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Biomedical subjects

K Nagy

Publications and source records attributed to K Nagy.

At least 73 records · Page 4Linked to original sources

Interferon-alpha in childhood haematological malignancies.

The application of cytostatics has brought about a breakthrough in the treatment of childhood haematological malignancies in the past 20 years. Chemotherapy appears to be least successful in the rare, low and very high mitotic index diseases, which often have an enormous tumour-burden. The suitability of chemotherapy in minimal residual leukaemia is also of some doubt. In these situations a 'conservative' treatment may be more appropriate. Because interferon-alpha has a distinct mechanism of action, and a broad-spectrum haematopoietic inhibitory activity, it is relatively nontoxic and noncancerogenic, and it may have a role in the treatment of malignant haematological disorders, either as a mono- or combination therapy. The exact indications and dosages for interferon in childhood malignancies are far from clear. Up to now, it has proved to be most efficacious in small tumour masses, providing a theoretical basis for application in minimal residual disease. Controlled clinical data, however, are not yet available. It remains to be determined whether or not interferon can be added to current chemotherapy protocols without a significant reduction of dose. Hopefully, a deeper understanding of the activities of interferon will allow us to plan better trials with combination treatments.

Antineoplastic Agents↗

[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↗

Current components stimulated by different G-proteins in Limulus ventral photoreceptor.

The components of the light-activated current in ventral photoreceptor of Limulus have different physical and pharmacological properties, indicating the operation of different transduction pathways. We investigated whether these pathways are activated by different G-proteins. An antiserum, directed against the C-terminal sequence QLNLKEYNLV of the alpha subunit of the Gq-protein, which is present in squid photoreceptor, was injected into the ventral photoreceptor of Limulus. This Gq-alpha mediates the light-dependent activation of PLC. Injections of the antibody into the photoreceptor blocked the second component of the light-evoked current in Limulus ventral photoreceptor, but the other components could still be activated. The results support our earlier hypothesis that the transduction pathways of the current components are selectively activated by different G-proteins.

Amino Acid Sequence↗

A new method: double Thiry-Vella fistulas in rats to compare the effects of small and large intestinal stimulation on behaviour.

A new method for comparing the effects of small and large intestinal mechanical stimulation was developed. Isolated intestinal loops were created by the Thiry-Vella method from the lower duodenal--upper jejunal, and from the upper colonic portion of the gut, respectively. This preparation allows parallel evaluation of stimulation effects and affects from both the small and the large intestine of the same animal. A balloon could be inserted into the isolated loops before each experimental session and removed afterward. Behavioral thresholds to changes in the volume of the gut were recorded and compared in the two loops. No essential differences between the two portions of the intestinal tract were detected by this method.

Animals↗

Involvement of Fenton reaction products in differentiation induction of K562 human leukemia cells.

ADP-Fe2+ (or ATP-Fe2+) complex and H2O2, components of the Fenton reaction, were added to K562 cells, then cultured for 96 h. Ara-C-induced differentiation served as a basis for comparison. Cell numbers, viability, benzidine staining, thymidine incorporation, and cell-cycle distribution by means of flow cytometry were determined. The Fenton reagents reduced the growth rate and thymidine incorporation of leukemic cells in a dose-dependent manner as regards the added H2O2 (from 0.01 to 1.0 mM), accompanied by an accumulation of hemoglobin in them. Differentiation of the cells was accompanied by considerable changes in total SOD and catalase activities. Ara-C caused an increase of SOD to 366%, and of catalase to 235%, while the complete Fenton reaction resulted in SOD increase to 705% and catalase decrease to 38% of the untreated control cultures. These shifts in enzyme inductions suggest the existence of a higher H2O2 flux in the differentiating cells. The results are consistent with the assumption that products of the Fenton reaction, among them OH. radicals deriving from H2O2 by heterolysis, may play a causal role in cell differentiation, whereas an overproduction of these radicals causes aging or death of the cells.

Adenosine Diphosphate↗

[Menkes disease].

The Menkes or kinky hair disease is a rare, sex-linked systemic disorder of the copper metabolism. It is lethal in the first three years due to cerebral and cerebellar degeneration. Apropos of their case the authors summarise the knowledge on the diagnosis, pathogenesis and therapy.

