Survivors' congress promotes cancer research.
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Foundations↗
Biomedical subjects
K Nagy
Publications and source records attributed to K Nagy.
[Changes in the frequency of childhood brain tumors in North-East Hungary].
Authors report about a seemingly increase of the number of pediatric brain tumors in Borsod county region North-East Hungary. In a retrospective study they conclude, that this phenomenon may to a great extent be artificial, that is, it may reflect the improvement of diagnostic possibilities, above all the new imaging modalities. At their Institution the pattern of brain tumors is similar to that reported in the literature. In addition a racial difference has been detected, since the gipsy population of this region seems to have lower incidence of pediatric brain tumor than the Hungarian majority.
Age Factors↗
Non-independent quantum bumps in Limulus ventral nerve photoreceptors--a new insight in the light transduction mechanism.
Single photon-induced transient currents, called quantum bumps were stimulated by short flashes in dark-adapted ventral nerve photoreceptors of Limulus. Flash intensities were set to activate 3 or more bumps. In most cases, current bumps were activated with a constant rate. The frequency of bump occurrence was between 9 and 17 Hz. Results show that consecutive bumps are not independent and that some of them are not activated by a photon. The periodic bump activation indicates a molecular mechanism which quantifies the transmitter release not only by a light quantum, but also by a late phase of the transduction cascade. A model is proposed, in which Ca2+ ions released from intracellular stores transiently block the further Ca2+ release by inositol trisphosphate in an all-or-none manner.
Animals↗
Three components in the light-induced current of the Limulus ventral photoreceptor.
1. Light-induced currents were measured in Limulus ventral nerve photoreceptors using a two-electrode voltage clamp. Three kinetically distinct components in the light-induced current could be distinguished by varying the light adaptation state of the photoreceptor and the intensity of the stimulus light. 2. The components could be partly separated by choosing appropriate stimulus intensities and dark adaptation time. Thus the properties of the components could be separately studied. The first component is the first to recover after a light adaptation, appears temporally first in the light-induced response, has the lowest activation threshold and is the smallest. The second component needs a longer time to recover after an adapting illumination and its kinetics differ from that of the other components. Applying a bright stimulus to a dark-adapted cell a third component can be observed late in the response. 3. The time to peak of the first and the third components depended on the stimulus intensity, but not on the dark adaptation time. The time to peak of the second component became shorter the longer the dark adaptation time. For a constant adaptation state the time to the maximum of component 2 was independent, but those of components 1 and 3 were dependent on the membrane voltage. 4. To exclude the possibility of the contribution of voltage-gated currents, light-activated currents were measured at clamp potentials more negative than -50 mV after adding 4-aminopyridine into the bath solution or injecting tetraethyl-ammonium chloride into the cell. The properties of the three components remained unchanged under these conditions. 5. The I-V curve of the first component was flat at negative membrane potentials and had a strong outward rectification at positive membrane potentials. The I-V curve of component 3 showed a negative resistance at potentials more negative than about -30 mV. In contrast, the I-V curve for the second component was always nearly linear. 6. No membrane potential was found where the light-induced current was zero. Instead, current traces close to the reversal potential showed a complex waveform indicating different reversal potentials for the three components. 7. The results indicate that the current components are caused by three different populations of light-sensitive channels. The different activations, deactivations and recovery kinetics of the components suggest that the three types of channels are activated by distinct intracellular transmitters.
4-Aminopyridine↗
[Familial cyclic neutropenia].
This rare disorder characterized by regular periodic oscillations in the number of peripheral neutrophils from normal to neutropenic levels. A case of a fourteen years old boy is presented who developed the disease at age of four years. Neutropenic periods appeared at intervals of 21 days and were associated with recurrent infections--gingivitis, stomatitis, conjunctivitis. The possible mechanism of impaired granulopoiesis and different therapeutic approaches are discussed.
Adolescent↗
Impaired translocation of protein kinase C activity in human non-insulin-dependent diabetes mellitus.
Calcium- and phospholipid-dependent protein kinase (protein kinase C; PKC) may be an important mediator in transduction of some of the cellular actions of insulin. We studied PKC activity in freshly isolated circulating mononuclear cells obtained from healthy subjects and patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM). The kinase activity was measured using a specific nonapeptide substrate, Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide. There was negligible calcium- and phospholipid-independent kinase activity in cytosolic and particulate fractions of cells from both control and diabetic subjects. Total (cytosolic and particulate) PKC activity of mononuclear cells from poorly controlled diabetic patients was significantly reduced compared with controls; this reduction was mainly due to a decrease in the cytosolic kinase activity. Tumor-promoting phorbol ester (TPA, 0.1 mumol/L) induced translocation of PKC activity in control cells; in contrast, this subcellular redistribution was not observed in cells from a majority of poorly controlled diabetic subjects. Increased calcium influx into the cells caused by the calcium ionophore A23187-triggered translocation of PKC activity in control cells, while it was ineffective in cells from poorly controlled diabetic patients. Cells from well-controlled diabetic patients demonstrated TPA-induced translocation of the PKC activity approaching that of control cells. The total PKC activity in cells from patients with good glycemic control was normal. Impaired activation of PKC is thus associated with the insulin resistance found in patients with poorly controlled NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Glucose↗
Biophysical processes in invertebrate photoreceptors: recent progress and a critical overview based on Limulus photoreceptors.
