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Biomedical subjects

K Nagy

Publications and source records attributed to K Nagy.

At least 91 records · Page 5Linked to original sources

[Comparative in vitro dissolution studies of piroxicam suppositories using the basket, the paddle and the flow through methods].

The purpose of our work was the studying of the in vitro dissolution behavior of suppositories containing piroxicam as active ingredient with the Flow-through method comparing the results with the ones obtained by the conventional stirred vessel-USP Paddle and Basket methods. The results indicate that the Flow-through method seems to be useful for studying the dissolution process of suppositories containing piroxicam giving reproducible dissolution data. The Flow-through cell method gives faster in vitro dissolution rates for piroxicam than those with the USP Paddle method, probably caused by steeper concentration gradient at the vicinity of the suppositories as well as better ability to uniformly wet them. The USP Basket method was found to give substantially slower dissolution rates than the other two methods.

Kinetics↗

[Therapeutic problems in disseminated histiocytosis X].

The authors are dealing with the therapy problems of disseminated Langerhans cell histiocytosis on the basis of seven patients. In the treatment the combination of Vinblastine and Prednisolone was usually applied. The therapy was successful in four cases. The most significant prognostic factors were found to be the presence of organ dysfunction (mainly hepatic and pulmonary), the bone involvement and immunological parameters, respectively. Real therapy goals are stressed.

Female↗

Cyclic nucleotides and inositol trisphosphate activate different components of the receptor current in Limulus ventral nerve photoreceptors.

Receptor currents activated by short flashes were measured in ventral nerve photoreceptors of Limulus before and after injection of neomycin or phosphodiesterase (PDE). Neomycin inhibits the inositol cascade and PDE hydrolyses cyclic nucleotides. The effect of these substances was studied on the three current components, which were suggested to be activated by distinct transduction mechanisms. The second component of the current was selectively blocked by neomycin and the third component by PDE. The first component was inhibited by both substances. Thus, two transduction mechanisms for two current components could be unequivocally identified. Results support the previous assumption that light activates distinct mechanisms and transmitters in Limulus photoreceptors.

Adaptation, Physiological↗

Seventeen-year review of sexual and contraceptive behavior on a college campus.

OBJECTIVES: We reviewed current sexual and contraceptive behavior of college-age men and women and compared the findings with those of similar studies in 1974 and 1979. STUDY DESIGN: A randomly selected population questionnaire was provided to students registered in the spring 1991 semester. Of the 1921 survey forms mailed, 772 (40.2%) were returned. The CHIFIT test was used to determine representativeness of sample population to target population. RESULTS: Proportionately more women than men responded, although the age grouping and academic standing were consistent with the university population. Of the 772 responses, 84.2% were sexually active with a mean age at onset of 17.8 years. Half (50.3%) always used contraception with oral contraceptives as the first choice and condoms second. Sexually transmitted diseases were reported by 19.1%. More than one fourth (27.8%) had been tested for human immunodeficiency virus or acquired immunodeficiency syndrome. Fifteen percent (15.1%) reported being forced to have sex, and 50% of these incidents had occurred before age 19. CONCLUSIONS: On a comparison with findings in 1974 and 1979, more students had participated in sexual activity beginning at a younger age with slightly less use of contraception.

Contraception↗

Studies on the mechanism of complement-mediated inhibition of antibody binding to HIV gp41.

We have previously demonstrated that HIV envelope gp41 binding to specific antibodies decreases after preincubation of fluid-phase gp41 in normal human serum. This inhibition is proven to be mediated by the classical complement pathway. In this study recombinant gp41 (rgp41) and/or synthetic peptides were preadsorbed to solid phase, and then complement (normal human serum/heated human serum/purified Clq/heated Clq) and anti-gp41 antibodies were added either after each other or simultaneously, and the amounts of bound antibody, and deposited C3b, C4b and Clq were measured. Complement-dependent inhibition of antibody binding to solid-phase rgp41 was found, and Clq seems to be at least partially responsible for this phenomenon. Heating of Clq did not affect this process. Higher amounts of anti-gp41 antibodies significantly and dose-dependently enhanced C4b and C3b fixation to solid-phase rgp41. In the case of synthetic peptides corresponding to the immunodominant region of gp41, significant antibody binding to the solid-phase peptides was also detected, and pretreatment of peptides preadsorbed to solid phase with normal human serum almost totally abolished the antibody binding.

Amino Acid Sequence↗

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↗

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↗