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Z Nagy

Publications and source records attributed to Z Nagy.

341 records · Page 19Linked to original sources
PubMedDate not supplied

Clustering of pathological features in Alzheimer's disease: clinical and neuroanatomical aspects.

We have analyzed the tendency of amyloid load, neuritic plaques and neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in clusters in 49 consecutive cases of Alzheimer's disease (AD). This clustering tendency of the pathology was analysed in relation to severity of clinical disease assessed within 6 months before death, duration and age at onset of disease and at death. Amyloid plaques showed only a slight tendency to cluster together while neuritic plaques and, even more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly strong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clustering tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic plaques showed similar but less pronounced and robust correlations between clustering and cognitive status. In the hippocampus NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that clustering characterises neuritic pathology but not diffuse amyloid deposits and significantly affects cognition. The discrepancies between the group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a significant effect on the cognitive status of AD patients.

Alzheimer Disease↗
PubMedDate not supplied

Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria.

We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.

Aged↗
PubMedDate not supplied

[Model studies on the transport processes of anticancer platinum complexes].

Potentiometric, calorimetric, NMR and stopped-flow kinetic studies were performed on the palladium(II) complexes of thioether and/or nitrogen donor ligands. The ternary systems always contained a tridentate ligand (dien, dipic, terpy and dianions of dipeptides, GlyGly, GlyAla and GlyMet) and a monodentate thioether (AcMet). The stability constants of thioether complexes were obtained by indirect potentiometric measurements using uridine as a competitive ligand. The thermodynamic parameters revealed that selectivity of palladium(II) for thioether binding can be significantly influenced by the other donor atoms around the metal ion. [Pd(terpy)]2+, [Pd(dipic)]2+ and [Pd(GlyMet)] had the lowest affinity for thioether binding and it was explained by steric and electronic effects. Ternary complexes of nitrogen donors have higher thermodynamic stability constants than that of the thioether complexes, but rate constants of the substitution reactions revealed that the formation of thioether complexes is the faster reaction. As a consequence, the thermodynamic equilibrium state of a multicomponent system is characterized by the coordination of N-donors, which are formed via the existence of thioether bonded intermediates.

Antineoplastic Agents↗
PubMedDate not supplied

The first histological demonstration of pancreatic oxidative stress in human acute pancreatitis.

Necrotizing acute pancreatitis is associated with an inflammatory explosion involving numerous pro-inflammatory mediator cascades and oxidative stress. Acinar oxygen free radical production aggravates pancreatic tissue damage, and promotes cellular adhesion molecule upregulation resulting in leukocyte adherence and activation. The cerium capture oxygen free radical histochemistry combined with reflectance confocal laser scanning microscopy allows the "in situ" histological demonstration of oxygen free radical formation in live tissues. Here we present a case report, where oxidative stress is demonstrated on a histological level for the first time in human acute pancreatitis. A 44-year-old male patient suffering from acute exacerbation of his chronic pancreatitis developed a pancreato-pleural fistula with amylase-rich left pleural exudate causing respiratory compromise. Subsequent to an urgent thoracic decompression a distal pancreatectomy and splenectomy was performed with the closure of abdomino-thoracic fistula. The postoperative course was uneventful, except for a transient pancreatico-cutaneous fistula, which healed after conservative treatment. To carry out cerium capture oxygen free radical histochemistry the resected pancreas specimen was readily perfused with cerium-chloride solution through the arteries on the resection surface. Frozen sections were cut, E-, P-selectin, ICAM and VCAM were labeled by immunofluorescence. The tumor-free margin of an identically treated pancreas carcinoma specimen served as a control. Intrapancreatic oxidative stress and cellular adhesion molecule expression were detected by confocal laser scanning microscopy. Numerous pancreatic acini and neighboring capillaries showed oxygen free radical-derived cerium-perhy-droxide depositions corresponding to strong local oxidative stress. Acinar cytoplasmic reflectance signals suggested xanthine-oxidase as a source of oxygen free radicals. These areas presented considerably increased endothelial P-selectin expression with adherent, oxygen free radical-producing polymorphonuclear leukocytes displaying pericellular cerium-reflectance. Modest ICAM upregulation was noted, E-selectin and VCAM expression was negligible. The control pancreas specimen showed minimal oxidative stress with weak, focal P-selectin expression. The development of deleterious pancreatic oxidative stress was based on indirect evidence in human acute pancreatitis. To the best of our knowledge this is the first report demonstrating persistent intrapancreatic oxidative stress histologically in human acute pancreatitis. We have noted P-selectin overexpression with a preponderance in the areas of acinar oxidative stress.

Adult↗
PubMedDate not supplied

Increased levels of amino terminal propeptide of type III procollagen are an unfavourable predictor of survival in systemic sclerosis.

