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G Farkas

Publications and source records attributed to G Farkas.

At least 55 records · Page 3Linked to original sources
PubMed1996

The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division.

The GAGA protein of Drosophila was first identified as a stimulatory factor in in vitro transcription assays using the engrailed and Ultrabithorax promoters. Subsequent studies have suggested that the GAGA factor promotes transcription by blocking the repressive effects of histones; moreover, it has been shown to function in chromatin remodeling, acting together with other factors in the formation of nuclease hypersensitive sites in vitro. The GAGA factor is encoded by the Trithorax-like locus and in the studies reported here we have used the maternal effect allele Trl13C to examine the functions of the protein during embryogenesis. We find that GAGA is required for the proper expression of a variety of developmental loci that contain GAGA binding sites in their upstream regulatory regions. The observed disruptions in gene expression are consistent with those expected for a factor involved in chromatin remodeling. In addition to facilitating gene expression, the GAGA factor appears to have a more global role in chromosome structure and function. This is suggested by the spectrum of nuclear cleavage cycle defects observed in Trl13C embryos. These defects include asynchrony in the cleavage cycles, failure in chromosome condensation, abnormal chromosome segregation and chromosome fragmentation. These defects are likely to be related to the association of the GAGA protein with heterochromatic satellite sequences which is observed throughout the cell cycle.

Animals↗
PubMed1996

Cytokine level changes in L-arginine-induced acute pancreatitis in rat.

The role of different cytokines in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, and the ability of KSG-504, a novel cholecystokinin receptor antagonist, to exert protection in this type of acute pancreatitis was evaluated. Male Wistar rats received 250 mg/100 g body weight of Arg intraperitoneally twice, at an interval of 1 h. Control rats received instead the same amount of glycine at the same times. Fifty mg/kg KSG-504 was injected subcutaneously 0.5 h before and 6, 18 and 36 h after the first Arg administration. Rats were examined 12, 24 and 48 h after pancreatitis induction. To assess the severity of inflammation, the edema was quantified, the serum amylase level was measured, and histologic examinations were performed. Serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In Arg-induced acute pancreatitis, the amylase level was increased significantly at 12 h (48.600 +/- 3.980 U/l) and 24 h (30.800 +/- 3.813 U/l) vs. the control group (6.382 +/- 184 U/l). No significant alteration in the ratio pancreatic weight/body weight was found in the different groups. However, in Arg-induced acute pancreatitis, both the TNF-alpha (15.1 +/- 6.9 U/ml) and the IL-6 (39.6 +/- 19.2 pg/ml) levels were already elevated significantly at 12 h vs. the controls (3.1 +/- 0.8 U/ml and 15.2 +/- 3.1 pg/ml, respectively) and remained elevated at 24 and 48 h. Simultaneous KSG-504 administration did not modify the measured cytokine levels. No significant changes in plasma CCK levels were observed. In Arg-induced acute pancreatitis, histological evaluation revealed diffuse but microfocal necrobiotic alterations. No marked protective effects of KSG-504 were observed on histological sections. These results suggest that excessive doses of Arg induce severe acute pancreatitis in rat, with a simultaneous cytokine level elevation. Endogenous CCK does not seem to play an essential role in the pathogenesis of Arg-induced acute pancreatitis.

Acute Disease↗
PubMed1995

[Cranioplasty using computer-designed implants (preliminary report)].

The co-operation among plastic surgeons and computer experts is presented demonstrating the reconstruction of a cranial bone defect of a patient. The adequacy of manufactured implant for reconstruction of cranial bone defect on the base of classic methods in only approximate. Computer aided design is needed for creating a more sophisticated implant. Cranial CT is digitised and a 3 dimensional model is created. The precise implant, manufactured by a computer directed milling machine, fits ino the bone defect. During the operation the cranial bone defect is explored, the bone edges are identified. The implant is fixed and the skull skin is closed. The authors demonstrate a successful operation of a cranial bone defect of 9 x 6.7 cm, the complicated shape and bone surface was reconstructed by a computer aided and manufactured implant. The co-operation of plastic surgeon and computer experts are essential during the process of implant design. The computer assisted and manufactured implants are suitable for the most sophisticated functional and aesthetic reconstruction of bone defect with complicated surface and irregular pattern.

