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Biomedical subjects

E Szabó

Publications and source records attributed to E Szabó.

At least 19 recordsLinked to original sources
PubMed2005

Curli expression of enterotoxigenic Escherichia coli.

One hundred and four enterotoxin producing Escherichia coli strains of wide geographical origin were tested for the expression of curli fimbriae by transmission electronmicroscopy and by ELISA using curli-specific antibodies, as well as for the presence of curli-specific gene sequences by PCR. All isolates, irrespective of the production of the fimbriae, carried sequences specific for the structure (csgA) and for one of the regulator genes (crl) of curli expression, respectively. Curli fimbriae were detected in 56 strains (53.8 %). Thirty-six strains expressed curli only when growing at 30 degrees C, 4 isolates were weakly curliated at 37 degrees C only, while on 16 strains curli was observed at both temperatures. On isolates carrying curli at both temperatures the expression of the fimbria was significantly stronger at 30 degrees C than at 37 degrees C. Curli proficiency significantly, but not completely, correlated with the binding of the Congo Red dye. The expression of curli did not confer epithelial cell invasiveness to ETEC strains but, once expressed at 30 degrees C, it facilitated the adherence of the bacteria to plastic surfaces. Curli present in more than half of the ETEC strains and expressed preferentially at low temperatures could be a factor facilitating the environmental survival of this food- and water-borne pathogen.

Bacterial Adhesion↗
PubMed2004

Effect of PACAP on LH release studied by cell immunoblot assay depends on the gender, on the time of day and in female rats on the day of the estrous cycle.

We have previously demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) can be released from cultured rat anterior pituitary cells and when added to the medium in physiological concentration it releases LH from individual gonadotropes. In the present work, we studied whether the release of PACAP and the responsiveness of LH cells to PACAP depend on the gender, on the time of day when the animals were sacrificed, and in females on the stage of the estrous cycle. Anterior pituitary cells were cultured on nitrocellulose membrane. We found that the number of PACAP releasing cells was higher in proestrous than in diestrous female or in male rats and their number was always higher in the evening than at the other times. The effect of PACAP on LH cells was stimulatory in the morning of proestrus and diestrus. In proestrous rats, PACAP did not influence LH release in the afternoon or the evening, but in diestrous rats it decreased it in the afternoon and the evening. In males, there was a decrease of LH due to PACAP treatment at 10 and 20 h; however, PACAP did not influence LH at 16 h. It was concluded that in vivo PACAP might be involved in the circadian and episodic release of LH at pituitary level.

Animals↗
PubMed2002

Cell immunoblot assay study demonstrating the release of PACAP from individual anterior pituitary cells of rats and the effect of PACAP on LH release.

The presence of pituitary adenylate cyclase activating polypeptide (PACAP) was previously demonstrated in the anterior pituitary by radioimmunoassay, immunohistochemistry, and reverse transcript-polymerase chain reaction (RT-PCR). With the use of cell immunoblot assay (CIBA), when the pituitary cells were cultured on nitrocellulose membrane, the release of PACAP by individual anterior pituitary cells was observed. The released peptide, trapped by the nitrocellulose membrane forming a blot around the cells, was demonstrated by immunocytochemistry. Double labeling revealed that a part of PACAP-immunoreactive cells can release LH as well. With the use of sandwich enzyme immunoassay (S-EIA), it was found that the concentration of PACAP in the anterior pituitaries is 10(-10) M. In cell culture in a similar concentration, PACAP stimulated the LH release from female gonadotropes, but did not influence it from male ones. The stimulated release of LH was indicated by the enhancement in the diameter of LH blots compared to the untreated control cultures. We concluded that PACAP may be released from the anterior pituitary cells in a concentration which would be able to influence LH release not only in vitro but under in vivo conditions as well. The effect of PACAP on LH release was different in female and male pituitary cultures.

Animals↗
PubMed2001

Partial protection by poly(ADP-ribose) polymerase inhibitors from nitroxyl-induced cytotoxity in thymocytes.

Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.

Animals↗
PubMed2001

[Uterine artery embolization for the conservative management of leiomyoma].

