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Biomedical subjects

G Lázár

Publications and source records attributed to G Lázár.

At least 19 recordsLinked to original sources

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.

OBJECTIVE AND DESIGN: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model. MATERIALS AND SUBJECTS: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0-16-grade Geisinger scoring scale. RESULTS: Acid exposure was followed by a significant decrease in the level of beta-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased beta-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant beta-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone. CONCLUSIONS: The acid-induced transcriptional level downregulation of mucosal beta-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.

ATP Synthetase Complexes↗

Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells. The mossy fiber bundle was labeled in the hilus as well as along the entire CA3 area of Ammon's horn. In the human, CART-immunoreactive mossy cells displayed the characteristic thorny excrescences both on their somata and their main dendrites. Axon collaterals of mossy cells could be seen in the hilus and the main axons formed a dense band in the inner molecular layer of the dentate gyrus, suggesting that mossy cells are the principal source of the associational pathway. Granule cells of the dentate gyrus and pyramidal neurons of the human hippocampal formation were devoid of CART peptide immunoreactivity. A few labeled non-pyramidal cells and a large group of strongly immunostained axons of unknown origin were present in all layers of CA1-3. Granule cells are the main excitatory cell population of the dentate gyrus while mossy cells are in a key position in controlling activity of granule cells. The specific location of CART peptide in the dentate granule cells of rodents and in the mossy cells of the human hippocampus may indicate involvement of neuronal circuitry of the dentate gyrus in the memory-related effects of cocaine and amphetamine. Independently of its functional role, CART peptide can be used as a specific marker of human mossy cells and of the dentate associational pathway. The sensitivity of CART peptide to postmortem autolysis may restrict the use of this marker in surgically removed hippocampi or in human brains removed and fixed shortly after death.

Adult↗

The role of the glucocorticoid-dependent mechanism in the progression of sodium taurocholate-induced acute pancreatitis in the rat.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements, and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations, and histology. In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity, and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Acute Disease↗

Microcirculatory changes in the canine oesophageal mucosa during experimental reflux oesophagitis: comparison of the effects of acid and bile.

BACKGROUND: The response of the oesophageal microcirculation to luminal damaging agents may play an important role in reflux-induced mucosal injury. We characterized the microcirculatory consequences of exposure to bile with or without hydrochloric acid, and determined the changes in the constitutive nitric oxide synthase and inducible nitric oxide synthase activities in a canine model of acute reflux oesophagitis. METHODS: Group 1 served as a saline-treated control, while groups 2-4 were exposed for 3 h to bile alone, to hydrochloric acid, or to bile + hydrochloric acid, respectively. The mucosal microcirculation was observed continuously by means of intravital videomicroscopy with an orthogonal polarization spectral imaging technique. Myeloperoxidase, constitutive and inducible nitric oxide synthase activities were measured via tissue biopsies, while the degree of mucosal damage was evaluated histologically. RESULTS: Bile evoked deep tissue damage and leucocyte accumulation in the mucosa and muscle layer. The capillary red blood cell velocity and the relative vessel area increased significantly (P < 0.05). The constitutive NO synthase activity was decreased, and the inducible NO synthase activity was increased significantly. In the hydrochloric acid-treated group the functional capillary density decreased, the mucosal damage was less severe, the constitutive NO synthase activity did not change, whereas the inducible NO synthase activity was increased significantly. The constitutive NO synthase activity did not change after the bile + hydrochloric acid treatment either. CONCLUSION: Reflux components induce characteristic microcirculatory alterations. The structural damage and leucocyte invasion are accompanied by bile-induced constitutive NO synthase inhibition when hydrochloric acid production is suppressed.

Acute Disease↗

Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice.

