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Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

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World Journal of Gastroenterology 2005年第10期11卷 1489-1495页

作者： Peter Laszlo Lakatos Laszlo Lakatos Ferenc Szalay Claudia Willheim-Polli Christoph (O|¨)sterreicher Zsolt Tulassay tamas molnar Walter Reinisch Janos Papp Gyula Mozsik Hungarian IBD Study Group Peter Ferenci 1st Department of Medicine Laszlo Lakatos Department of Internal Medicine 4 2nd Department of Medicine Semmelweis University 2nd Department of MedicineSemmelweis UniversityBudapest:Laszlo PronaiAnnamaria NemethPal Miheller Erzsebet Hospital 1st Department of MedicineBudapest: Agota KovacsLaszlo Bene Szent Janos Hospital 1st Department of Medicine:Gyorgy Szekely University of Pecs 1st Department of MedicinePecs:Beata Gasztonyi University of Szeged 1st Department of MedicineSzeged:Ferenc NagyJanos Lonovics Semmelweis Hospital 1st Department of MedicineMiskolc:Laszlo Ujszaszy University of Debrecen 2nd Department of MedicineDebrecen:Istvan AltorjaiKaroly Palatka Kenezi Gy. County Hospital 2nd Department of MedicineDebrecen: Gyula G. Kiss County Hospital 2nd Department of MedicineZalaegerszeg Ferenc Tarnok Markusovszky Hospital2nd Department of MedicineSzombathely:Zoltan Dobronte Csolnoky F. County Hospital 1st Department of MedicineVeszprem:Zsuzsanna ErdelyiTunde PandurGabor Mester

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

关键词： Crohn's disease NOD2 CARD15 TLR4 Extraintestinal manifestation Phenotype

A new device for the identification of lymph nodes removed during different types of neck dissection

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Health 2010年第9期2卷 1093-1096页

作者： Imre Gerlinger tamas Ferenc molnar tamas Jarai Peter Moricz Gabor Rath Gyula Gobel Department of Otorhinolaryngology&Head and Neck Surgery Medical SchoolUniversity of PecsPecsHungary Department of Otorhinolaryngology&Surgery Medical SchoolUniversity of PecsPecsHungary

Meticulous mapping of the lymph node status is a general principle in present-day head and neck surgery. The removal of a certain number of lymphatic levels during neck dissection may well be therapeutic in intent, but it is also mandatory for correct tumour staging. We pre- sent a precise lymph node mapping during dif- ferent types of neck dissection in the course of major head and neck surgery by a sterile plastic tray moulded in the shape of the neck. This de- vice makes lymph node mapping simpler, safer, quicker and methodically more structured than any of the present methods. It facilitates the work of the pathologist and the flow of reliable information along the surgeon-pathologist- oncologist chain. With this device, a more stru- ctured, methodical means of lymph node removal has become possible.

关键词： Head and Neck Surgery Lymph Node Mapping Neck Dissection

NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

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World Journal of Gastroenterology 2010年第41期16卷 5233-5240页

作者： Nora Meggyesi Lajos S Kiss Magdalena Koszarska Martin Bortlik Dana Duricova Laszlo Lakatos tamas molnar Martin Lenicek Libor Vítek Istvan Altorjay Maria Papp Zsolt Tulassay Pal Miheller Janos Papp Attila Tordai Hajnalka Andrikovics Milan Lukas Peter Laszlo Lakatos Department of Molecular Diagnostics Hun-garian National Blood Transfusion Service H-1113 BudapestHungary 1st Depart-ment of Medicine Semmelweis University H-1083 BudapestHungary IBD Clinicaland Research Centre ISCARE IVF and 1st Medical FacultyCharles University 170 04 Prague Czech Republic 1st Department of Medicine Csolnoky F.County Hospital H8200 Veszprem Hungary 1st Department of Medicine University ofSzeged H6720 Szeged Hungary Department of Biochemistry andLaboratory Diagnostics 1st Medical Faculty Charles Univer-sity 170 04 Prague Czech Republic 2nd Department of Medicine University of Debrecen H4032 Debrecen Hungary 2nd Department of Medicine Semmelweis University H1085 Budapest Hungary

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

关键词： Crohn’s disease Ulcerative colitis NKX2-3 Immunity-related GTPase family M ECM1 Genotype Phenotype Pharmacogenetics