OBJECTIVE: Investigation of the impact on survival of inflammatory parameters (C-reactive protein, ESR), markers of immune activation (serum soluble IL-2 receptor, soluble CD30), and N-terminal propeptide of type III procollagen levels (PIIINP) in systemic sclerosis (SSc). METHODS: In a prospective follow up study, clinical and laboratory data of 80 patients with SSc were evaluated. Kaplan-Meier survival curves and Cox proportional hazards model were used. Eighty cases with SSc were evaluated. Female/male ratio was 8/72. The mean (+/-SD) age was 49.3 (+/-12.3) years, 16 patients died during our mean follow up of 58.1 months. RESULTS: In the univariate analysis, the presence of a C-reactive protein level above 20 mg/l was an unfavourable prognostic sign (p<0.001). Increased level of PIIINP level also caused an unfavourable outcome of disease (p<0.001). Conversely, increased ESR, soluble IL-2 receptor, soluble CD30 levels, presence of anaemia, did not influence the prognosis. Male gender (p<0.005), diffuse cutaneous SSc, clinically significant lung involvement (p<0.001), kidney (p<0.0001), cardiac (p<0.05) manifestations including pericarditis (p<0.02) were unfavourable prognostic signs by univariate Kaplan-Meier method. Multivariate analysis by Cox proportional hazards model showed that the increased level of PIIINP (RR: 6.98), and presence of diffuse cutaneous SSc (RR: 5.14) were independent unfavourable prognostic signs. CONCLUSIONS: An increased collagen metabolism unfavourably influences the outcome of SSc. This parameter may also be a potential candidate as a disease activity marker.

Adult↗
PubMedDate not supplied

Survey of Raynaud's phenomenon and systemic sclerosis based on a representative study of 10,000 south-Transdanubian Hungarian inhabitants.

OBJECTIVES: To assess the prevalence of Raynaud's phenomenon (RP) and of RP associated systemic sclerosis (SSc) in a large regional representative study. METHODS: Ten thousand individuals aged between 14-65 years participated in face-to-face interviews. The stratified sample of the South-West Hungarian population was representative for age, sex and urban or rural residence. Individuals reporting complaints suggesting the presence of "clinically significant" RP were asked to undergo a clinical investigation. Patients showing complaints provoked by taking something out of the freezer (-20 degrees C) compartment of the refrigerator and/or whether they had experienced digital ulcers were sorted into this category. RESULTS: The overall prevalence of RP was at least 578.9/10,000, and the prevalence of "clinically significant" RP could be calculated as at least 87.7/10,000 inhabitants. In this latter group 17.2% of the cases had either established SSc or anticentromere antibody or scleroderma capillary pattern on nailfold capillaroscopy. SSc with "clinically significant" RP and/or ulcers was identified in a prevalence of 9.1/10.000 individuals, whilst there was a prevalence of 14.7/10,000 of RP with either anticentromere antibody or scleroderma capillary pattern. CONCLUSIONS: "Clinically significant" RP affects almost 1% of the population. We identified cases with early stages of scleroderma spectrum disorder showing either anticentromere autoantibody or scleroderma capillary pattern. The prevalence of SSc was found to be higher than expected. It is reasonable to screen "clinically significant" RP cases for scleroderma-related symptoms because this approach makes it possible to identify patients with both SSc and early scleroderma related symptoms.

Adolescent↗
PubMedDate not supplied

Effect of dimethylnitrosamine upon carbamoyl phosphate and ornithine utilization in rat liver.

Newborn CFY rats were intraperitoneally treated with a single dose of dimethylnitrosamine. Changes in the activity of carbamoyl-phosphate synthase I and II, ornithine carbamoyltransferase, aspartate carbamoyltransferase and dihydroorotase, i.e. utilization of ornithine and carbamoyl-phosphate pools were followed for 300 days. One or two months after treatment the activity of enzymes which utilize ornithine and carbamoyl-phosphate was enhanced in the cytosol, whereas the activity of the intramitochondrial enzymes in urea synthesis was decreased. Changes in the utilization of ornithine and carbamoyl-phosphate pools, characteristic of proliferating tissues, appeared to be irreversible.

Animals↗
PubMedDate not supplied

Isolated capillary proliferation in Leigh's syndrome.

An infant with hypotonia and recurrent apneic spells died with a diagnosis of pyruvate dehydrogenase deficiency and showed typical pathological changes of Leigh's syndrome at postmortem. Despite the prominence of symptoms suggesting dysfunction of brainstem respiratory centers during life, lesions were not found in the upper medulla. However, quantitative morphometric analysis demonstrated abnormal capillary hyperplasia in the region including and between the nucleus ambiguus and nucleus tractus solitarius. There was an average area of 8.0 +/- 2.5 x 10(6) mm2 occupied by capillaries per 0.75 mm2 field in the patient's brainstem, compared with 4.6 +/- 1.6 x 10(6) mm2 and 5.5 +/- 1.4 x 10(6) mm2 in two age-matched controls (p < 0.01). We speculate that capillary hyperplasia is a pathological marker of chronically impaired oxidative metabolism in the central nervous system in metabolic disease.