OBJECTIVE AND DESIGN: The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice. MATERIAL OR SUBJECTS: 159 male Wistar rats. TREATMENT: Obstructive jaundice was induced by bile duct ligation (BDL). Gadolinium chloride (1 mg/100 g iv) was given 6 days after BDL to inhibit Kupffer cell activity and the animals were challenged with 1 microg/g endotoxin 24 h later. METHODS: Endotoxin sensitivity, tumor necrosis factor-alpha and interleukin-6 production were studied, liver and lung injury were assessed by neutrophil infiltration assay, tissue adenosine triphosphate, aspartate aminotransferase, alanine aminotransferase level determinations and histology, respectively. For statistics non-parametric methods were used. RESULTS: BDL sensitized the animals to endotoxin, increased endotoxin-induced tumor necrosis factor-alpha and interleukin-6 production and reduced ATP contents of the liver and the lung. Kupffer cell blockade significantly increased the resistance against endotoxin, diminished the inflammatory cytokine release and reduced endotoxin-induced tissue injury in BDL animals. CONCLUSION: Attenuation of Kupffer cell function decreases endotoxin-induced lethality and morbidity in obstructive jaundice.

Adenosine Triphosphate↗

Peptides in frog brain areas processing visual information.

Vision is the most important sensory modality to anurans and a great deal of work in terms of hodological, physiological, and behavioral studies has been devoted to the visual system. The aim of this account is to survey data about the distribution of peptides in primary (lateral geniculate complex, pretectum, tectum) and secondary (striatum, anterodorsal and anteroventral tegmental nuclei, isthmic nucleus) visual relay centers. The emphasis is on general traits but interspecies variations are also noted. The smallest amount of peptide-containing neuronal elements was found in the lateral geniculate complex, where primarily nerve fibers showed immunostaining. All peptides found in the lateral geniculate complex, except two, occurred in the pretectum together with four other peptides. A large number of neurons showing intense neuropeptide thyrosine-like immunoreactivity was characteristic here. The mesencephalic tectum was the richest in peptide-like immunoreactive neuronal elements. Almost all peptides investigated were present mainly in fibers, but 9 peptides were found also in cells. The immunoreactive fibers show a complicated overlapping laminar arrangement. Cholecystokinin octapeptide, enkephalins, neuropeptide tyrosine, and substance P (not discussed here) gave the most prominent immunoreactivity. Several peptides also occur in the tectum of fishes, reptiles, birds, and mammals. Peptides in various combinations were found in the striatum, the anterodorsal- and anteroventral tegmental nucleus, and the isthmic nucleus that receive projections from the primary visual centers. The functional significance of peptides in visual information processing is not known. The only exception is neuropeptide tyrosine, which was found to be inhibitory on retinotectal synapses.

Afferent Pathways↗

Rapid activation of microglial cells by hypoxia, kainic acid, and potassium ions in slice preparations of the rat hippocampus.

Microglial activation induced by hypoxia, kainic acid and elevated potassium concentration, all of which alter neuronal function, was studied in hippocampal slices. The activation of microglia was detected by immunostaining with a monoclonal antibody (OX-42) raised against a type 3 complement receptor (CD11b). During activation the phenotype of microglia changes and the intensity of staining of individual cells increases. Oxygen deprivation depressed the focal responses of CA1 neurons to stratum radiatum volleys. Microglial activation was time dependent. Ten minute hypoxia caused mild activation, and after 20 min, a strong microglial reaction could be observed. Although neuronal function returned during reoxygenation, the morphological signs of microglial activation remained. Epileptiform activity of hippocampal neurons, followed by depression, was induced by application of 0.5 mM kainic acid, in a time and dose dependent manner. Washing out kainic acid did not alter microglial reaction. Elevated concentrations of potassium ions induced microglial changes similar to those induced by hypoxia and kainic acid. It is therefore suggested that an elevated extracellular potassium ion concentration may be the common factor in microglial activation observed in these experiments since this is raised both in hypoxia and under the effect of excitotoxins.

Action Potentials↗

Colocalization of GABA, enkephalin and neuropeptide Y in the tectum of the green frog Rana esculenta.