Uterine leiomyoma, a benign, monoclonal tumor derived from a single myometrial cell, is one of the most frequent diseases in the female reproductive system. However, the factors involved in its initiation and growth remain poorly understood. Most commonly, it results in dysmenorrhea, menorrhagia, urinary tract and neurological symptoms, and abdominal distension. Additionally, it may cause infertility, late miscarriage or other severe complications in pregnancy. The conventional treatment for fibroids has been hysterectomy. However, many women do not like to lose their uterus and potential fertility. Myomectomy and medical treatment with GnRH analogue are accepted as alternative organ-conserving methods with limited efficacy. Selective embolization of uterine arteries might therefore have a significant role in the management of the disease. The purpose of this study was to determine the effectiveness of uterine embolization as primary therapy in the management of myomas. Uterine arterial embolization was performed in 3 patients with symptomatic leiomyomas. The uterus and fibroids were objectively evaluated with ultrasound and MRI. The efficacy and safety convinced the authors that this promising technique is at present the only reasonable alternative method in organ-conserving therapy. It is less invasive than surgery, it can restore fertility, it is well tolerated and the recovery time is shorter than that following surgical procedures. This preliminary experience is sufficient to encourage gynecologists to introduce the method in Hungary.

Adult↗
PubMed2001

Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase.

OBJECTIVE AND DESIGN: Oxygen- and nitrogen-derived free radicals and oxidants play an important role in the pathogenesis of various forms of inflammation. Recent work emphasizes the importance of oxidant-induced DNA strand breakage and activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in the pathogenesis of various inflammatory diseases. We have recently demonstrated the efficacy of PJ34, a novel, potent phenanthridinone derivative PARP inhibitor, in rodent models of diabetic vascular dysfunction and stroke. Here we tested the efficacy of PARP inhibition in various models of local inflammation in rodents. MATERIALS AND METHODS: PJ34 (at doses of 0.03-30 mg/kg) was tested in rats and mice subjected to standard models of inflammation, with relevant parameters of inflammation measured using standard methods. RESULTS: PJ34 treatment (s.c, i.p. and i.v.) dose-dependently suppressed neutrophil infiltration and nitric oxide (but not KC and IL-1beta) production in peritonitis. In a model of systemic endotoxemia, PJ34 pretreatment significantly reduced plasma levels of TNF-alpha, IL-1beta and nitrite/nitrate (breakdown products of nitric oxide) production. PJ34 treatment (oral gavage) induced a significant suppression of the inflammatory response in dextran sulfate colitis, multiple low dose streptozotocin diabetes and cyclophosphamide-accelerated autoimmune diabetes in the non-obese diabetic mice, and reduced the degree of mononuclear cell infiltration into the iris in an endotoxin-induced uveitis model. Delaying the start of PJ34 administration in the colitis model conferred significant protective effects, while in the arthritis model the post-treatment paradigm lacked protective effects. CONCLUSIONS: PJ34 provides significant, dose-dependent, anti-inflammatory effects in a variety of local inflammation models. Some of its actions are maintained in the post-treatment regimen and/or after discontinuation of treatment. We conclude that PARP inhibition offers a powerful means for reducing the severity of various forms of local inflammatory responses.

Adenosine Triphosphate↗
PubMed2001

Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation.

Diabetic patients frequently suffer from retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. The loss of endothelial function precedes these vascular alterations. Here we report that activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of endothelial dysfunction in diabetes. Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation. Treatment with a novel potent PARP inhibitor, starting after the time of islet destruction, maintained normal vascular responsiveness, despite the persistence of severe hyperglycemia. Endothelial cells incubated in high glucose exhibited production of reactive nitrogen and oxygen species, consequent single-strand DNA breakage, PARP activation and associated metabolic and functional impairment. Basal and high-glucose-induced nuclear factor-kappaB activation were suppressed in the PARP-deficient cells. Our results indicate that PARP may be a novel drug target for the therapy of diabetic endothelial dysfunction.

Animals↗
PubMed2001

Peroxynitrite production, DNA breakage, and poly(ADP-ribose) polymerase activation in a mouse model of oxazolone-induced contact hypersensitivity.