Brain↗
PubMedDate not supplied

Branched polypeptides as antigens for influenza virus hemagglutinin and T-cell receptor subunits.

The multiple antigenic peptide (MAP) method was applied to improve the immunogenicity of synthetic peptides representing distinct regions of the influenza virus hemagglutinin (HA). A tetrameric MAP with multiply incorporated overlapping B- and T-cell epitopes was combined with a particular HA sequence representing the slightly modified fusion peptide on the C-terminus of the Lys core (MAP-1). As a result of repeated injections of BALB/c mice with MAP-1 but not with the monomeric HA1C[Arg] peptide, the appearance of MAP-1-specific antibodies crossreactive with the acid-pretreated virus could be observed. In vitro studies revealed the potency of the MAP-1 structure to induce proliferation of HA1C[Arg]-primed T-cells, and in vivo studies demonstrated the protective feature of the immune response elicited by MAP-1 and to a lesser extent by the monomeric HA1C[Arg]. The increased level of MAP-1 specific antibodies upon viral challenge shows the activation of MAP-1-specific B- and/or T-cells. The advantage of the previously verified FP3 helper T-cell epitope included in MAP-1 was further utilized to synthesize chimeric structures comprising short fragments of the zeta of (MAP-2) or delta (MAP-3) subunits of the T-cell antigen receptor (TCR) complex. The selected peptides of the zeta and delta-chain regions failed to elicit an antibody response in BALB/c mice as tetra- or octamers, but the inclusion of the modified fusion region resulted in an immunogenic construction.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

A survey of four years of experience with intracytoplasmic sperm injection.

The present report covers the results of a 38-month period in which 2853 consecutive intracytoplasmic sperm injection (ICSI) cycles were performed in 1953 couples. These couples were afflicted with male factor infertility and had at least one previous failed conventional in vitro fertilization (IVF) treatment cycle. In other couples, the husband had semen parameters incompatible with conventional IVF or suffered from excretory or secretory azoospermia where it was possible to recover spermatozoa by microsurgical epididymal sperm aspiration (mesa) or by testicular sperm extraction (tese) procedure. Overall, the 2-PN fertilization rate was 62% per retrieved metaphase II oocyte and 70% per successfully injected metaphase II oocyte. Embryo transfer was performed in 91% of started cycles. The cumulative pregnancy rate (positive HCG) was 34% per started ICSI treatment and 37% per embryo transfer.

Adult↗
PubMedDate not supplied

[Sandostatin treatment in postoperative external digestive fistulae].

The aim of the conservative treatment of postoperative external digestive fistulae is to obtain a reduction of the output, thus favoring spontaneous closure and shortening outcome. A retrospective comparative study has been performed on two groups of patients with postoperative anastomotic gastrointestinal and pancreatic fistulae. Group A included 18 cases (14 anastomotic, 4 pancreatic fistulae) receiving conventional treatment only. Group B included 25 cases (18 anastomotic and 7 pancreatic fistulae) in which Sandostatin was associated to conventional therapy, using daily doses ranging from 0.1 mg to 0.3 mg, administered after variable intervals after fistulas' occurrence. Duration of treatment ranged from 1 to 25 days. In group A, 27.77% of the cases were cured in comparison with group B in which the healing rate increased to 56%. Global hospital mortality rate was 25.58% (11 cases). In group A this was 44.44% (8 cases) in comparison with group B with 12% (3 cases) only. As a conclusion of our study, the use of Sandostatin is remarkable effective in the treatment of external digestive postoperative fistulae. Thus a doubling of healing rate and a reduction by 73% of mortality rate was achieved.

Cutaneous Fistula↗
PubMedDate not supplied

Nitric oxide production and MDR expression by human brain endothelial cells.

The endothelium both initiates and responds to a cascade of events triggered by cytokines. Enhanced formation of NO, especially by inducible nitric oxide- synthase (i NOS), is largely stimulated by tumor necrosis factor (TNF). Nitrogen oxides are reactive intermediate molecules functioning in neural transmission, and vasodilatation. The aim of our study was to investigate the effect of TNF and Staphylococcus aureus, a TNF inducing agent on the NO production of brain endothelial cells in vitro. The effect of the same agent was investigated on the MDR expression of endothelial cells. Both TNF and Staphylococcus aureus resulted in enhanced NO production. Western blot analysis showed enhanced expression of iNOS, which could be inhibited by pentoxifylline, an inhibitor of TNF synthesis. Flow cytometric analysis revealed that the brain capillary endothelial cells exerted P-glycoprotein expression, which was not influenced by TNF. However, the mdr function itself in these cells was decreased by TNF. Cultured endothelial cells are excellent tools for the investigation of the possible connection between the NO production and MDR function, and for the estimation the effect of different agents influencing these activities, which might be important in blood-brain barrier function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