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Biomedical subjects

L Nagy

Publications and source records attributed to L Nagy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Analytical performance characteristics of thin and thick film amperometric microcells.

The analytical performance of amperometric microcells with different electrode geometries is compared for enzyme activity measurements. The microcells were fabricated with thin film photolithography or thick film screen-printing in four different designs. The cells made with the thin film process used flexible substrate with microelectrode array or a circular, disk-shaped working electrode. The screen-printed working electrodes had semicircle or disk shape on ceramic chips. Putrescine oxidase (PUO) activity measurement was used as a model. The determination of PUO activity is important in the clinical diagnosis of premature rupture of the amniotic membrane. An electropolymerized m-phenylenediamine size-exclusion layer was used to eliminate common interferences. The size exclusion layer revealed also to be advantageous in protecting the electrodes from fouling by putrescine (enzyme substrate). The electrode fouling of bare electrodes was insignificant for screen-printed electrodes, but very severe for electroplated platinum working electrodes. The microelectrode array electrodes demonstrated smaller RSD and higher normalized sensitivities for hydrogen peroxide and PUO activity. All the other electrodes were demonstrating comparable analytical performances.

Electrochemistry↗
PubMed2001

Avoidance of vascular compression in decompressive surgery for brain edema caused by trauma and tumor ablation.

BACKGROUND: In case of severe brain swelling especially caused by trauma or other operative manipulation (tumor ablation), decompressive craniectomy with durotomy has not resulted in significant chances of recovery. Decompressive craniectomy has been defined only as an option within guidelines. METHOD: A new operative technique was developed to improve the efficacy of decompressive surgery. With an increase in intracranial pressure (ICP) threatening with brainstem herniation, wide bilateral craniectomy was carried out, followed by dura opening and subsequent formation of a vascular tunnel in a simple way--using hemostatic sponge cushions--around the main cortical veins at the entering points of the herniated area. The maintenance of vessel patency prevents the herniated brain segment from venous congestion, i.e., from further swelling and necrosis. RESULTS: Twenty operations with traumatic brain edema were performed using this vascular tunnel method. All patients were exposed to surgery in the state of coma. One operation was performed after tumor removal. The results were promising in comparison with the well-known surgical or conservative treatment. DISCUSSION: Applying very strict selection criteria (Glasgow coma scale < 6, signs of severe edema on CT, or intracranial pressure permanently > or = 30 mmHg) in this small series of patients with severe brain injury, good results were achieved using the new operative technique. In case of postoperative edema after tumor ablation, it also showed promising results.

Adult↗
PubMed2001

A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.

ATP Binding Cassette Transporter 1↗
PubMed2001

Photoinhibition of carotenoidless reaction centers from Rhodobacter sphaeroides by visible light. Effects on protein structure and electron transport.

Inhibition of electron transport and damage to the protein subunits by visible light has been studied in isolated reaction centers of the non-sulfur purple bacterium Rhodobacter sphaeroides. Illumination by 1100 muEm(-2) s(-1) light induced only a slight effect in wild type, carotenoid containing 2.4.1. reaction centers. In contrast, illumination of reaction centers isolated from the carotenoidless R26 strain resulted in the inhibition of charge separation as detected by the loss of the initial amplitude of absorbance change at 430 nm arising from the P(+)Q(B) (-) --> PQ(B) recombination. In addition to this effect, the L, M and H protein subunits of the R26 reaction center were damaged as shown by their loss on Coomassie stained gels, which was however not accompanied by specific degradation products. Both the loss of photochemical activity and of protein subunits were suppressed in the absence of oxygen. By applying EPR spin trapping with 2,2,6,6-tetramethylpiperidine we could detect light-induced generation of singlet oxygen in the R26, but not in the 2.4.1. reaction centers. Moreover, artificial generation of singlet oxygen, also led to the loss of the L, M and H subunits. Our results provide evidence for the common hypothesis that strong illumination by visible light damages the carotenoidless reaction center via formation of singlet oxygen. This mechanism most likely proceeds through the interaction of the triplet state of reaction center chlorophyll with the ground state triplet oxygen in a similar way as occurs in Photosystem II.

Journal Article↗
PubMed2001

PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is highly expressed in lipid-accumulating macrophages of the coronary artery. In light of this, the wide-spread clinical use of thiazolidinediones (TZDs) in the treatment of type II diabetes raises concerns about the role of PPAR-gamma in macrophage function and disease progression. To define the role of PPAR-gamma in macrophage biology, we used homologous recombination to create embryonic stem cells that were homozygous for a null mutation in the PPAR-gamma gene. We demonstrate here that PPAR-gamma is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo. In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages. Both 15-deoxy-Delta12,14prostaglandin J2 and thiazolidinediones have anti-inflammatory effects that are independent of PPAR-gamma. We show that PPAR-gamma is required for positive effects of its ligands in modulating macrophage lipid metabolism, but that inhibitory effects on cytokine production and inflammation may be receptor independent.

