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I Zs-Nagy

Publications and source records attributed to I Zs-Nagy.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1989

The lack of age-pigments and the alterations in intracellular monovalent electrolytes in spontaneously hypertensive, stroke-prone (SHRsp) rats as revealed by electron microscopy and X-ray microanalysis.

Male, spontaneously hypertensive, stroke-prone (SHRsp) rats established by Okamoto et al. (1974) were studied. About 80% of the males of this strain have a particularly short life span (33-41 weeks); they display a considerable hypertension (above 220 mmHg) and a tendency for plurifocal brain strokes. Hypertension and strokes can be provoked in an accelerated and synchronized fashion by supplementing 1% NaCl into their drinking water. Symptoms of the appearance of brain strokes can be judged from characteristic signs of motor disorders, and can be established also by pathohistology. Since hypertension and arteriosclerosis are frequently involved in aging, the question we intended to answer was whether these animals may represent a model of the normal aging process or not. Two approaches are described: (1) Accumulation of lipofuscin granules in their brain, liver and myocardium was followed by transmission electron microscopy before and after the appearance of strokes. It has been established that these tissues do not show any typical accumulation of lipofuscin granules, although submicroscopic signs of an enhanced damage of cell organelles (especially of mitochondria in liver and brain cells, but not in myocardium) were encountered. (2) The intracellular monovalent composition in the brain and liver was measured by using bulk-specimen X-ray microanalysis. The intracellular Na-content (mEq/kg water) was significantly higher (170-200%) in both the brain and liver cells, whereas the K-content increased only moderately (118-130%). The results suggest that although the SHRsp rats do not represent a direct model for the normal aging process from the point of view of lipofuscin accumulation, the shifts of the monovalent electrolyte contents in the brain and liver cells observed already in the youngest ages, are similar to those observed in aged normal rats. The theoretical consequences of such a conclusion are discussed.

Aging↗
PubMed1989

Gerontopsychological studies using NAI ('Nürnberger Alters-Inventar') on patients with organic psychosyndrome (DSM III, Category 1) treated with centrophenoxine in a double blind, comparative, randomized clinical trial.

A double blind clinical trial was performed on 50 persons (25 men, 25 women) over the age 60 (average age: 77 years). They suffered from dementias of medium level (DSM III, Category 1, ICD No. 299), and had been residents in an old age home longer than 3 months at the start of the trial. The patients were treated first for 2 weeks by placebo tablets and their initial performance was recorded during this period by using the Nuremberg Gerontopsychological Inventory (NAI). This was then followed by a treatment for 8 weeks with the nootropic drug, centrophenoxine (CPH), the dose of which was 2 g/day distributed in 2 x 2 tablets of Helfergin500 (Promonta, Hamburg, FRG), or with placebo tablets of identical size, then the NAI test was repeated again. Verum or placebo treatment was selected randomly and the code was revealed only after having elaborated all the results of the trial. During the treatment period four drop-outs occurred for intercurrent diseases. Evaluation was based on a semi-quantitative, intra-individual comparison of the performance before and after treatment. The results obtained suggest that CPH treatment may be useful in dementias of medium level in quite old groups of patients, since 48% of the verum group displayed improvements in the memory functions against 28% of the placebo group. CPH seems to be a useful and harmless drug in the treatment and most probably also in prevention of the dementias.

Aged↗
PubMed1989

Effect of centrophenoxine and BCE-001 treatment on lateral diffusion of proteins in the hepatocyte plasma membrane as revealed by fluorescence recovery after photobleaching in rat liver smears.