Brain↗

[Progression of cutaneous T cell lymphoma in leukemia].

Transition of a (probably primary) cutaneous non-Hodgkin's lymphoma to T-stem cell leukaemia was observed in a case. Unusual clinical features, histological and laboratory data hampered the diagnosis-making of this rare disease. Using the ALL-BFM 90 HRG protocoll complete remission was achieved. Under the treatment varicella-zoster virus encephalitis took place.

Child↗

[Nephropathy in patients treated with ifosfamide].

Between 1987-1992 in the Department of Pediatric Oncology of Child Health Center at Miskolc the appearance of nephropathy caused by high dose Ifosfamide was studied (using different protocols) in patients with childhood malignancy. From 7 patients in 5 children nephrotoxicity were developed. In consequence of Ifosfamide rickets 2 patients are given continuous bicarbonate and calcitriol substitution. The authors call attention to the frequency of Ifosfamide nephropathy, low serum bicarbonate and phosphate concentration with glucosuria, aminoaciduria and hypochloremic acidosis were the manifestations of the disturbances of renal tubular functions. Prospective monitoring of these serum and urinary abnormalities may lead to early detection of tubulopathy and allow early replacement therapy.

Acidosis, Renal Tubular↗

Inhibition of the first component of the receptor current in Limulus photoreceptor.

The effect of l-cis-diltiazem on the light-activated current was investigated in Limulus ventral nerve photoreceptor. Intracellularly injected diltiazem blocked the first component, reduced the second one to about 50%, but hardly changed the third component of the receptor current. Extracellularly applied diltiazem elicited a similar effect, however, only after about 60 min incubation suggesting that the substance must diffuse into the cell; probably though the cut end of the axon, to be effective. Results suggest that the ion channels underlying the first component are similar to the cGMP-gated channels of rods and thus can be moderately permeable to calcium ions. This calcium influx is sufficient to regulate the gain of the second component which is activated by the inositol phosphate cycle.

Animals↗

Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: evidence for a role of protease in the early phase.

The antiviral activities of two substrate-based inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, UK-88,947 and Ro 31-8959, were studied in acute infections. H9 and HeLaCD4-LTR/beta-gal cells were infected either with HIV-1IIIB or a replication-defective virus, HIV-gpt(HXB-2). Both inhibitors were capable of blocking early steps of HIV-1 replication if added to cells prior to infection. Partial inhibition was also obtained by addition of inhibitor at the time of or as late as 15 min after infection. The inhibitors were ineffective if added 30 min postinfection. The inhibitory effects were studied by cDNA analysis with PCR followed by Southern blot hybridization and by infectivity assays allowing quantitation of HIV-1 in a single cycle of replication. When UK-88,947-treated H9 cells were coinfected with HIV-1 and human T-cell leukemia virus type I only the replication of HIV-1 was inhibited, demonstrating viral specificity. Pretreating the infectious virus stocks with the inhibitors also prevented replication, indicating that the inhibitors block the action of the viral protease and not a cellular protease. A panel of primer sets was used to analyze cDNA from cell lysates by PCR amplification at 4 and 18 h postinfection. Four hours after infection, viral specific cDNA was detected with all of the four primer pairs used: R/U5, nef/U3, 5' gag, and long terminal repeat (LTR)/gag. However, after 18 h, only the R/U5 and nef/U3 primer pairs and not the 5' gag or LTR/gag primer pair were able to allow amplification of cDNA. The results suggest a crucial role of HIV-1 protease in the early phase of viral replication. Although it is not clear what early steps are affected by the protease, it is likely that the target is the NC protein, as referred from our previous reports of the in situ cleavage of the nucleocapsid (NC) protein by the viral protease inside lentiviral capsids. The results suggest that it is not the inhibition of initiation and progression of reverse transcription but the stability of full-size unintegrated cDNA which is affected in the presence of protease inhibitors. Alternatively, the cleavage of the NC protein may be required for the proper formation of preintegration complex and/or for its transport to the nucleus.

Base Sequence↗