Limulus ventral nerve photoreceptor, a classical preparation for the study the phototransduction in invertebrate eyes, seems to have a very complex mechanism to transform light energy into a physiological signal. Although the main function of the photoreceptor is to change the membrane conductance according to the illumination, the cell has voltage-activated conductances as well. The voltage-gated conductances are matched to the light-activated ones in the sense that they make the function of the cell more efficient. The complex mechanism of phototransduction and the presence of four different voltage-gated conductance in Limulus ventral nerve photoreceptors indicate that these cells are far less differentiated than the photoreceptor cells of vertebrates. Indications accumulated in recent years support the view that the ventral photoreceptor of Limulus has different light-activated macroscopic current components, ion channels and terminal transmitters. After conclusions from macroscopic current measurements (Payne, 1986; Payne et al. 1986 a, b), direct evidence was presented by single-channel (Nagy & Stieve, 1990 a, b; Nagy, 1990 a, b) and macroscopic current measurements (Deckert et al. 1991 a, b) for three different light-activated conductances. It has been shown that two of these conductances are stimulated by two different excitation mechanisms. The two mechanisms, having different kinetics, release probably two different transmitters. One of them might be the cGMP (Johnson et al. 1986), the other one the calcium ion (Payne et al. 1986 a, b). However, the biochemical processes which link the rhodopsin molecules and the ion channels are not known. The unknown chemical details of the phototransduction result in a delay for the mathematical description of the biophysical mechanisms. More biochemical details are known about the adaptation mechanism. It was found that inositol 1,4,5-trisphosphate is a messenger for the release of calcium ions from the intracellular stores and that calcium ions are the messengers for adaptation (Payne et al. 1986 b; Payne & Fein, 1987). Concerning the mechanism of calcium release, it was revealed that a negative feedback acts on the enzyme cascade to regulate the internal calcium level and to protect the stores against complete emptying (Payne et al. 1988, 1990). Calcium ions also play an important role in the excitation mechanism. (a) In [Ca2+]i-depleted cells the light-induced current was increased after intracellular Ca2+ injection, suggesting that calcium is necessary for the transduction mechanism (Bolsover & Brown, 1985).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The complement system in HIV disease.
Different aspects of the relationship between the HIV infection and the complement system were studied. 1. No significant differences were found between seronegative controls, asymptomatic, and symptomatic (ARC, AIDS) HIV-seropositive patients in the plasma levels of complement components C4, Bf, and C3. 2. Using sensitive ELISA assays, a significant increase was observed in the levels of protein-protein complexes which are formed at the activation of the classical (C1r-C1s-C1-INH) and alternative (C3b-Bb-P) pathways, indicating that both complement pathways are activated in the HIV disease. No significant differences were found, however, in the levels of these complexes between the groups of asymptomatic and symptomatic HIV-infected patients. 3. Artificial immune complexes of synthetic peptides representing some immunodominant epitopes of HIV envelope (gp120, and gp41) proteins, and human polyclonal anti-HIV IgG were found to weakly activate both the classical and alternative complement pathways. 4. An elevated percentage of the lymphocytes carrying a complement activation fragment, C3d, was detected in the blood of HIV seropositive patients as compared to the seronegative controls. No significant positive correlation was found between the percentage of these cells and that of any T cell subsets tested.
Complement Activation↗
[Comparison of sonography and arthrography in the examination of cysts around the knee].
Authors used in 1988 simultaneously sonography and arthrography during the treatment of 10 patients admitted with the diagnosis of cyst or tumour around the knee. The experiences with the comparison of the 2 methods are summarized. As this use of the method is first described in this country, before the description of their own material the relevant available foreign literature is also discussed. It is stated that in the differential diagnosis of the cysts around the knee the 2 methods may give good complementary informations. It is stressed that if a choice is possible, the sonography is the method of choice, being exempt from X-rays, noninvasive, not causing pain and cheaper.
Adult↗
Measurement of the inflammatory activity by the help of serum acute-phase proteins in juvenile chronic arthritis.