The colocalization of GABA, enkephalin and neuropeptide Y immunoreactivity in neurons in the pretectal area and in the mesencephalic tectum of the green frog (Rana esculenta) was studied. Several Met-enkephalin immunoreactive perikarya were found in layer 6 of the tectum and every third of these neurons showed GABA-ir as well. Colocalization of GABA and NPY could also be shown in half of the neuropeptide Y immunopositive cells in the 6th layer of the tectum, but only a few cells were double stained in layers 9 and 4. In the pretectal area no colocalization of the investigated peptides and GABA was found.

Animals↗

Brain phagocytes may empty tissue debris into capillaries.

The possibility that brain phagocytes may empty remnants of degenerated neurons into capillaries has been studied in frogs. Degeneration of nerve fibers was brought about by transectioning the optic tract, the tectothalamic and tectoisthmic tracts, the postoptic commissure or the radial nerve. To help identification of phagocytozed degenerated neuronal elements, the transected fibers were filled either with horseradish peroxidase (HRP) or cobaltous-lysine complex. The survival times were 3, 4, 7, 27, 47 and 70 days after the application of the markers. The HRP-labeled structures were identified in 60 microm thick sections using diaminobenzidine as chromogen, while cobalt was precipitated in the form of cobaltous sulfide. Small pieces of these sections were further processed for electron microscopy. In each area of the brain and spinal cord investigated, microglial cells and astrocytic processes containing fragments of degenerated neuronal elements could be seen close to capillaries. In some cases a microglial or astrocytic process pierced the capillary basal lamina and seemingly delivered inclusion bodies into the cytoplasm of capillary endothelial cells and pericytes. In the inclusion bodies, which were usually large vesicles, fragments of HRP or cobalt-labeled or unlabeled membranes with a foamy appearance, or condensed myelin lamellae could be observed. These vesicles protruded the luminal membrane of the endothelial cell that was disrupted in some cases suggesting that the content of the inclusion body was discharged into the lumen of the capillary. These results give support to Penfield's hypothesis (1925) that glial cells may empty phagocytozed materials into capillaries.

Animals↗

Bile-induced adenosine triphosphate depletion and mucosal damage during reflux esophagitis.

BACKGROUND: This study was designed to investigate the role of bile in a large animal model of acute esophageal reflux disease. METHODS: An agar electrode was used to measure the transmucosal potential difference of the esophagus in anaesthetized dogs. The vascular permeability index and the epithelial permeability index of the mucosa were evaluated by means of the Evans blue and the sodium-fluorescein clearance method, respectively. The tissue adenosine triphosphate (ATP) level and the myeloperoxidase activity were determined from tissue biopsies, while the degree of mucosal damage was evaluated histologically on a grade 0-100 scale. Group 1 (n = 8) served as saline-treated control; groups 2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed for 4 h to canine bile alone, to hydrochloric acid + bile, or to hydrochloric acid alone, respectively. RESULTS: In Groups 2, 3 and 4 the degree of mucosal damage was significantly increased, and a 4-fold elevation in myeloperoxidase activity was observed. The transmucosal potential difference was decreased significantly below the control level, while the vascular and epithelial permeability indices were significantly increased compared with the control values. Bile, but not hydrochloric acid, evoked a significant (40%) decrease in the ATP level of the esophageal tissue. CONCLUSIONS: We propose that mucosal dysfunction, structural damage and leukocyte invasion during hydrochloric acid-induced esophageal injury are exacerbated by bile-induced changes in tissue ATP concentrations during experimental esophageal reflux disease.

Acute Disease↗

[Surgical treatment of Boerhaave's syndrome].

The authors treated four patients with spontaneous oesophageal rupture between 1995 and 1999. The interval from injury to surgical treatment was less than 24 h in two cases, and longer than 24 h in the other two cases. The surgical treatment was primary closure of the rupture and mediastinal drainage with gastrostomy within 24 h after the onset. Septic complications occurred in lately presented patients. In these cases, the surgical treatment consisted of oesophagectomy, mediastinal drainage and feeding gastrostomy. The alimentary tract was reconstructed with interposed ileocolon eight weeks later. Each patients was fully recovered. The authors underline the importance of early diagnosis which obviously determine the prognosis and the choice of surgical treatment. Primary repair is proposed after early diagnosis, however oesophageal resection is recommended 24 h after the injury.

