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Biomedical subjects

Z Nagy

Publications and source records attributed to Z Nagy.

At least 109 records · Page 6Linked to original sources
PubMed1998

Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis in rats.

UNLABELLED: The purposes of this study were to determine the tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on cytokine production. METHODS: acute pancreatitis was induced by the retrograde injection of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats. The serum amylase activity, the wet pancreatic weight/body weight ratio, and the TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed 6, 24, 48 or 72 h after the operation. RESULTS: the TNF bioassay revealed high levels of TNF (30.2 +/- 5.4 U/ml, 35.0 +/- 5.0 U/ml and 36.6 +/- 6.0 U/ml) in the control group at 6, 24 and 48 h and (54.1 +/- 20 U/ml and 10.9 +/- 4.2 U/ml) in the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased levels in the pentoxifylline-treated group at 48 h (7083 +/- 2844 pg/ml, 6463 +/- 1307 pg/ml, 10,329 +/- 5571 pg/ml vs 137.5 +/- 85.5 pg/ml, respectively, P < 0.05). The high mortality observed in the pancreatitis group (43%) was decreased by pentoxifylline administration to 11%. CONCLUSION: these results demonstrate that pentoxifylline very effectively inhibits cytokine production in acute pancreatitis.

Acute Disease↗
PubMed1998

A hemagglutinin-based multipeptide construct elicits enhanced protective immune response in mice against influenza A virus infection.

Multipeptide constructs, comprising adjacent sequences of the 317-341 intersubunit region of immature influenza A hemagglutinin (H1N1), were designed and the functional properties of these branched peptides were compared to that of the corresponding linear peptides. In vivo studies revealed that the immunogenicity of the peptides was dependent on the presence of the hydrophobic fusion peptide (comprised in FP3), encompassing the N-terminal 1-13 sequence of the HA2 subunit. Antibody and T cell recognition, however, was directed against the 317-329 HA1 sequence, comprised in the P4 peptide. Multiple copies of P4, covalently linked by branched lysine residues, significantly enhanced the efficiency of antibody binding and the capacity of peptides to elicit B- and T-cell responses. A fraction of peptide induced antibodies reacted with immature or with proteolitically cleaved hemagglutinin (HA) molecules pretreated at low pH. Immunization with a multipeptide construct, (P4)4-FP3, not only resulted in elevated antibody and T cell responses but conferred enhanced protection against lethal A/PR/8/34 (H1N1) infection as compared to its subunit peptides. The beneficial functional properties of this artificial peptide antigen may be acquired by multiple properties including: (i) stabilized peptide conformation which promotes strong, polyvalent binding to both antibodies and MHC class II molecules; (ii) appropriate P4 conformation for antibody recognition stabilized by the covalently coupled fusion peptide, resulting in the production of virus cross reactive antibodies which inhibit the fusion activity of the virus; (iii) activation of peptide specific B cells which potentiate antigen presentation and peptide specific T cell responses; and (iv) generation of helper T cells which secrete lymphokines active in the resolution of infection.

Animals↗
PubMed1998

Natural killer cell mediated cytotoxicity against VERO target cells; the suppressive effect of pentoxifylline.

The K-562 cell line is widely known and used as a NK cell target. In this study we report that VERO (African green monkey kidney epithelial cell line) is an excellent target of the human NK cell cytotoxicity. Considerable cytotoxicity was observed in a 4 h 51Cr release assay with nonadherent and immunomagnetically separated CD56+ NK cells from PBMC. On the contrary, adding K-562 cells as cold target to the assay the cytotoxicity significantly decreased. Using a standard chromium-release assay the NK cell activity (NKCA) against VERO cells was investigated in a population of healthy volunteers (mean value of cytotoxicity was 26.6%) and compared with the values of cytotoxicity against K-562 target cells (32.6%). The difference was not significant (P > 0.05). The suppressive effect of PTX on in vitro NK cell activity was observed at concentration of 100 microg/ml using VERO target cells as well as K-562 cells. Our studies provide the first evidence that the NK cell activity is suppressed in vitro by PTX using VERO cells as NK target cells.

Adult↗
PubMed1998

Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4.

The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development of lesions secondary to ischaemia and reperfusion. The endothelial cell monolayer of the brain microvasculature is the critical interface between the blood-borne mediators and brain tissue. The involvement of these cells in complement production and regulation has not been well documented. In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells obtained from human brain microvessels has been characterized. Interferon gamma upregulates the production of all the complement factors studied. Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue.