We measured the level of serum haptoglobin, transferrin, alfa-I antitrypsin, orosomucoid, beta-2-microglobulin, ferritin in the case of 30 children (aged 11-16 years) with juvenile chronic arthritis. We divided the patients into two groups. In the first group there were 15 patients with active disease under continuous treatment and in clinical remission (We 20 mm/hour). In the second group there were 15 patients without active disease and they were not given continuous treatment for two Years. These groups were studied, by a control one. If we measure more phase-proteins together, they are suitable for the demonstration of the inflammatory activity in juvenile chronic arthritis. We made a points system for the evaluation of activity.
Acute-Phase Proteins↗
Peripheral blood lymphocyte subpopulations in children with juvenile chronic arthritis.
Peripheral blood lymphocyte subset levels were analyzed in 28 patients with active, polyarticular, juvenile chronic arthritis and in 12 healthy control children. The patients with a similar treatment were divided into two groups, at the beginning of disease and after five years course. Ten children with juvenile chronic arthritis were treated by glucocorticosteroid. After five years the percentage of active T cells, T suppressor cells and active (total T cells ratio were significantly elevated and there was a same decrease in the T4/T8 ratio. Glucocorticosteroid increased proportion of active T cells but it did not change the percentage of other lymphocyte subsets. It is concluded that during the course of disease a drug-induced or spontaneous effect appears which corrects the initial immunological disturbances.
Adolescent↗
[Isolation of human immunodeficiency virus from Hungarian AIDS and ARC patients].
Human immunodeficiency virus infected persons are usually identified by indirect methods, detecting viral-specific antibodies. Helping the early diagnosis of HIV infection there is a need to detect virus or viral specific antigens directly. Virus isolation have been attempted from separated lymphocytes of HIV infected five homosexual male patients and one transfusion recipient. Three patients had AIDS, three belonged to the ARC group at the time of the examination. In 3 out of 6 lymphocyte cultures cocultivated with normal donor lymphocytes, virus antigens and virus replications had been detected within ten days of culture. The amount of HIV antigen p24 ranged between 0.5----2.0 ng/ml during the first two weeks of cocultivation. Permanent human lymphoid and monocyte/macrophage cell lines have been infected by the viruses isolated from the primer lymphocyte cocultures. Productive infection could be initiated in Jurkat tat-III and U937 cells, while infection of Jurkat and HUT 78 cell lines was transient. Results indicate, that HIVs could be isolated from infected Hungarian patients with various stages of AIDS and one isolate--termed HIV-1FB918--actively replicates in human permanent cell lines.
AIDS-Related Complex↗
No evidence for human T-cell leukemia virus type I or human T-cell leukemia virus type II infection in patients with multiple sclerosis.
The involvement of human T-cell leukemia viruses (HTLVs) in the pathogenesis of 18 Hungarian patients with multiple sclerosis was investigated. No antibody to HTLVs could be detected in any of the patients. Furthermore, using polymerase chain reaction under highly sensitive conditions, neither HTLV-I DNA nor HTLV-II DNA could be noted in peripheral blood lymphocytes of the patients. Our data do not support a causal association of HTLV-I or HTLV-II with multiple sclerosis.
Adult↗
Serum levels and catabolism of 3'-azido-3'-deoxythymidine in vivo measured using a specific radioimmunoassay.
The thymidine analogue 3'-azido-3'-deoxythymidine is an effective inhibitor of HIV replication in vitro and is used in the treatment of acquired immunodeficiency syndrome. We report here upon a rapid sensitive radioimmunoassay for the detection of azidothymidine in serum or plasma. The assay is simple to perform and levels as low as 1 ng azidothymidine/ml can be detected. The assay is specific for azidothymidine and shows almost no cross-reaction with closely related nucleoside analogues or with naturally occurring nucleosides. Using this radioimmunoassay we were able to measure the azidothymidine levels in the serum of monkeys and acquired immunodeficiency syndrome patients treated with AZT. Individual variation in the peak serum level and clearance rate of azidothymidine were seen, which emphasizes the need to tailor the dose to the individual.
Acquired Immunodeficiency Syndrome↗
Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera.
The kinetics of appearance and specificity of HIV-1 neutralizing antibodies was studied in four individuals. HIV-1 was isolated during symptomatic primary HIV-1 infection and repeatedly thereafter, and tested against autologous sera collected in parallel. Our patients developed isolate-specific low-titer neutralizing antibodies within 2-4 weeks, and the titers to the first isolates increased with time. We documented the emergence of virus variants with reduced sensitivity to neutralization by autologous, but not heterologous, sera in three patients. These virus variants were not, however, resistant to neutralization per se, since they were readily neutralized by the positive control serum. Our patients did not develop antibodies capable of neutralizing the new virus variants during the observation period. This suggests either a failure of the immune system to respond to the new virus variants or a mechanism by which the virus evades detection by the immune system. The emergence of neutralization-resistant virus variants was not directly correlated with disease progression since two patients have remained asymptomatic after the emergence of such virus variants. It is, however, likely that the emergence of virus variants which the patient fails to neutralize in the long run contributes to disease progression.