3T3 Cells↗
PubMed2001

Rigid internal fixation of basilar fractures of the proximal phalanges by cancellous bone grafting only.

Ten patients with 13 basilar metaphyseal impaction fractures of the proximal phalanges of the fingers were treated with "rigid internal fixation" by bone grafting alone. When retrospectively reviewed at a mean follow-up of 32 months, bone healing had occurred without any relevant secondary displacement of the fracture fragments. The final ranges of motion were good and return to work was quicker than expected.

Adolescent↗
PubMed2001

Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents.

Both retinoid X receptor (RXR)-selective agonists (rexinoids) and thiazolidinediones (TZDs), PPAR (peroxisome proliferator-activated receptor)-gamma-specific ligands, produce insulin sensitization in diabetic rodents. In vitro studies have demonstrated that TZDs mediate their effects via the RXR/PPAR-gamma complex. To determine whether rexinoids lower hyperglycemia by activating the RXR/PPAR-gamma heterodimer in vivo, we compared the effects of a rexinoid (LG100268) and a TZD (rosiglitazone) on gene expression in white adipose tissue, skeletal muscle, and liver of Zucker diabetic fatty rats (ZDFs). In adipose tissue, rosiglitazone decreased tumor necrosis factor-alpha (TNF-alpha) mRNA and induced glucose transporter 4 (GLUT4), muscle carnitine palmitoyl-transferase (MCPT), stearoyl CoA desaturase (SCD1), and fatty acid translocase (CD36). In contrast, LG100268 increased TNF-alpha and had no effect or suppressed the expression of GLUT4, MCPT, SCD1, and CD36. In liver, the rexinoid increased MCPT, SCD1, and CD36 mRNAs, whereas rosiglitazone induced only a small increase in CD36. In skeletal muscle, rosiglitazone and LG100268 have similar effects; both increased SCD1 and CD36 mRNAs. The differences in the pattern of genes induced by the rexinoids and the TZDs in diabetic animals found in these studies suggests that these compounds may have independent and tissue-specific effects on metabolic control in vivo.

Adipose Tissue↗
PubMed2001

Thermal and structural changes of photosynthetic reaction centers characterized by photoacoustic detection with a broad frequency band hydrophone.

Photoacoustic measurements using a broad frequency band hydrophone were carried out in photosynthetic reaction centers (RC) isolated from Rhodobacter sphaeroides R-26 purple bacteria. Data were extracted on enthalpy and volume changes accompanying the primary steps after excitation in the range of 0-500 microseconds aimed at further characterizing the thermodynamic properties of the RC. Quinone titration showed that the volume contraction accompanying the electron transport is sensitive to the molecular species occupying the secondary quinone site. delta VM = 14.4, 7.7 and 4.3 cm3 molar volume contractions were calculated from the measured parameters for 1, 2 and 0.07 quinone/RC after light excitation. Comparing the enthalpy changes (delta H) to the Gibbs free energy data in the literature, a rather large (26%) entropic contribution to the free energy changes (delta G) is estimated for the P*QAQB-->P+QA-QB electron transport (where QA and QB represent primary and secondary quinones, respectively). This is in contrast to previous estimations that delta G = delta H in these processes. On the other hand, only a small (4%) entropic contribution to the delta G of the P*QAQB-->P+QAQB- process is estimated, in agreement with the literature data. Our results are in good agreement with the data obtained earlier (Edens et al. [2000] J. Am. Chem. Soc. 122, 1479-1485).

Electron Transport↗
PubMed2000

Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells.

The attraction, binding, and entry of monocytes into the vessel wall play an important role in atherogenesis. We have previously shown that minimally oxidized/modified LDL (MM-LDL), a pathogenically relevant lipoprotein, can activate human aortic endothelial cells (HAECs) to produce monocyte chemotactic activators. In the present study, we demonstrate that MM-LDL and oxidation products of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) activate endothelial cells to synthesize monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8). Several lines of evidence suggest that this activation is mediated by the lipid-dependent transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha), the most abundant member of the PPAR family in HAECs. Treatment of transfected CV-1 cells demonstrated activation of the PPARalpha ligand-binding domain by MM-LDL, Ox-PAPC, or its component phospholipids, 1-palmitoyl-2-oxovalaroyl-sn-glycero-phosphocholine and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine; these lipids also activated a consensus peroxisome proliferator-activated receptor response element (PPRE) in transfected HAECs. Furthermore, activation of PPARalpha with synthetic ligand Wy14,643 stimulates the synthesis of IL-8 and MCP-1 by HAECs. By contrast, troglitazone, a PPARgamma agonist, decreased the levels of IL-8 and MCP-1. Finally, we demonstrate that unlike wild-type endothelial cells, endothelial cells derived from PPARalpha null mice do not produce MCP-1/JE in response to Ox-PAPC and MM-LDL. Together, these data demonstrate a proinflammatory role for PPARalpha in mediation of the activation of endothelial cells to produce monocyte chemotactic activity in response to oxidized phospholipids and lipoproteins.