Adult↗

Early microglial reaction following mild forebrain ischemia induced by common carotid artery occlusion in rats.

Early microglial reaction following mild ischemic injury caused by bilateral common carotid artery occlusion has been investigated in rats. The ischemic insults lasted for 10, 15 and 20 min without recirculation, and with several reperfusion intervals from 1 h to 3 days. The resting and activated microglial cells were visualized with immunohistochemistry using monoclonal antibodies raised against the CR3 complement receptor, the MHC class I and class II antigens, the macrophage common antigen and with Bandeiiraea simplicifolia lectin-histochemistry. The neuroprotective effect of hypothermia on the early microglial activation was also studied. Ten minutes bilateral common carotid artery occlusion in hypothermic rats without reperfusion caused a mild microglial reaction in the hippocampus. Strong reaction was seen following 20 min insult without reperfusion. Ischemia followed by recirculation caused milder reaction than without reperfusion. Our results suggest that the microglial cells are very sensitive indicators of a mild, transient ischemic insult that does not result in neuronal cell death.

Animals↗

[Minimally invasive adrenalectomy with posterior retroperitoneoscopy].

Authors report a total of 14 adrenalectomies performed from a posterior (lumbotomy) approach, using minimally invasive retroperitoneoscopic technique. The "UltraCision" scalpel, an ultrasound activated cutter-coagulation device has been used for operative tissue dissection. Two cases were converted. The mean operating time of the successful 12 cases were 128 minutes. No mortality and no septic complication occurred. The mean operative blood loss of the 12 procedures were less than 100 ml. The mean hospitalisation was 3-5 days, and the complete recovery needed 2-3 weeks. On the basis of our own experiences and the ones of prospective, randomized clinical studies of the literature, the retroperitoneoscopic adrenalectomy from a posterior approach is recommended for the surgical treatment of benign tumours of the suprarenal gland with a size less than 5 cm diameter. The low conversion- and complication-rate, the minimal operative blood loss, the short hospitalization and quick recovery time all are the advantages of this method. It can be performed after previous abdominal operation and in cases with morbid obesity. The technique is suitable for bilateral adrenalectomies as well. This method is not justified for the removal of malignant and/or larger than 5 cm adrenal tumours. Coagulopathies are contraindications.

Adrenalectomy↗

[Total mesorectal excision with ultrasonic coagulation knife ("UltraCision") in surgery of rectal cancer].

The authors report a total of 62 middle and low third rectal cancer cases operated on by total mesorectal excision by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The total mesorectal excision facilitates, the low anterior resections and preservation of sphincter with an ultra-low colorectal, or coloanal anastomosis using the double stapling technique. In the authors' experience, the "UltraCision" cutting-coagulating device permits an atraumatic, bloodless and oncologically correct dissection. Using the double stapling technique, we succeeded in 60% of our middle- and low-third rectal cancer patients to perform a sphincter preserving low anterior resection. In 9 (28%) of the low third rectal cancer patients, preservation of the sphincter was possible with oncologically correct anterior resection and an ultra-low colo-anal anastomosis. Three anastomotic insufficiencies occurred, two of them healed on lotion-suction drainage, and one on the application of transient protective ileostomy. The literature data suggest a lower local recurrency rate after radical rectal cancer surgery, if total mesorectal excision is performed.

Adult↗

Developmental changes of NADPH-diaphorase positive structures in the isthmic nuclei of the chick.