Newly developed histological tray for the application of identifying exact lymph node dissections in uro-logical surgical oncology

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Health 2013年第10期5卷 1629-1633页

作者： Istvan Buzogany Laszlo Vaczi Zsolt Domjan Fariborz Bagheri Attila Kiss Alex Dakay tamas Ferenc molnar Department of Urology and Surgery Peterfy Sandor Hospital KRBKBudapestHungary Department of Urology Dubai HospitalDubaiUAE Petz Aladar Hospital MK Department of Thoracic SurgeryGyorHungary Operational Medicine Department University Medical School PecsPecsHugary

In any urologic cancer surgery, lymph node dissection and its processing play a significant role in staging and management of the patients. Accordingly, precise handling of the dissected lymph nodes is important for histopathological work-up. The authors have developed a lymph node plastic tray shaping the abdomen and pelvis in which the dissected lymph nodes are placed in its determined location. This can be applied for any urologic cancer surgery. The research was designed to test the usage of a new histological tray. The objective was to assess how helpful it was for the surgical team and in the pathological process. The newly developed lymph node tray has been applied in 150 urological cancer surgeries and its efficacy and outcome have been evaluated in all these cases by involved doctors and assistants. This new tray simplifies lymph node removing and identification (staging), making it safer and quicker in any uro-oncological surgery. It facilitates the work of the pathologist and the flow of reliable information along the surgeon—pathologist-oncologist team. With usage of the tray, lymph node dissections are more structured by methodical means compared to any of the present methods.

关键词： Lymph Node Dissection Urogenital Surgical Oncology TNM System Safety and Hazards Histological Tray

What Is the Personal Experience of IBD Patients about Their Anti-TNF-Alpha Therapy?

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Health 2017年第7期9卷 1007-1018页

作者： Agnes Milassin Mariann Rutka Agnes Anna Csontos Pal Miheller Karoly Palatka Monika Szucs Zoltan Szepes Anita Balint Renata Bor Anna Fabian Klaudia Farkas Ferenc Nagy tamas molnar First Department of Medicine University of SzegedSzegedHungary 2^(nd) Department of Medicine Semmelweis UniversityBudapestHungary 2^(nd) Department of Internal Medicine University of DebrecenDebrecenHungary Department of Medical Physics and Informatics University of SzegedSzegedHungary

AIM: To evaluate and compare the patients opinion on the two types of anti- TNF-α therapies in a Hungarian cohort of IBD patients. METHODS: This was a prospective, multicentre, questionnaire-based observational study carried out in three Hungarian tertiary centres. From April to September 2014, an anonymous questionnaire was distributed to patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD), who have received infliximab (IFX) and/or adalimumab (ADA). The survey focused on the preferences of the two anti-TNF-α therapies on the basis of the efficacy, the administration routes and the side effects. RESULTS: 292 IBD patients, 216 CD, 75 UC and 1 indeterminate colitis patient completed the questionnaire. The mean duration of biological therapy was 1.7 (1 - 7) years. IFX treated patients noticed improvement of symptoms at 4 - 5 weeks while ADA treated patients noticed at 5 - 6 weeks. There was no difference between the patients’ satisfaction regarding the types of anti-TNF-α therapy if they received both. However, subcutaneous administration was preferred by ADA-treated patients previously receiving IFX (p = 0.007) compared to intravenous route and they did not intend to change the mode of therapy (p = 0.040). 90% of the patients, receiving only IFX or ADA were satisfied with their present therapy. The majority of patients (186/292, 63.7%) would not switch therapy. 63 of 291, 22% of the patients reported to have some concern with biological therapy—the majority (32/63, 50.8%) due to fear from side effects. CONCLUSION: Generally, patients preferred and would not change the present anti-TNF-α therapy, however, subcutaneous administration was preferred among those patients who had have experience with both.