Animals↗
PubMed2000

Personality traits among currently eating disordered, recovered and never ill first-degree female relatives of bulimic and control women.

BACKGROUND: A combined family study and recovered study design was utilized to examine several hypothesized relationships between personality and bulimia nervosa (BN). METHODS: We studied 47 women with a lifetime history of DSM-III-R BN (31 currently ill and 16 recovered), 44 matched control women (CW) with no history of an eating disorder (ED), and their first-degree female relatives (N = 89 and N = 100, respectively), some of whom had current or previous EDs. RESULTS: BN probands' relatives with no ED history had significantly elevated levels of perfectionism, ineffectiveness, and interpersonal distrust compared to CW probands' relatives with no ED history. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions were found among the previously eating disordered relatives of bulimic probands compared to their never ill relatives. Finally, a sense of alienation and emotional responsivity to the environment were elevated among currently ill compared to recovered bulimic probands. CONCLUSIONS: The fact that perfectionism, ineffectiveness and interpersonal distrust are transmitted independently of an ED in relatives suggests that they may be of potential aetiological relevance for BN. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions are more likely consequent to, or exacerbated by, previously having experienced the illness. Finally, a sense of alienation and emotional responsivity to the environment are more likely to be associated with currently having BN.

Adolescent↗
PubMed2000

Apoptosis-linked in vivo regulation of the tissue transglutaminase gene promoter.

Tissue transglutaminase (tTG) is upregulated in various cells undergoing apoptosis. To investigate the transcriptional regulation of tTG a mouse strain carrying a beta-galactosidase reporter gene under the control of a 3.8 kilobase fragment of the tTG promoter was characterised. The transgene construct was shown to be expressed in the apoptotic regions of the mouse embryo. Here we report that the regulation of the transgene is also apoptosis-linked in adult animals. The transgene is induced in endocrine apoptosis involving mammary gland involution and corpus luteum regression. Induction of the reporter gene is detectable during in vivo but not in vitro apoptosis of thymocytes induced by the glucocorticoid receptor, the nur77, p53 and the retinoid receptor gamma mediated pathways. Additionally, the lacZ expression mimics the activation of the endogenous promoter in tissues characterised by high apoptotic turnover. These results suggest that the apoptosis-specific transcriptional regulation of tTG is mediated through elements of a 3.8 kb promoter and may require cosignals available only in tissue environment. Cell Death and Differentiation (2000) 7, 1225 - 1233.

Animals↗
PubMed2000

Investigation of gastroprotective compounds at subcellular level in isolated gastric mucosal cells.

We tested the hypothesis that recognized gastroprotective agents exert direct protection against ethanol-induced injury in isolated rat gastric mucosal cells in vitro. If protection exists, we also wanted to identify subcellular targets in the reversible and/or irreversible stages of cell injury. Ethanol-induced cell injury was quantified by measuring plasma membrane leakage (trypan blue exclusion and lactate dehydrogenase release), mitochondrial integrity (succinic dehydrogenase), and nuclear damage (ethidium bromide-DNA fluorescence). Initial cell viability and responsiveness were estimated by the effects of carbachol, carbachol + atropine, or 16,16-dimethyl-PGE(2) on chief cell pepsinogen secretion. Enriched parietal cells were stimulated by histamine, carbachol, or histamine + IBMX. Preincubation of cells with PG, sucrose octasulfate, or the sulfhydryl compounds N-acetylcysteine, taurine, or cysteamine increased cell resistance </=21% against ethanol. Similar protection was found with low histamine concentrations, but a higher concentration aggravated ethanol toxicity. Other naturally occurring or synthetic gastroprotective agents offered partial protection or aggravated ethanol-induced cell injury. Only a few in vivo gastroprotective agents demonstrated in vitro direct cytoprotection, which involved mainly the reversible stage of cell injury (e.g., plasma membrane changes) and, less often, irreversible (e.g., mitochondrial and nuclear) damage. Our findings also indicate that a major part of the beneficial effect of gastroprotective agents is expressed at the tissue level.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Epidemiology and clinicopathology of aortic dissection.

