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Biomedical subjects

K Nagy

Publications and source records attributed to K Nagy.

At least 109 records · Page 6Linked to original sources

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↗

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 decrease in the T4/T8 ratio. Glucocorticosteroids increased the proportion of active T cells but did not change the percentage of other lymphocyte subsets. It is concluded that during the course of disease a drug-induced or spontaneous process appears which corrects the initial immunological disturbance.

Adolescent↗

[False positive results of HIV virus tests in patients undergoing chronic hemodialysis].

The sera of 173 haemodialysis patients treated in two dialysis centers in Hungary were tested for the presence of HIV (HTLV III/LAV) antibodies. Four different commercial enzyme immunoassay (EIA) kits and two types (CEM/LAV, and H9/HTLV III) of indirect immunofluorescence assay (IFA) were used. The Western blot technique was applied as confirmatory test in the study. No confirmed positive results were found in any of the cases. However, in 15 patients (8.7%) false positive (not confirmable by the Western blot assay) results were obtained in at least one but mostly in all of the three type 1 EIA kits (ORGANON, ELECTRONUCLEONICS, SORIN) applied. In 4 patients, the IFA assay also gave false positive results which could be repeated in sequential samples taken from the same patients. Increased reactivity in the control plate (coated with a concentrate of cellular material shed by uninfected H9 cell line) of the SORIN kit was found only in a few false positive samples and no fluorescence with the uninfected H9 or CEM cells was observed in any of the sera showing a false positive IFA. These results indicate that the false positive anti-HIV results frequently observable in haemodialysis patients are not simply the consequence of the presence of antibodies reacting with the uninfected H9 and/or CEM cells but they are most probably due to antibodies against antigens expressed on these cells only after infection with the human immunodeficiency virus.

False Positive Reactions↗

Iron-induced lipid peroxidation and inhibition of dopamine synthesis in striatum synaptosomes.

Crude striatum synaptosomes (P2 fraction) from Fischer 344 female rats were incubated in the presence of ADP-chelated Fe3 (0.5-50 microM) and ascorbate (250 microM). Intrasynaptosomal conversion of tyrosine to dopamine (DA) was measured by 14CO2 evolution from L-[1-14C]tyrosine in the absence of added cofactors and DOPA decarboxylase. Malondialdehyde (MDA) was measured as an index of lipid peroxidation. A concentration-dependent inhibition of DA synthesis by ADP-Fe3./ascorbate was found with 50% inhibition occurring at 2.5 microM Fe3 concentration. This was accompanied by marked accumulation of MDA. Ascorbate or ADP alone did not affect DA synthesis and ADP-Fe3 in the absence of exogenous ascorbate was effective only above 25 microM. Exogenously added MDA did not inhibit DA synthesis. Purified synaptosomes were isolated from peroxidized and control P2 actions using sucrose gradients. Membrane microviscosity of the purified synaptosomes was assessed by nitroxyl spin labels of stearic acid using electron paramagnetic resonance techniques. There was a significant increase in membrane microviscosity as a result of ADP-Fe3./ascorbate induced peroxidation. Maleimide nitroxide spin-label binding to protein sulfhydryls was significantly modified by peroxidation of striatum synaptosomes. The weakly immobilized component of the sulfhydryl spin-label (w) was drastically decreased whereas the strongly immobilized component (s) was modified less, thus leading to a marked reduction of w/s ratio. The exposure of striatum synaptosomes to the peroxidizing system resulted in a significant increase in total iron and in a 25% decrease in protein sulfhydryl content. It is concluded that iron-induced damage to the DA synthetic system is mediated by alterations of the structural properties of nerve ending membranes.

Adenosine Diphosphate↗

Different types of false positive anti-HIV reactions in patients on haemodialysis.