Adult↗
PubMed1995

[Inflammatory mediators in acute pancreatitis (theoretical considerations)].

Cytokines are important immunoregulatory mediators. Their contribution to the pathogenesis of acute and chronic gastroenterological disorders is obvious. Increased expression of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) can be detected in inflammatory bowel disease. During the last few years it has also been recognized that activated leukocytes have an important role in the multisystem involvement of acute pancreatitis. Activation of leukocytes is an early event during severe acute pancreatitis, and it may be a pathogenetic factor in the severity of the disease. The review summarizes the recent findings in the field of inflammatory cytokines with particular attention of TNF, IL-1, IL-6, and IL-8 during severe acute pancreatitis and underscores the role of the activated leukocytes in the pathogenesis of complicated acute pancreatitis.

Acute Disease↗
PubMed1995

[Management of septic complications od acute necrotizing pancreatitis].

The authors present the case of a 47 year old male patient with acute necrotizing pancreatitis complicated with widespread mesenteric necrosis and abscess. The critically ill patient (APACHE score: 28.5) underwent on seven operations and required 50 days of intensive care. The authors analyse the conditions of successful treatment and emphasize the importance of new available therapeutic approaches and instruments.

APACHE↗
PubMed1995

Successful simultaneous transplantation of kidney and fetal pancreatic islet masses.

This paper reports our experience with the successful simultaneous transplantation of kidney and fetal pancreatic islets in 46-year-old diabetic man. No detectable C-peptide level was noted and the end-stage nephropathy required hemodialysis. The cadaver kidney and two masses of 8-week-cultured fetal islets were grafted simultaneously. After revascularization of the kidney, the islet masses were placed under the kidney capsule. Following transplantation, islet function was demonstrated by a higher C-peptide level, which subsequently persisted. Twenty-four months after grafting, islet function was provoked by glucagon and glucose, which led to elevations in the C-peptide and insulin levels. The insulin requirement fell from 58 to 24 U/day during the post-transplant period of 24 months. The mean value of HbA1C (5.6% +/- 0.3%) indicated a constantly normal carbohydrate metabolism. Improvements in retinopathy were also noted. Three periods of kidney rejection were diagnosed, but these proved reversible with high-dose steroid treatment. The serum and urine beta-2-microglobulin levels correlated well with rejection and recovery. More than 2 years after grafting, kidney functions is in the normal range. On sonography, the transplanted islet masses were repeatedly clearly visible, and 24 months following transplantation the volume was twice the original one. The results indicate that simultaneous kidney and fetal pancreatic islet grafting is advantageous in end-stage nephropathy secondary to type I diabetes mellitus.

C-Peptide↗
PubMed1995

Inhibition of tumor necrosis factor production and ICAM-1 expression by pentoxifylline: beneficial effects in sepsis syndrome.

Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and septic shock. Suppression of its biosynthesis might therefore be one of the strategies in the treatment of sepsis. When peripheral white blood cells were stimulated with either E. coli lipopolysaccharide (LPS) or Staphylococcus aureus, pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate inhibitory effect was observed on the induction of interleukin 6 (IL-6). PTX inhibited not only the TNF production of monocytes, but also the TNF secretion of both granulocytes and unseparated whole blood. The in vitro TNF and IL-6 producing capacities were higher in septic patients (n = 31) than in healthy blood donors (n = 15). Administration of PTX (400 mg/day) to 20 of the septic patients resulted in TNF production similar to that found in healthy controls. It also subsequently led to an improvement of the clinical status classified by the APACHE II score. The soluble intercellular adhesion molecule-1 (sICAM-1) level was significantly higher in the sera of septic patients before PTX treatment (800-1200 ng/ml) than in normal individuals (50-150 ng/ml), but it decreased following PTX therapy. Cytofluorometric analysis revealed that the expression of ICAM-1 on stimulated mononuclear cells was inhibited by PTX. It is presumed that the suppressive effect of pentoxifylline on TNF production may be of clinical importance, improving the therapeutic strategies in septic syndrome.