Brain↗
PubMed1998

The cell division cycle and the pathophysiology of Alzheimer's disease.

Evidence is growing of a role of apoptosis in neurodegenerative disorders including Alzheimer's disease. Recent research indicates that cell cycle disturbances may promote apoptosis in neurodegenerative diseases. In this commentary we will discuss the control of the cell cycle in mammalian cells in general and in the central nervous system in particular. We then summarize the evidence for cell cycle perturbations in Alzheimer's disease and discuss the possible significance these may have for the development of pathological changes in this disease. Our working hypothesis is that, contrary to previous belief, neurons in the adult human brain are capable of re-entering the cell division cycle. The progression of the cell cycle is normally arrested at an early stage and neurons are able to re-differentiate. However, in Alzheimer's disease the cell cycle is allowed to progress into the G2 phase. At this stage re-differentiation is not possible and the neurons will suffer one of two fates: either they will die via an apoptotic pathway or they may produce Alzheimer-type pathology.

Adult↗
PubMed1998

Fine needle aspiration versus open biopsy for testicular sperm recovery: a controlled study in azoospermic patients with normal spermatogenesis.

This retrospective controlled study aimed at comparing two techniques for recovering testicular spermatozoa in azoospermic patients undergoing intracytoplasmic sperm injection (ICSI). 102 men suffering from infertility because of obstructive azoospermia had ICSI using testicular spermatozoa recovered either by open excisional biopsy (n = 51), or by fine needle aspiration (FNA) (n = 51). A higher average number of spermatozoa were recovered after open biopsy than after FNA, but no significant differences in either fertilization rates or cleavage rates were observed after ICSI with spermatozoa retrieved by the two techniques. Neither was there any significant difference in ongoing pregnancy and implantation rates: in the FNA group, these figures were respectively 19.6% per cycle and 7.8% per embryo transferred and in the open biopsy group 21.6 and 7.1%. We conclude that ICSI with testicular spermatozoa recovered by FNA yields results comparable to those obtained with spermatozoa recovered by open biopsy in azoospermic patients with normal spermatogenesis. However a prospective study is needed to confirm the present results and to assess recovery rates and patient comfort for the two methods.

Biopsy↗
PubMed1998

Intracytoplasmic sperm injection: laboratory set-up and injection procedure.

Intracytoplasmic sperm injection (ICSI) as treatment for male-factor infertility has been introduced worldwide in the past few years in many laboratories using assisted reproduction techniques. Some changes in the existing set-up are necessary before implementing this procedure. The equipment can be divided into two groups: that required for preparation of the microtools and that required for the microinjection procedure itself. A pipette puller, grinder and microforge are necessary for preparation of the microtools. The correct settings and use of these instruments are of crucial importance in preparing a good needle, which in turn is crucial to the injection procedure itself. The microscope has to be equipped with a heated stage, correct optics and manipulators and injectors. The correct settings and use of this equipment also influence the injection procedure and may influence the success rate. Retrospective analysis of the evolution of ICSI in our centre clearly shows a marked improvement following the introduction of some modifications into the procedure. These modifications were (i) reducing the concentration of hyaluronidase used for cumulus and corona radiata removal, (ii) selecting a motile spermatozoon that was immobilized prior to the injection and (iii) aspiration of cytoplasm to ensure rupture of the oocyte membrane. The injection procedure itself can also be influenced by oocyte characteristics. It has been reported that the reaction of the oocyte to the penetration by the pipette has an influence on the success rate. The ICSI procedure has about the same success rate as IVF in cases of non-male infertility. However, work can still be done to improve the success rate of this procedure.

Fertilization in Vitro↗
PubMed1998

Perturbation of the integrity of the blood-brain barrier by fibrinolytic enzymes.