STUDY OBJECTIVES: To determine the incidence and mortality as well as to analyze the clinical and pathologic changes of aortic dissection. DESIGN AND SETTING: A population-based longitudinal study over 27 years on a study population of 106,500, including 66 hospitalized and 18 nonhospitalized consecutively observed patients. MEASURES: Analysis of data from the medical, surgical, and autopsy records of patients with aortic dissection. RESULTS: Altogether, 86 cases of aortic dissection were found in 84 patients, corresponding to a 2.9/100,000/yr incidence. Sixty-six of the 84 patients (79%) were admitted to the hospital, and 18 patients (21%) died before admission. Their ages ranged from 36 to 97 years, with a mean of 65. 7 years. The male/female ratio was 1.55 to 1. A total of 22.7% of the hospitalized patients died within the first 6 h, 33.3% within 12 h, 50% within 24 h, and 68.2% within the first 2 days after admission. Six patients were operated on, with a perioperative mortality of two of six patients and a 5-year survival of two of six patients. All patients who were not operated on died. Pain was the most frequent initial symptom. Every patient had some kind of cardiovascular and respiratory sign. Neurologic symptoms occurred in 28 of 66 patients (42%). Five patients presented with clinical pictures of acute abdomen and two with acute renal failure. Trunk arteries were affected in 33 of the 80 autopsied cases (41%), and rupture of aorta was seen in 69 cases (86%). In five cases, spontaneous healing of dissection was also found. The ratio of proximal/distal dissections was 5.1 to 1. All 18 prehospital cases were acute. Fifty-nine cases (89.4%) were acute at admission, and 7 cases (10.6%) were chronic dissections. Hypertension and advanced age were the major predisposing factors. CONCLUSION: Aortic dissection was the initial clinical impression in only 13 of the 84 patients (15%). Thus, 85% of the patients did not receive immediate appropriate medical treatment. For this reason, these late-recognized and/or unrecognized cases may be regarded as an untreated or symptomatically treated group, whose course may resemble the natural course of aortic dissection.

Adult↗
PubMed2000

Transcriptional repression by nuclear receptors: mechanisms and role in disease.

Co-repressor proteins mediate transcriptional repression by nuclear receptors in the absence of ligand. The identification of a co-repressor-receptor interaction motif, and the finding that co-repressors and co-activators compete for the same site on the receptor, suggests a simple mechanism for the switch from repression to activation upon ligand binding. Defects in this mechanism result in dominant-negative receptors that repress transcription. Such receptors have been implicated in several clinically important diseases, including thyroid hormone resistance and diabetes mellitus.

Amino Acid Sequence↗
PubMed2000

[Tin compounds in pharmacy and nutrition].

The occurrence of tin in plants, animals and humans is discussed, in relation to its abundance in the lithosphere and hydrosphere and the range of the different tin(II) and tin(IV) complexes formed. A reasoned consideration of its essentiality for living species is provided. It is concluded that tin is beneficial, even if not yet proved to be an essential element. After reference to the chemistry of tin compounds, there is a detailed discussion of their toxicity in animals and humans. Feasible routes for tin intake and uptake into humans are described. The past and current use of tin pharmaceuticals is reviewed and the areas for which they are currently permitted for use in humans as dentifrices and mouth washes, as radio-pharmaceuticals and for the treatment of jaundiced newborns are described. A detailed review of tin-containing antitumour agents as representative tin pharmaceuticals is also given. Finally, a list of tin-containing drugs and drug candidates is also shown.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Mechanism of corepressor binding and release from nuclear hormone receptors.

The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies have identified a universal motif in coactivator proteins that mediates association with receptor LBDs. We report here the identity of complementary acting signature motifs in SMRT and N-CoR that are sufficient for receptor binding and ligand-induced release. Interestingly, the motif contains a hydrophobic core (PhixxPhiPhi) similar to that found in NR coactivators. Surprisingly, mutations in the amino acids that directly participate in coactivator binding disrupt the corepressor association. These results indicate a direct mechanistic link between activation and repression via competition for a common or at least partially overlapping binding site.

Amino Acid Sequence↗
PubMed1999

Effects of nitrogen and phosphorus fertilization in a lowland evergreen rainforest.

A nutrient addition experiment was set up in August 1993 in a species-rich primary lowland dipterocarp forest in Barito Ulu, Central Kalimantan, Indonesia. The following treatments were applied: control, +N, +P and +NP. There were five blocks of four 50 m x 50 m plots with a separate treatment for each plot. Fine litterfall was measured on all the plots from 1 May 1994 for 12 months. Litterfall mass and phosphorus concentrations were significantly higher in all the fertilizer treatments compared with the controls. All trees (> or = 10 cm dbh) were measured in August 1993 and in August 1998, and there was no significant girth increment response to fertilization in dipterocarps or non-dipterocarps. Dipterocarps of the red meranti group showed a doubling of girth increment in the +NP treatment, however, the difference from the control fell short of significance.

Ecosystem↗