Acquired Immunodeficiency Syndrome↗
Insulin antagonistic effects of insulin receptor antibodies on plasma membrane (Ca2+ + Mg2+) ATPase activity: a possible etiology of type B insulin resistance.
The regulatory effect of insulin on plasma membrane (Ca2+ + Mg2+)ATPase activity in target tissues for insulin was proposed to be of importance in mediating the hormone's cellular action. Consequently, polyclonal insulin receptor antibodies from patients with type B insulin resistance (B7 and B10) were used as probes to further explore a possible role for this ATPase in insulin action. The antibodies B7 and B10 obtained during the active phase of the disease manifested insulinomimetic actions in rat renal cortical basolateral membranes by displacing [125I]insulin bound to the membranes and stimulating the tyrosine kinase activity of solubilized insulin receptors in a dose-dependent manner. In contrast, these antibodies had insulin antagonistic effects on the membrane (Ca2+ + Mg2+)ATPase activity. While insulin stimulated, both antibodies inhibited the ATPase basal activity in a dose-dependent manner. Furthermore, the stimulatory effect of insulin on the ATPase was completely abolished by the antibodies. Immunoglobulin fractions obtained from patient B10 in the clinically inactive phase of the disease and from pooled normal human sera did not affect basal or insulin-stimulated ATPase activity. The effects of insulin receptor antibodies on basal and insulin-stimulated (Ca2+ + Mg2+)ATPase activities were specific. The receptor antibody did not affect PTH-stimulated (Ca2+ + Mg2+) ATPase activity, nor did it affect other kidney basolateral membrane ATPase basal activities. The data reveal that insulin receptor antibodies have a direct regulatory effect on the plasma membrane (Ca2+ + Mg2+) ATPase. We suggest that the insulin antagonistic effects of the insulin receptor antibodies on the ATPase might explain in part the impaired insulin action in type B insulin resistance.
Animals↗
High-fat feeding induces tissue-specific alteration in proportion of activated insulin receptors in rats.
High dietary fat intake causes glucose intolerance and insulin resistance in man and in laboratory rats. We studied possible mechanisms of this insulin resistance in rat kidney, muscle and liver. In high-fat fed rats the body weight, plasma insulin concentration, plasma glucose levels, and serum triglyceride concentration were significantly higher than in the control rats. 125I-insulin binding to kidney basolateral membrane insulin receptors from high-fat fed rats was lower than in control rats. Basal as well as insulin-stimulated tyrosine kinase activity per insulin receptor was higher in the high-fat fed group, accompanied by increased autophosphorylation of the beta-subunit of the receptor and higher proportion of tyrosine-phosphorylated insulin receptors. In contrast, both in the skeletal muscle and the liver the insulin-stimulated tyrosine kinase activity per insulin receptor was significantly lower in high-fat fed animals, accompanied by diminished autophosphorylation of the beta-subunit of the receptor and lower proportion of tyrosine-phosphorylated receptors. Our results indicate tissue-specific alterations in transmembrane signaling induced by high-fat feeding in target tissues for insulin which in turn might contribute to the observed insulin resistance.
Animals↗
Abnormal insulin receptor tyrosine kinase activity in kidney basolateral membranes from non-insulin-dependent diabetic rats.
Neonatal rats that receive injections of streptozotocin develop insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). Insulin resistance precedes development of overt diabetes, and some insulin bioeffects are known to be impaired at the postreceptor level in several target tissues of this rat model. We studied a possible contribution of altered insulin receptor function to the impaired insulin action in these animals. Activity of the insulin-sensitive tyrosine kinase of receptors from kidney cortical basolateral membranes (BLMs) obtained from these nonobese, normoinsulinemic, insulin-resistant rats was examined at the age of 5 weeks (before overt hyperglycemia developed) and at 10 weeks (after NIDDM was fully manifested). In experimental animals, at both 5 and 10 weeks, binding of insulin labeled with iodine 125 to crude kidney BLM was higher than in their control littermates. However, no such difference was found with insulin binding to purified insulin receptors from BLM. The insulin receptor, tyrosine kinase activity (TKA), to an exogenous substrate was higher in diabetic tissue both at basal condition and after insulin stimulation at both 5 and 10 weeks of age. Autophosphorylation of the beta-subunit of the insulin receptor and the proportion of tyrosine-phosphorylated ("active") insulin receptors from BLM was also higher in diabetic rats. There was an age-related increase in the receptor TKA between 5 and 10 weeks in both diabetic and control animals. A 24-hour fast normalized insulin binding and nearly abolished the difference in TKA of the BLM receptors from 5-week-old insulin-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