The action of fibrinolytic enzymes (plasmin, miniplasmin, neutrophil leukocyte elastase) on the blood-brain barrier is investigated. The binding and the effects of the fibrinolytic enzymes are studied in the first subcultivation of human brain capillary endothelial cells. 125I-labeled plasmin, miniplasmin and neutrophil leukocyte elastase bind to confluent monolayers of cultured endothelial cells with dissociation constants of 1 x 10(-8) mol/l, 4.8 x 10(-7) mol/l and 1.8 x 10(-8) mol/l, respectively, and the number of binding sites varies between 2.3 x 10(5) and 7.5 x 10(6) per cell. Following treatment of the cultured cells with purified and active-site titrated proteases, the changes in morphology of individual cells are analyzed with computerized morphometry. At low concentrations (in nanomolar range) all studied fibrinolytic proteases induce reduction of the cell area; the minimal size is achieved in 20-80 min after the application of an enzyme and the effect is completely reversed in 15 min after its removal. A possible in-vivo consequence of these in-vitro findings is studied in an organ-perfusion model: rat hemisphere is perfused with a protease solution followed by a circulating phase-borne tracer (horse-radish peroxidase). In perfused rat hemisphere, the fibrinolytic enzymes open the blood-brain barrier to the circulation-borne tracer. These results support the concept that fibrinolytic enzymes interact with the brain microvascular endothelium and thus affect the integrity of the blood-brain barrier through active cell contraction.

Blood-Brain Barrier↗
PubMed1998

Regulation of endothelin release from human brain microvessel endothelial cells.

After approval by the Local Ethical Committee, brain microvessel endothelial cells from human cadavers were isolated by enzymatic digestion and gradient centrifugation. Basal levels of endothelin-1 (ET) in the supernatant increased over time (3 h, 18.3 +/- 4.3 pg/ml; 6 h, 31.3 +/- 1.1 pg/ml; 24 h, 88.0 +/- 5.7 pg/ml; 48 h, 86.3 +/- 11.2 pg/ml, mean +/- SD). Tumor necrosis factor-alpha (TNF-alpha) (270 U/ml) increased ET concentration dose-dependently: 3 h, 190 +/- 70%; 24 h, 217 +/- 39%; 48 h, 207 +/- 5%; TNF-alpha at 210 U/ml: 3 h, 137%; 24 h, 170%; 48 h, 212% (values are relative changes from control, run in parallel to the stimulated wells). Interleukin-1 alpha (IL-1 alpha) (38.8 U/ml) also increased ET dose-dependently: (3 h, 129%; 24 h, 161%; 48 h, 212%; IL-1 alpha 1.4 U/ml: 3 h, 116%; 24 h, 122%; 48 h, 180%). Lipoprotein (a) (Lp(a)) had a dual effect on ET, increasing ET in the first 3 h but reducing it by the end of the 48-h observation period. This effect was not dose-dependent in the concentration range tested: Lp(a) 450 micrograms/ml; 3 h, 188%; 24 h, 91%; 48 h, 85%; Lp(a) 360 micrograms/ml: 3 h, 180%; 24 h, 94%; 48 h, 52%). Lp(a) reduced the stimulatory effect of cytokines on ET release. Maximal values at 48 h were TNF-alpha 207%, TNF-alpha + Lp(a) 91%, IL-1 alpha 212%, IL-1 alpha + Lp(a) 64%. In HPLC analysis, the total ET-like immunoreactivity co-eluted with the synthetic human ET standard. A cell culture of human brain microvessel endothelial cells was established. TNF-alpha and IL-1 alpha increased ET secretion, whereas Lp(a) had a dual effect. When given together, Lp(a) reduced the effect of cytokines on ETs.

Brain Chemistry↗
PubMed1997

[Polymorphism of the 52 triplet gene (nucleotide 253) of the TSH receptor in Basedow-Graves patients and in healthy controls].

It has been analysed the polymorphism of the first exon of TSH receptor gene, at the first nucleotide of the triplet 52 of the genomic DNA (CCC/ACC, Pro/Thr) in Graves' disease and control population and was not found connection between the genetic background, clinical picture and some immunological parameters. Genomic DNA was obtained from formalin-fixed, paraffin embedded thyroid tissue of patients with Graves' disease underwent subtotal thyroidectomy and from peripheral blood leukocytes. The first exon and small part of the first intron of the TSH-R gene was amplified by PCR. The motif was amplified by the primers and primers includes restriction site of the Tth 111 I restriction enzyme and mutant form of the examined nucleotide. Genomic DNA having only wild allele was detected at 189 bp, while mutant allele was digested a 167 and a 22 bp fragments. Three persons (two female and one male) of the 32 patients with Graves' disease had mutation A253 in heterozygotic form: The patient with mutation A253 had no any symptoms of Graves' ophthalmopathy. No correlation was found between mutation A253 and the levels of anti-TSH-R-, anti TG, anti-TPO and anti-eye muscle antibodies. Surprisingly, it was found mutation of heterozygous genotype in two control individuals (one female and one male) of 14 without any symptoms of thyroid disease and negative laboratory findings. Finally, it has not been found the association of the 253 nucleotide of the codon 52 polymorphism with Graves' disease and ophthalmopathy and the allele A253 has no pathogenetic relevance in Graves' disease. On the other hand, it cannot be excluded that other mutation or sequence polymorphism in the remainder of TSH-R extracellular domain might be important in autoimmune mechanism of Graves' disease.

