex role in cell physiology than simply causing oxidative damage.

Cell Differentiation↗
PubMed1992

Effect of cis-diaminedichloroplatinum (II) (cis-DDP) on the intracellular Na+/K(+)-ratio in K 562 leukemia cells as revealed by X-ray microanalysis.

Changes of intracellular ionic homeostasis are believed to play a role in the cytostatic action of cis-DDP. It has been observed by means of X-ray microanalysis that cis-DDP did not alter the intracellular Na+/K(+)-ratio of K 562 leukemia cells during incubation periods which lasted shorter than the average doubling time of the cells of nearly 15 h. After 24 h the treated cells displayed at least two main populations in the distribution histogram of the Na+/K(+)-ratio. The results indicated that the passage of cis-DDP through the plasma membrane by itself did not change the monovalent electrolyte balance at the early stage of its action in K 562 cells.

Cell Survival↗
PubMed1990

[Prognostic significance of nuclear DNA content in highly malignant thyroid tumors].

The nuclear DNA content of tumour cells is correlated with the clinical outcome of a wide range of malignant disorders, among them thyroid neoplasia. The authors performed DNA determinations by means of the Feulgen cytofluorimetric method and demonstrate the connection between ploidy and biological aggressivity in cases of highly malignant thyroid tumours. The nuclear DNA content was measured in fresh surgical specimens from 53 patients suffering from malignancy, 13 of which proved pathohistologically to be highly malignant: 8 were anaplastic giant cell carcinomas, 3 squamous cell carcinomas and 2 were malignant lymphomas. 4 of the 8 giant cell carcinomas contained co-existent well-differentiated areas, namely follicular carcinomas in 3 patients and a papillary carcinoma in the 4th patient. 11 of the patients died of cancer, 9 within the 1st year. A different DNA distribution was found in the two survivors over a 10-year follow-up period. One of them showed a diploid cell population and the other facultative polyploidy, as opposed to the aneuploid pattern found in the 11 deceased patients. Both patterns confirm the correlation with a favourable outcome.

Adenocarcinoma↗