The average lateral diffusion coefficient of proteins (D) in the cell membrane of hepatocytes has been measured in liver smears by fluorescence recovery after photobleaching (FRAP), based on the so-called peroxide-induced autofluorescence (PIAF) deriving from the oxidation of riboflavin bound to membrane proteins. It has been previously shown that D displays a significant negative linear age correlation. The in vivo effects of two drugs were tested on this parameter. Young (2.7 months) and old (24-26 months) male rats received centrophenoxine (CPH) or a new drug (BCE-001) by either intraperitoneal (i.p.) injection or per os through a gastric tube for 26 to 42 days. D was measured on a double-blind basis in the hepatocyte plasma membrane of treated and control groups. The CPH and BCE-001 treatments did not affect the value of D in the young rats. However, the latter drug increased their growth rate. An increase of D in old animals was induced by treatment with either drug. When the drug effects in old rats were compared, BCE-001 proved to be more efficient than CPH, and at the same time was able to significantly retard the age-dependent loss of body weight characteristic of these animals at the age of approximately 2 years. Our results are in good accord with the predictions of the membrane hypothesis of aging as regards the role of properly placed OH. free radical scavengers in the improvement of membrane and overall cell function.

Aging↗
PubMed1989

Age-dependence of the lateral mobility of proteins in the plasma membrane of hepatocytes of C57BL/6 mice: FRAP studies on liver smears.

Protein lateral diffusion in hepatocyte membranes was measured in 23 male and 16 female C57BL/6 mice in four groups of age 5 to 32 months by means of fluorescence recovery after photobleaching (FRAP). The peroxide-induced autofluorescence (PIAF) in H2O2 treated liver smears is due to the oxidation of flavins bound uniformly to all proteins of the cell membrane, i.e., an average lateral diffusion constant (D) of those proteins can be measured. D showed a negative linear age-correlation in both sexes: D male = (2.81 - 0.016X)10(-10), and D female = (2.67 - 0.020X)10(-10) cm2/sec, (r greater than 0.94), where X is the age in months. Sex differences are significant (p less than .001) in the intercept. Fractional recovery did not prove to be age-dependent; it was, on average, 91% in males and 100% in females. The findings agree well with the previously obtained data on Fischer 344 and Wistar rats, and strengthen the gerontological relevance of D.

Aging↗
PubMed1989

A review on the use of bulk specimen X-ray microanalysis in cancer research.

The freeze-fracture, freeze-drying (FFFD) method of biological bulk specimen preparation combined with quantitative X-ray microanalysis is suitable for the measurement of intracellular concentrations of biologically relevant elements in human biopsy or experimental animal materials. Especially useful information can be obtained regarding the intracellular Na+/K+ ratios being independent of the actual (and unknown) water content of the cytoplasm. The sustained increase of this ratio indicates a sustained depolarization of the cell membrane. These data are of importance from the point of view of the membrane hypothesis of mitogenesis (MHM). It has been revealed that the distribution histograms of the intracellular Na+/K+ ratio display a very significant broadening and an increase of the average values in human urogenital, thyroid and laryngeal tumors, as well as in experimentally induced cell proliferation models. Although MHM has been claimed to be invalid on the basis of some atomic absorption measurements of the intracellular monovalent ion concentrations as well as of some in vitro results obtained with amiloride, this review paper demonstrates that MHM may still be a valid hypothesis for the explanation of mitotic regulation.

Cell Transformation, Neoplastic↗
PubMed1988

Possibilities and limitations of the smearing technique for cellular studies in compact tissues: a transmission electron microscopic analysis of liver smears.

During the last decade a sophisticated biophysical technique called fluorescence recovery after photobleaching (FRAP) has become available for the measurement of lateral diffusion constants of lipids and proteins in the cell membrane. The information obtainable by this method is of great importance; however, the applicability of this method is seriously hindered by the fact that it has been elaborated mostly for isolated, individual cells. On the other hand, the use of freshly prepared cells from compact tissues for such studies is highly desirable. Therefore, a special smearing method was devised (using liver cells) for this purpose. The present paper describes (i) the method of standardization of the smearing technique, (ii) the ultrastructural features of the liver cells when studying the liver smears by means of transmission electron microscopy. The possibilities and limitations of this method are discussed. According to the observations, under well-defined conditions the structural integrity of hepatocytes is maintained in the liver smears to such an extent that they are suitable for FRAP experiments.

Animals↗
PubMed1988

Dysdifferentiation hypothesis of aging and cancer: a comparison with the membrane hypothesis of aging.