Adult↗
PubMed1995

Effects of pentoxifyllin and PentaglobinO on TNF and IL-6 production in septic patients.

Pentoxifylline inhibited the TNF production of purified human white blood cells and whole blood cultures stimulated either by LPS or by Staphylococcus aureus. PTX did not influence the CD14 expression. The in vitro TNF and IL-6-producing capacities of septic patients were higher than in the control group. Administration of PTX to septic patients resulted in the normalization of TNF synthesis and in a moderate decrease in IL-6 production. It also subsequently led to an improvement in the clinical status. A further improvement in APACHE II score could be achieved by administration of PentaglobinO (Biotest). The prevention of in vitro TNF production by PentaglobinO could be demonstrated involving the use of whole blood rather than purified lymphocytes. The level of soluble ICAM-1 in the serum of septic patients was significantly higher than in normal individuals, but it decreased following PTX and PentaglobinO therapy. It is presumed that PTX and PentaglobinO can antagonize cytokine production at different levels, resulting in synergistic action that is beneficial in the treatment of sepsis.

Humans↗
PubMed1994

The Trithorax-like gene encodes the Drosophila GAGA factor.

Little is known about the way higher-order chromatin structure influences gene expression and chromosome topology in general. Genetic analysis in Drosophila has led to the discovery of two classes of genes, the regulators of homeotic genes and the modifiers of position-effect variegation, which seem to be good candidates for encoding some of the factors regulating chromatin functions. The Trithorax-like gene we described here is required for the normal expression of the homeotic genes and is a modifier of position-effect variegation. We found that Trithorax-like encodes the GAGA factor which is involved in the formation of an accessible chromatin structure at promoter sequences. Our genetic analysis suggests that the chromatin modelling function of the GAGA factor is not restricted to promoter regions.

Animals↗
PubMed1994

Phosphorylation of poly(ADP-ribose)polymerase protein in human peripheral lymphocytes stimulated with phytohemagglutinin.

Intracellular phosphorylation of poly(ADP-ribose)polymerase was assayed in streptolysin-O-permeabilized human lymphocytes. Whereas 32P incorporation from [gamma-32P]ATP into immunoprecipitated enzyme protein was undetectable in resting cells, significant phosphorylation of this enzyme was observed in lymphocytes treated with phytohemagglutinin. The phosphorylation of poly(ADP-ribose)polymerase in permeabilized cells was not stimulated by phorbol ester, while phorbol-induced phosphorylation of other proteins and of a specific oligopeptide substrate of protein kinase C was observed. However, the specific inhibitory pseudosubstrate peptide of protein kinase C blocked the phosphorylation of poly(ADP-ribose)polymerase induced by phytohemagglutinin. Therefore, a potential role of a member of the protein kinase C family in the phytohemagglutinin stimulated intracellular phosphorylation of poly(ADP-ribose)polymerase is conceivable.

Bacterial Proteins↗
PubMed1994

Lipocortin I is not accessible for protein kinase C bound to the cytoplasmic surface of the plasma membrane in streptolysin-O-permeabilized pig granulocytes.

We previously observed a 38 kDa protein that was a major protein component of the cytosolic extract of pig granulocytes and the dominant substrate of protein kinase C at supra-physiological Ca2+ concentrations. The purified 38 kDa protein itself required Ca2+ to be phosphorylated by protein kinase C. Now we demonstrate that this protein, which is also present in human granulocytes, is identical to lipocortin I. The identification is based on the chromatographic properties and immunoblot of the purified protein which is also a good substrate for tissue transglutaminase. Phosphorylation of lipocortin I by protein kinase C was investigated in granulocytes permeabilized with streptolysin-O. At physiological intracellular Ca2+ concentrations lipocortin I was not phosphorylated at all. At supra-physiological Ca2+ concentrations (0.5 mM), lipocortin I was also not phosphorylated when protein kinase C was translocated to the membrane by treatment of the cells with phorbol myristate acetate. Its phosphorylation was detectable only in control experiments when protein kinase C was activated in the cytosol by the addition of dioleoylglycerol and phosphatidylserine to the permeabilized cells. The data presented show that, in permeabilized granulocytes, Ca(2+)-lipocortin is not formed at physiological Ca2+ concentrations, and at supra-physiological Ca2+ concentrations the Ca(2+)-lipocortin I is not accessible to protein kinase C bound to the cytoplasmic surface of the plasma membrane.