Nicotine adenine dinucleotide phosphate-diaphorase staining was used to study nitric oxide synthase activity and distribution in the midbrain visual structures of white leghorn chick embryos and post-hatched chickens. Enzyme staining first appeared in the isthmic region at the tenth embryonic day (E10) in the neuropil of the nucleus isthmi, pars parvocellularis. At E11 faint enzyme positivity appeared also in the nucl. isthmi pars magnocellularis, the nucl. semilunaris and the nucl. isthmo-opticus. The staining intensity of the isthmic nuclei dramatically increased between the 12.5th and the 13th days of incubation. The nucl. isthmi, pars parvocellularis showed the strongest enzyme reaction throughout embryonic life. A day before hatching all the isthmic nuclei were heavily stained, however, nicotine adenine dinucleotide phosphate-diaphorase-positive cells occurred exclusively in the nucleus isthmo-opticus. In the tectum opticum, intensely stained cells occupied the stratum fibrosum et griseum superficiale. The layer containing the projection neurons to the isthmo-optic nucleus was unstained. In the isthmic region, the intensity of staining surpassed that of the tectum and reached its maximum at E17 and then slowly decreased till the end of the experimental period (120 days post-hatched). The tractus isthmo-opticus showed nicotine adenine dinucleotide phosphate-diaphorase activity throughout the investigated period of life of the chicken, but the tractus tectoisthmo-opticus was unstained. Our results suggest that in the isthmic nuclei, nicotine adenine dinucleotide phosphate-diaphorase-positive neurons occur only in the isthmo-optic nucleus and optic tectum. The other positively stained structures are the fibers and terminals of tectal cells. In most brain areas nicotine adenine dinucleotide phosphate-diaphorase indicates nitric oxide synthase that produces nitric oxide. The transient appearance of this molecule is probably necessary for neuronal differentiation or the establishment of synaptic connections in the isthmic nuclei, and these developmental changes are under the control of the optic tectum.

Age Factors↗

The effect of the glucocorticoid Oradexon on endotoxin-induced peritoneal cell response.

Glucocorticoids are important modulators of immune reactions. They are capable of antagonising several effects of the bacterial endotoxin by inhibiting endotoxin-induced leukocyte activation, and the production of cytokines and inflammatory mediators. We earlier demonstrated that the antiglucocorticoid RU 38486 enhances the cytokine production induced by endotoxin and aggravates the course of experimental endotoxic and septic shock. In the present study we investigated the effect of the glucocorticoid Oradexon on the endotoxin-induced peritoneal cell response. For measurement of the peritoneal cell response, male CFLP mice (20-25 g) were injected i.p. with 10 microg/10 g body weight endotoxin (E. coli 026:B6 LPS, Difco Lab, Detroit, lot 110273JB). Dexamethasone (Oradexon, N.V, Organon Oss, The Netherlands) was administered i.p., i.v. or s.c. in a dose of 0.1 mg/10 g body weight, alone or concomitantly with endotoxin. We found that bacterial endotoxin increased the total cell count due to neutrophilia at 24 hours and, due to increases in the number of macrophages and lymphocytes 48 and 72 hours after treatment, respectively. The i.p., i.v., and s.c. injection of Oradexon, increased the total cell count and the macrophage count at 24, 48 and 72 hours. The i.p., s.c. and i.v. injection of Oradexon, concomitantly with endotoxin, reduced the total cell count at 48 and 72 hours, due to decreases in the macrophage count. The i.p., i.v. or s.c. administration of Oradexon concomitantly with LPS decreased the lymphocyte count and the neutrophil count at 24 and 72 hours. These results prove that glucocorticoids are capable of modifying the immune cell reactions induced by endotoxin.

Animals↗

Extra-abdominal desmoid mimicking malignant male breast tumor.

A rare case of extra-abdominal desmoid tumor is reported. A palpable mass was detected in the right breast of a 47-year-old man. Mammography showed a stellate mass without calcification, and breast ultrasound examination revealed a solid, inhomogeneous, non-calcified lesion. The result of cytological examination of the fine-needle aspiration biopsy specimen was equivocal. Histology of the surgical specimen showed extra-abdominal desmoid tumor. Extra-abdominal presentation of this semimalignant tumor is rare and may mimic malignant breast tumor. Differential diagnosis is difficult and usually based on the result of the histological examination.

Biopsy, Needle↗