Our laboratories have been testing the basic concept that the age-dependent deterioration of the molecular components of living systems may be due in part to the biochemical effects of active oxygen species. The dysdifferentiation hypothesis of aging and cancer (DHAC) as well as the membrane hypothesis of aging (MHA) are discussed and compared to each other. These two hypotheses consider cellular mechanisms through which free radical-induced alterations may lead to the aging process. DHAC emphasizes the importance of the instability of the differentiated state of cells and how active oxygen species may interact with the genetic apparatus of cells, leading to improper gene regulation. The evidence supporting this hypothesis includes an age-dependent increase in the expression of specific genes that normally are expected to be repressed. Such evidence now includes the c-myc oncogene as well as an age-dependent decrease in the average methylation level of the entire genome in liver tissue of mice. The central concept of DHAC is that aging is a result of gene regulatory instability and that lifespan is governed by mechanisms acting to stabilize proper gene regulation. MHA is based on the concept that all cellular components are exposed to free-radical attacks, and that the damaging efficiency of the radicals is density-dependent. Compact structures like membranes are consequently more susceptible to damage than cytosolic components. In addition, the cell plasma membrane is exposed to another damaging effect called residual heat damage, which is due to the depolarization-induced discharge of the membrane during the action potential. MHA predicts that a key process of normal differentiation as well as aging is a continuous, age-dependent loss of the passive permeability of the cell membrane for potassium and probably also for water. This is due to a constant difference between the rates of damage and replacement of the membrane components and results in a gradual dehydration of the intracellular mass from the embryonic state to the aging state. The increasing intracellular density will eventually become rate-limiting for many different cellular functions, resulting in the cessation of growth and the beginning of aging. MHA also predicts an overall decrease of gene expression and protein turnover rate during aging. Pharmacological interventions on the cell membrane have supported the validity of MHA and have indicated specific mechanisms of how aging and dysdifferentiation may occur.

Aging↗
PubMed1988

Effect of enzymic (collagenase) harvesting on the intracellular Na+/K+ ratio of Swiss/3T3 cells as revealed by X-ray microanalysis.

Swiss/3T3 cell cultures were harvested with 0.05% collagenase and after centrifugation the pellet was prepared by the freeze-fracture/freeze-drying (FFFD) method for bulk-specimen X-ray microanalysis. Time-dependent variations in the intracellular monovalent elemental concentrations (Na+, K+ and Cl-) as well as of the Na+/K+ ratio were followed for 120 min subsequent to harvesting. The quantitative measurements revealed a very considerable increase in the intracellular Na+ and Cl- accompanied by a decrease in the K+ concentration as soon as 5 min after harvesting. The Na+/K+ ratio had increased by this time to about 1.5 on average. These changes indicate a sustained depolarization of the cell membrane. During the first 60 min this depolarization tended to normalize as demonstrated by an exponential decrease in the intracellular Na+ and Cl- and an increase in the K+ content involving a decrease in the Na+/K+ ratio. The total intracellular monovalent ion concentration remained almost constant during this post-harvesting period. These results suggest that harvesting represents a serious depolarizing stimulus to the cells, the consequences of which are restored only after 1-2h. These alterations should be taken into consideration during various experimental designs when using anchorage-dependent cell cultures.

Animals↗
PubMed1987

Age-dependent changes in the osmotic behavior of rat brain and liver.

Osmotic potential of liver and brain tissue has been determined by measuring swelling or shrinkage of the tissues in anoxic Ringer solution the osmotic concentration of which was rendered hypo- or hyperosmotic by dilution or addition of polyethylene glycol (PEG 6000), respectively. The percentages of volume change were fitted to an exponential equation permitting the calculation of the initial speed of volume change. The age-dependent increase of the intracellular dry mass content was also taken into consideration. It has been established that initial velocity of the volume change displays an age-dependent decline in all kinds of media tested; however, the slope of this decrease is steeper in the diluted Ringer solution than in the other ones. Calculations show that the colloid osmotic pressure (mmHg) of the intracellular mass decreases between 1 and 26 months of age from 810 to 596 and from 2,477 to 904 in the brain and liver, respectively. The results may be interpreted as consequences of a decreased colloid dispersity which may be related to an oxygen free radical induced intermolecular cross-linking.

Aging↗