Adolescent↗
PubMed1997

[Cytokines in experimental acute pancreatitis].

The authors induced acute necrotizing pancreatitis in Wistar rat by intraductal injection of taurocholic acid (150 microliters or 200 microliters 6%). Plasma values of amylase, TNF, IL-6 levels and wet pancreas weight/body weight ratio have been determined. Histologic analysis of pancreas proved severe acute necrotizing pancreatitis with microabscess formation and beginning respiratory distress syndrome was observed in the lungs, TNF and IL-6 levels increased significantly after administration of 200 microliters 6% taurocholic acid. The authors emphasise the importance of cytokines in the development of acute necrotizing pancreatitis.

Amylases↗
PubMed1997

Predictors of survival in 171 patients with systemic sclerosis (scleroderma).

Predictors of survival were determined in 171 patients with systemic sclerosis by univariate analysis, and the Cox proportional hazards model using both cross sectional data at entry into the follow-up and time-dependent follow-up data. Clinical and laboratory data were evaluated from 1982 to the end of 1993. The presence of diffuse scleroderma, kidney and cardiac involvements were unfavourable prognostic signs in both the univariate analysis, and the Cox proportional hazards models. The Cox model, using the variables detected at study entry, indicated that pericarditis, and anaemia were bad prognostic signs. Analysis with time dependent data has not been reported in systemic sclerosis. The appearance of pigmentation disturbances, anaemia, and respiratory failure during the follow-up also caused a poor prognosis of the disease by the Cox model. In the stepwise selection models, diffuse scleroderma, internal organ manifestations including renal, and cardiac involvements were predominantly selected as the most unfavourable factors for survival. As to the extent of skin involvement and internal organ manifestations, the general behaviour of the disease seems to be similar throughout the world. The early appearance of pericarditis and pigmentation disturbances at study entry are bad prognostic signs.

Adult↗
PubMed1997

Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions.

Recent studies, showing that cell cycle-related nuclear proteins p105 and Ki-67 are associated with Alzheimer's disease (AD)-related cytoskeletal pathology, suggested that these proteins, in addition to their functions in regulating the cell cycle, may have more specialised functions in the adult nervous system. In order to test this hypothesis we studied the expression of the cell cycle-related proteins Ki-67, pCNA and p53 in the hippocampi of 33 subjects, including some with AD or other neurodegenerative disorders and some with no neurological disease. By immunohistochemistry we found nuclear expression of Ki-67 in all subregions of the hippocampus, with the highest levels in the dentate gyrus. Both neurons and glial cells expressed this protein. The proportion of cells positive for Ki-67 and the distribution pattern varied considerably depending on the pathological diagnosis. Neuronal nuclear expression of Ki-67 was increased in AD but was also elevated in young Down's syndrome subjects and in those with Pick's disease. Expression of this protein was therefore not AD-specific. We did not find nuclear pCNA or p53 expressed in our patient groups. Contrary to previous studies AD-type neurofibrillary tangles were not labelled with any of the cell cycle markers used. The presence of nuclear Ki-67 expression indicates that some hippocampal neurons are not in the quiescent G0 phase but have re-entered the cell cycle. The absence of nuclear pCNA or p53 suggests that the cycle is arrested in G1. The significance of our findings and their relationship to the production of neurodegenerative cell death via an apoptotic mechanism are discussed.

Adolescent↗
PubMed1997

Cell cycle markers in the hippocampus in Alzheimer's disease.