Peroxynitrite-induced poly(ADP-ribose) polymerase activation has been implicated in the pathogenesis of various inflammatory conditions. Here we have investigated whether peroxynitrite and poly(ADP-ribose) polymerase may play a role in the pathophysiology of the elicitation phase of contact hypersensitivity. We have detected nitrotyrosine, DNA breakage, and poly(ADP-ribose) polymerase activation in the epidermis of mice in an oxazolone-induced contact hypersensitivity model. As tyrosine nitration is mostly mediated by peroxynitrite, a nitric-oxide-derived cytotoxic oxidant capable of causing DNA breakage, we have applied peroxynitrite directly on mouse skin and showed poly(ADP-ribose) polymerase activation in keratinocytes and in some scattered dermal cells. We have also investigated the cellular effects of peroxynitrite in HaCaT cells, a human keratinocyte cell line. We found that peroxynitrite inhibited cell proliferation and at higher concentrations also caused cytotoxicity. Peroxynitrite activates poly(ADP-ribose) polymerase in HaCaT cells and poly(ADP-ribose) polymerase activation contributes to peroxynitrite-induced cytotoxicity, as indicated by the cytoprotective effect of the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide. The cytoprotective effect of 3-aminobenzamide cannot be attributed to inhibition of apoptosis, as apoptotic parameters (caspase activation and DNA fragmentation) were not reduced in the presence of 3-aminobenzamide in peroxynitrite-treated cells. Moreover, poly(ADP-ribose) polymerase inhibition by 3-aminobenzamide dose-dependently reduced interferon-induced intercellular adhesion molecule 1 expression as well as interleukin-1beta-induced interleukin-8 expression. Our results indicate that peroxynitrite and poly(ADP-ribose) polymerase regulate keratinocyte function and death in contact hypersensitivity.

Adjuvants, Immunologic↗
PubMed2001

Thoracic core needle biopsy using ultrasound guidance.

This article demonstrates the usefulness of ultrasound (US)-guided core needle biopsy in the diagnosis of thoracic lesions. Between January 1997 and June 2000, 45 US-guided core needle biopsies were performed in the department of radiology. This method was chosen in every case when the lesion abutted the chest wall. Conventional histologic examinations supplemented by immunohistochemical methods were performed. The location and size of the mass, the number of samplings, the needle size, the histologic results, and any complications were recorded. Twenty-two lesions reached the anterior, six reached the lateral, and 14 reached the posterior chest wall. Biopsies were performed on three masses from the supraclavicular region. The mean diameter was 4.5 cm and the number of passes was 1.8; 18-G, 16-G, and 14-G needles were used in 41, two, and two cases, respectively. In 43 of the 45 cases (95.68%), an exact histologic diagnosis could be provided. In two cases, only necrotic tissue was seen in the biopsy sample. No major complications occurred. Minor complications, including pain and collaptiform weakness, were documented in four patients. Ultrasound-guided core needle biopsy of thoracic lesions is a safe, quick, and accurate method. For diagnosing thoracic lesions, a single sample with an 18-G biopsy needle is sufficient to achieve a final diagnosis when using appropriate histologic methods.

Journal Article↗
PubMed2001

[Retrospective evaluation of surgically treated cases of non-palpable breast tumor].

Between 10.01.1997 and 09.30.1999 authors performed operations on 78 patients who had nonpalpable breast tumors. If mammography was considered abnormal during breast screening program patients were recalled. Besides clinical investigation complimentary mammograms were performed. After sonogram, and if needed, aspiration biopsy cytology (ABC) if necessary core biopsy (CB) was the next investigation. 79 operations were performed on 78 patients (one was patient had synchronous breast tumor). The mean age of the patients was 56.3 years. If the radiological investigations (R4-R5) and/or the ABC (C4-C5) or CB suggested malignancy operation was performed. Mammography suggested malignancy in 60.75% of the patients, it was suggested by ABC in 30.18%, and by CB in 55.5%. The nonpalpable tumor, suspected to be malignant was marked with a wire loop and was excised under anesthesia along with the affected breast sector. The excision and tissue-border around the tumor was checked by specimen mammography performed during the narcosis. No cryohistology was performed. After the specimen mammography, the wound was closed. The final histology of the operations showed malignancy in 40.5%. In their retrospective study the authors evaluated the complete sensitivity and the positive predictive value (PPV) of the preoperative investigations regarding the final histology. They analyse the value of preoperative mammogram, the ABC and CB in malignant and in benign cases. Early diagnosis and surgical treatment is expected to improve significantly the survival of patients with breast cancer. Reduction in the number of unnecessary operations can be expected from increasing the accuracy of radiological and cytological investigations and the adequate usage of core biopsy.

Biopsy, Needle↗
PubMed2001

[Nipple transposition on superomedial pedicle in reduction mammoplasties].

BACKGROUND: Transposing the nipple-areola complex is a challenge at reduction mammaplasties, particularly when the distance between the sites is big and great amount of breast tissue has to be removed. Many techniques are used, all have to fulfill the following conditions: the blood supply and sensation of the nipple have to be preserved and closure must be tension-free. OBJECTIVE: To evaluate how the superomedial pedicle for nipple transposition fulfills the above requirements. METHOD: Fifteen reduction mammaplasties performed in this way (resection weight: 435 g/breast), postoperative patient examinations with emphasis on sensation. RESULTS: Nipple viability was good without necrosis, retaining sensation was also good with no loss of sensation. CONCLUSION: The technique is safe, giving good cosmetic results.