Serum samples of 589 haemodialysis patients were screened for HIV antibody by ELISA methods. Of these, 36 samples were found to be repeatedly reactive. None of the 36, however, could be confirmed by competitive enzyme immunoassays and Western blot; therefore, they were considered to be false positive. The sera could be divided in two groups. The sera of Group 1 were designated as the usual type of false positivity, caused most probably by anti-lymphocyte antibodies. In 19 sera, however, a special type of false positivity was found. These sera reacted strongly with the plates coated with the supernatants of HIV-infected cells but not with those of uninfected H9 cells. Three and two sera showed, respectively, positive immunofluorescence reaction with the HIV-infected, but not with the uninfected, H9 and CEM cells. Reactivity to HIV-infected H9 cells could be adsorbed from a part of these samples with lesser amounts of HIV-infected than uninfected H9 cells. This special type of false positivity was observed frequently (7/65) in patients who rejected a kidney graft. These findings suggest that this type of anti-HIV false positivity is due to antibodies reacting with cellular antigens present in HIV-infected but not in uninfected lymphocytes. Their appearance seems to be associated with the immunological activation occurring at graft rejection.

Blotting, Western↗

Subacute toxicological examination of Dithane M-45.

A subacute toxicological study of the effects of the ethylene-bisdithiocarbamate-containing fungicide Dithane M-45 (80% mancozeb) was carried out in male Wistar rats. The rats were given Dithane mixed in the feed at doses of 0, 10, 50, 75, 113, 169, 253 or 379 mg/kg body weight for 12 wk. One-third of the rats given 379 mg Dithane/kg body weight died, and doses of greater than or equal to 169 mg/kg decreased the growth of the rats as well as the nutrient utilization. The relative weights of the liver and thyroid were significantly increased in rats given greater than or equal to 75 mg Dithane/kg body weight, and those of the kidneys, adrenals and testes were significantly increased in the two highest dose groups. The serum cholesterol level was increased significantly in groups given greater than or equal to 75 mg/kg, and doses of 113, 169 or 253 mg/kg caused the elevation of the triglyceride content of the liver. The two highest doses of Dithane decreased the detoxicating capacity of the liver. The function of the thyroids was impaired even by very small doses of Dithane: at a dose of 10 mg/kg body weight the quantity of iodine stored in the thyroids was decreased by 20%. At doses of greater than or equal to 50 mg/kg statistically significant decreases in thyroid iodine content were observed. Histological examination of the thyroids showed dose-dependent hyperplasia in rats treated with Dithane.

Animals↗

Examination of the interaction of decis and dithane in rats.

Acute (LD50) and short-term (14 days) toxicological examinations were performed in animal experiments on the interaction of a synthetic pyrethroid Decis 2,5 EC (25 g deltamethrin/l) and of ethylene-bisdithiocarbamate/Dithane M-45 (80% mancozeb), using a 1:5 deltamethrin/mancozeb mixture. LD50 value of the mixture was similar to that of the more toxic Decis. In the short-term examination, some pathologically high AST and ALT values were observed in the treated groups and the deltamethrin content of fatty tissue samples increased parallel with the increase of Decis consumption. The chymotrypsin and lipase activities in the small intestinal mucosa and gamma-GT and LAP activities in the content of the bowels were reduced in several treated groups. The administration of Dithane in a dose in accordance with 20% of the LD50 value (3125 mg/kg b.m.) proved to be more toxic than expected and caused the death of the animals.

Adipose Tissue↗

Conditional open and delay time histograms of sodium channels.

Currents through single sodium channels were recorded in neuroblastoma cells. Open time histograms were constructed from openings which appeared between 2.0 and 5.0 ms after the onset of the depolarization. Histograms constructed from openings which were not preceded by other openings showed a maximum at t greater than 0 in contrast to those, which were preceded by other openings. Time constants of delay time histograms fitted by the sum of two exponentials were different for the first, second and third records of runs. The results support the view that sodium channels have multiple open and closed states and the transition probabilities among the states depend on local conditions of the membrane.

Animals↗