Using immunohistochemistry we have analysed the nuclear expression of cyclins A, B, D, and E in neurones in the hippocampi of control subjects and patients suffering from various neurodegenerative disorders including. Alzheimer's disease (AD). Cyclins A and D could not be detected but varying degrees of cyclin E expression were found in all patient groups including control subjects. Cyclin B expression was not detected in control subjects but it was expressed in the subiculum, dentate gyrus and CA1 region in patients with AD-type pathology and in the CA2 region and the dentate gyrus of cases of Pick's disease. These results suggest that some neurones may have re-entered the cell cycle. The expression of cyclin E without cyclin A expression may indicate an arrest in G1 with the possibility of re-differentiation and exit from G1 to G0. The expression pattern of cyclin E indicates that re-entry into the cell cycle is possible even in control patients, but it is accentuated in patients with AD-related pathology. However, cyclin B was only expressed in AD patients and occurred in areas that were severely affected by pathology. Neurones with cyclin B-reactive nuclei in AD were AT8 positive but did not contain fully developed tangles. In neurones, where cyclin B is expressed, it would appear that the G1/S checkpoint has been bypassed and that the cell cycle is arrested in G2. It is proposed that these neurones do not have the opportunity for subsequent re-differentiation. Since factors known to be present in G2 seem to be responsible for microtubule destabilisation and hyperphosphorylation of tau we hypothesise that cell cycle disturbances may be important in the pathogenesis of AD.

Adolescent↗
PubMed1997

Effect of desferrioxamine cardioplegia on ischemia-reperfusion injury in isolated rat heart.

BACKGROUND: The protective effect of desferrioxamine against myocardial ischemia-reperfusion injury remains uncertain. In this study we examined a broad range of ischemia-reperfusion indices to determine the effect of desferrioxamine cardioplegia in a model that reflects surgical practice. METHODS: Isolated rat hearts were subjected to 90 minutes of ischemia with cold cardioplegia, with or without 0.5-mmol/L desferrioxamine. Left ventricular mechanical function and the levels of thiobarbituric acid-reactive substances and nonprotein thiol compounds were measured after reperfusion. Electron microscopic analysis of mitochondria was performed using diaminobenzidine staining, together with histochemical staining for glycogen and marker enzymes in left ventricular muscle and the atrioventricular node. RESULTS: The desferrioxamine group showed better preservation of diastolic function (chamber stiffness coefficient at 15 minutes and maximum rate of decrease of left ventricular pressure at 45 minutes of reperfusion). Histochemical analysis showed that mitochondria-specific succinate dehydrogenase and the nonspecific esterase of the atrioventricular node were better preserved in the desferrioxamine group. CONCLUSIONS: The findings from this study indicate that there is added protection against ischemia-reperfusion injury when desferrioxamine is added to the cardioplegic solution; however, the study also highlighted that, in this clinically applicable model, desferrioxamine is not universally protective against all aspects of ischemia-reperfusion injury.

Animals↗
PubMed1997

Quality of frozen-thawed testicular sperm and its preclinical use for intracytoplasmic sperm injection into in vitro-matured germinal-vesicle stage oocytes.

OBJECTIVE: To study the effects of cryopreservation on the quality of human testicular spermatozoa and the efficiency of intracytoplasmic sperm injection (ICSI) with frozen-thawed testicular sperm into metaphase II oocytes in vitro-matured from the germinal-vesicle stage oocyte. DESIGN: Preclinical freezing study on supernumarary testicular spermatozoa after ICSI. SETTING: Tertiary IVF center coupled with an institutional research environment. PATIENT(S): Twenty-nine patients undergoing excisional testicular biopsy for ICSI. INTERVENTION(S): Isolated testicular spermatozoa were cryopreserved and thawed; frozen-thawed motile testicular spermatozoa were microinjected. MAIN OUTCOME MEASURE(S): Prefreezing and post-thawing motility and viability, survival rate, fertilization rate, cleavage rate, and embryo quality after ICSI. RESULT(S): Mean percentage motility decreased from 21% before freezing to 6% after thawing. Vitality was impaired to a similar extent, decreasing from 68% to 22% (32% recovery rate). Injection of frozen-thawed testicular spermatozoa into in vitro-matured oocytes resulted in a fertilization rate of 50.9%. Cleavage rate was severely impaired. Half of the fertilized oocytes became arrested in the one-cell stage. CONCLUSION(S): Despite the low quality of the fresh testicular spermatozoa, a high percentage of prepared testicular sperm fractions showed survival and motility after the freezing and thawing process. Injection of frozen-thawed testicular sperm into matured oocytes resulted in fertilization rates comparable with these with fresh testicular sperm, but cleavage rates were severely impaired, which might be due to source of oocytes used for ICSI.

Adult↗