Adult↗
PubMed2000

Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase.

Hemorrhagic shock (HS) and resuscitation leads to widespread production of oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various disease conditions associated with oxidative stress. We tested the hypothesis whether PARP activation plays a role in the multiple organ dysfunction complicating HS and resuscitation in a murine model of HS and resuscitation by using mice genetically deficient in PARP (PARP(-/-)) and their wild-type littermates (PARP(+/+)). Animals were bled to a mean blood pressure of 45 mmHg (1 mmHg = 133 Pa) and resuscitated after 45 min with isotonic saline (2x volume of shed blood). There was a massive activation of PARP, detected by poly(ADP-ribose) immunohistochemistry, which localized to the areas of the most severe intestinal injury, i.e., the necrotic epithelial cells at the tip of the intestinal villi, and colocalized with tyrosine nitration, an index of peroxynitrite generation. Intestinal PARP activation resulted in gut hyperpermeability, which developed in PARP(+/+) but not PARP(-/-) mice. PARP(-/-) mice were also protected from the rapid decrease in blood pressure after resuscitation and showed an increased survival time, as well as reduced lung neutrophil sequestration. The beneficial effects of PARP suppression were not related to a modulation of the NO pathway nor to a modulation of signaling through IL-6, which similarly increased in both PARP(+/+) and PARP(-/-) mice exposed to HS. We propose that PARP activation and associated cell injury (necrosis) plays a crucial role in the intestinal injury, cardiovascular failure, and multiple organ damage associated with resuscitated HS.

Acetylcholine↗
PubMed2000

Development of a sensitive ELISA for the determination of fumonisin B(1) in cereals.

Monoclonal fumonisin B(1) antibodies with high titer were raised by using FB(1)-glutaraldehyde-keyhole limpet hemocyanin immunogen prepared by a short cross-linker reagent (glutaraldehyde). Mean cross-reactivities of the selected monoclonal antibody for FB(1), FB(2), and FB(3) were 100, 91.8, and 209%, respectively; no reactivity was found with hydrolyzed fumonisin. A direct, competitive enzyme-linked immunosorbent assay for the quantitative determination of FB(1) in cereals has been developed with this antibody. Fifty percent acetonitrile-based solvent with some additives was used for extraction of cereals, and the diluted extracts were used without cleanup in the test. The mean within-assay and interassay coefficients of variation for the standard curve were <10%. The measuring range of this test is 10-500 ng/g, with a detection limit of 7.6 ng/g FB(1). The toxin recovery from cereals infected with 50-200 ng/g of FB(1) varied between 61 and 84%. According to the comparable results of naturally infected maize samples, this test proved to be suitable for the rapid screening of food and feed samples for the presence of FBs.

Carboxylic Acids↗
PubMed2000

Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism.

Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proliferation of parathyroid cells. Vitamin D deficiency and reduced parathyroid VDR expression has been associated with development of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger RNA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR mRNA relative to glyceraldehyde-3-phosphate dehydrogenase mRNA levels were determined by RNase protection assay in 42 single parathyroid adenomas of patients with primary HPT, 23 hyperplastic glands of eight patients with uremic HPT, and 15 normal human parathyroid glands. The adenomas and hyperplasias demonstrated similar VDR mRNA levels, which were reduced (42 +/- 2.8% and 44 +/- 4.0%) compared with the normal glands (P < 0.0001). Comparison of parathyroid adenoma with a normal-sized parathyroid gland of the same individual (n = 3 pairs) showed a 20-58% reduction in the tumor. Nodularly enlarged glands represent a more advanced form of secondary HPT and showed greater reduction in the VDR mRNA levels than the diffusely enlarged glands (P < 0.005). The reduced VDR expression is likely to impair the 1,25(OH)2D3-mediated control of parathyroid functions, and to be of importance for the pathogenesis of not only uremic but also primary HPT. Circulating factors like calcium, PTH, and 1,25(OH)2D3 seem to be less likely candidates mediating the decreased VDR gene expression in HPT.

Adenoma↗
PubMed1999

[Radiologic follow-up after breast-conserving surgery: value of MRI examination of the breast].