Animals↗
PubMed1993

Displacement chromatography on cyclodextrin silicas. IV. Separation of the enantiomers of ibuprofen.

A displacement chromatographic method has been developed for the preparative separation of the enantiomers of ibuprofen using a beta-cyclodextrin silica stationary phase. The retention behavior of ibuprofen was studied in detail: the log k' vs. polar organic modifier concentration, the log k' vs. pH, the log k' vs. buffer concentration and the log k' vs. 1/T relationships; also, the alpha vs. polar organic modifier concentration, the alpha vs. pH, the alpha vs. buffer concentration and the log alpha vs. 1/T relationships have been determined in order to find the carrier solution composition which results in maximum chiral selectivity and sufficient, but not excessive solute retention (1 < k' < 30). 4-tert.-Butylcyclohexanol, a structurally similar but more retained compound than ibuprofen, was selected as displacer for the separation. Even with an alpha value as small as 1.08, good preparative chiral separations were observed both in the displacement mode and in the overloaded elution mode, up to a sample load of 0.5 mg.

Acetonitriles↗
PubMed1993

[In vitro study and clinical transplantation of human fetal islands of Langerhans].

A simple and reliable procedure was developed for the long-term culturing and cryopreservation of human fetal pancreatic islets. The methods involved can ensure the survival and the growth capacity of fetal tissue. The long-term cultivation or cryoculturing of fetal islet tissue was applied in 23 clinical transplantatious on the basis of the experimental study. All of the diabetic patients suffered progressive retinopathy and three of them had nephropathy as well. After grafting the insulin requirement reduced significantly (39.4%) correlated with the higher serum C-peptide level (mean: 0.41 ng/ml). During the long-term follow-up (9 yrs), the graft function failed in 5 cases, while in 18 successful cases the long term graft function depended on the volume of the grafted islet mass. The results suggest that the transplantation of fetal pancreatic islet has a beneficial effect in the early stage of diabetic complications.

Cryopreservation↗
PubMed1993

New patterns of bulk DNA repair in ultraviolet irradiated mouse embryo carcinoma cells following differentiation.

Mouse embryocarcinoma stem cells differentiate in culture, given the appropriate induction. We examined whether these cells could provide information about the regulation of nucleotide excision repair in relation to differentiation by measuring the rate-limiting incision step, the removal of cyclobutane dimers and (6-4) photoproducts from the genome as a whole and the effect of the bacteriophage T4 endonuclease (denV) gene on repair in differentiated cells. It was found that differentiation is accompanied by a marked decline in the early incision ability after UV irradiation (sixfold for P19, fourfold for PCC7 and twofold for F9), and we measured, in parallel, the loss of two common UV photoproducts [cyclobutane dimers and (6-4) photoproducts] from P19 cells. After differentiation, the excellent overall cyclobutane dimer repair capacity of proliferating cells (84% removal in 24 h) is lost (no removal in 24 h), while removal of (6-4) photoproducts, although normal at 24 h (94%), is much slower than in undifferentiated P19 at 3 h (no removal versus 64%). The presence of the denV gene greatly stimulates the repair of cyclobutane dimers in undifferentiated P19 cells (94% removal at 3 h versus 40%) and also in differentiated cells (50% removal at 24 h versus no removal). The denV gene also stimulates the early repair of (6-4) photoproducts in both differentiated and undifferentiated cells.

Animals↗