The aim of the study was to establish an objective method for evaluation the extent, topography and quantity of skin and soft tissue side effects after tele- and/or brachyradiotherapy of the conserved breast and to compare the sequales of different radiation methods. 26 patients operated on for T1-2 N0-1 breast cancer underwent the following kinds of postoperative radiotherapy: 1. 46-50 Gy whole breast teletherapy + 10-16 Gy electron boost (5 patients), 2. 46-50 Gy teletherapy + 10-15 Gy HDR brachytherapy boost (12 patients), 3. 46-50 Gy teletherapy (6 patients), 4. 36,4 Gy sole HDR brachytherapy of the tumour bed (5 patients). The postirradiation side effects were examined by MRI, mammogram, US and physical examination, as well. MRI was performed on a 0.5 T, double breast coil, with SE-T1, SE-T2 and 3D-GE sequences. The findings of MRI and mammography were compared to physically detectable side effects using the RTOG/EORTC late radiation morbidity scoring scheme. US is useful in the measurement of skin thickening and in the diagnosis of fat necrosis. Mammography and physical examination are very subjective and low specificity methods to evaluate postirradiation side effects. MRI is a suitable and more objective method to detect the real extent and quantity of skin thickening and fibrosis. The incidence of > or = G2 side effects of skin and breast parenchyma were 64.5 and 32.2%, respectively. The differences between the side effects of whole breast irradiation and sole brachytherapy of the tumour bed are also clearly demonstrated. Brachytherapy alone is feasible without compromising cosmetic results. The authors established the MRI criteria for categorization the extent and grade of skin thickening and fibrosis (focal vs diffuse, grade 1-4). Breast MRI is an objective tool for assisting to the evaluation of the side effects of postoperative radiotherapy.

Brachytherapy↗
PubMed1999

[Risk assessment and measuring the need for revascularization on the basis of residual ischemia by means of dobutamine stress echocardiography in the early phase of the first myocardial infarction].

The aim of this study is to present a modern method which can be used in the early phase of myocardial infarction. Its results show that with the detection of residual ischaemia, valuable information can be gained concerning the progression of the disease and the claim to revascularisation. During the first week (2-7 days), the authors performed risk assessing dobutamine stress echocardiography in 52 nonselected acute patients with first myocardial infarction. Patients with negative results were regarded as low risk cases 35/52 (67.3%), while those with positive results were regarded as high risk cases 17/52 (32.7%). The number of the serious postinfarction hard events was 22/52 (42.3%) during the one-year following period. In the case of the positive group, during mainly the first three months the occurrence of such events was found to be extremely high: 16/17 (94.1%), while in the case of the negative group it was only 6/35 (17.1%). On the basis of the test results it can be stated that coronarography was performed in 14/17 (82.4%) vs. 3/35 (8.6%) of the cases, and revascularisation in 10/17 (58.8%) vs. 1/35 (2.9%) of the cases. In 2/17 (11.8%) vs. 3/35 (8.6%) of the cases, the patients suffered from acute coronary syndrome and the mortality rate was 2/17 (11.8%) vs. 1/35 (2.9%). The sensitivity value was 79.1%, the specificity value 90.6%, and the positive and negative predictive values 86.3% and 85.3%. There was no such significant complication detected which could be attributable to the examination. On the basis of the results and corresponding to the data in special literature, the authors found the dobutamine stress test a good and safe prognostical method even some days after the infarction. With the help of this method the high and low risk groups of patients can be separated early, and at the same time the claim to revascularisation in the first three months can be measured too.

Acute Disease↗
PubMed1999

Analysis of serum and seminal plasma after feeding ochratoxin A with breeding boars.

The aim of the experiment was to investigate whether or not ochratoxin A (OA) can be detected in seminal plasma after feeding the toxin in five and 10 times of the human tolerable daily intake with breeding boars and how toxin profiles of serum and seminal plasma correspond to each other. In addition to that, the effect of the toxin challenge on motility and longevity of boar semen was also evaluated. OA from samples was analyzed by microplate ELISA. Percentage of progressive motility of spermatozoa was determined initially and after 24, 48, 96, 120 and 144 h of storage. OA appeared in serum and seminal plasma shortly after toxin application had started. Significant reduction of initial motility and impaired longevity was observed after toxin withdrawal. These findings suggest that OA might have the potential to affect sperm production and semen quality of boars, but further research is required to elucidate whether OA exerts direct effect on germinal epithelium or disturbs sperm cell maturation only.

Animals↗