关键词： Patient’s Satisfaction Personal Experience Questionnaire Anti-TNF-Alpha Therapy Patient’s Preference

A possible objective test to detect benign paroxysmal positional vertigo. The role of the caloric and video-head impulse tests in the diagnosis

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Journal of Otology 2022年第1期17卷 46-49页

作者： Andras molnar Stefani Maihoub Laszlo tamas Agnes Szirmai Semmelweis University Department of Otolaryngology and Head and Neck SurgerySzigony u.36.H-1083BudapestHungary

Background:Benign paroxysmal positional vertigo(BPPV)is characterized by vertigo lasting from seconds to minutes,induced by head ***:Our study aimed to investigate the clinical significance of the caloric vestibular and video head-impulse tests(vHIT)diagnosing the ***:68 patients suffering from posterior canal BPPV(25 male,43 females,mean age±SD,54.5±13.2 years)and 56 patients with a normal functioning vestibular system as control were *** caloric test and vHIT was performed during the same medical *** paresis(CP%),gain(GA)and asymmetry(GA%)parameters were ***:The Dix-Hallpike manoeuvre was only positive in 4%of this *** CP%parameter was only pathologic in two patients,and there was no significant difference between control and BPPV patients(p=0.76).The GA value was never under 0.8 in this population,but GA%was abnormal in 63.2%.A significant difference comparing the GA%values to the control group was seen(p=0.034).There was no correlation detected between the CP%and GA%values in *** the GA%value,61%sensitivity and 76%specificity was ***:The Dix-Hallpike manoeuvre was not often positive in the non-acute phase of BPPV;therefore,objective testing is *** caloric test does not have clinical significance in BPPV,but vHIT can be helpful based on the GA%parameter。

关键词： Caloric test Video-head-impulse test Benign paroxysmal positional vertigo Objective diagnosis

The diagnosis of central vestibular disorders based on the complementary examination of the vestibulospinal reflex

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Journal of Otology 2022年第1期17卷 1-4页

作者： Stefani Maihoub Andras molnar Laszl tamas Agnes Szirmai Department of Otorhinolaryngology and Head and Neck Surgery Faculty of MedicineSemmelweis UniversityBudapestHungary

Objectives:Stance and gait unsteadiness along with vertigo contribute to a central vestibular *** objective analysis ultrasound-computer-craniocorpography(US-COMP-CCG)can be *** of the study was to characterize the unsteadiness in central vestibular disorders and discuss the possible diagnostic usage of *** and results:Hundred-and-ninety patients(70 male and 120 female,mean age±SD,58.94±15.27)suffering from central vestibular disorder and 230 healthy control patients(78 male and 152 female,mean age±SD,50.94±15.27)were *** and gait analysis was according to vestibulospinal tests of *** SPSS V24 software was used for statistical ***-Whitney U test and Chi-square test were used,along with sensitivity and specificity *** significance level was p<*** to schematic and statistical analysis instability and postural sway were increased in the vertigo population and statistically significant difference was *** categorical analysis significant correlation was detected[standing test:longitudinal sway(p<0.00001),lateral sway(p<0.00001),forehead covering area parameters(p=0.0001);stepping test:longitudinal deviation(p=0.05),lateral sway(p=0.011)parameters].Conclusions:Clinicians should consider that postural instability is prominently present in this population and might be of a diagnostic importance.

关键词： Unsteadiness Central vestibular disorder Vestibulospinal reflex Ultrasound-computer-craniocorpography

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Short RNAs in Tomato

Journal of Integrative Plant Biology 2010年第4期52卷 388-392页

作者： tamas Dalmay School of Biological Sciences University of East Anglia

Short RNAs are 20-24 nucleotide long non-coding RNA molecules generated by one of the Dicer-like enzymes. They recognize specific RNA or DNA sequences and guide the RNA silencing complex to their targets leading to post-transcriptional or transcriptional gene silencing of the target. Most of our knowledge about short RNAs comes from studying the model species Arabidopsis. Recently, however, several reports emerged about short RNAs in tomato, which is a model plant for fleshy fruit development and ripening. Tomato short RNAs have been sequenced and a database was established. Novel non-conserved microRNAs were found that showed differential expression between fruit and other tissues, even during fruit development, suggesting that they may play a role in fruit formation. Several target genes were predicted and validated for both conserved and non-conserved miRNAs and some of these targets are key players in fruit ripening, such as Colourless non-ripening. The present study reviews the current state of tomato short RNAs research and suggests future directions.

关键词： Short RNAs in Tomato DCL RNA siRNAs

Global optimum of microstructure parameters in the CMWP line-profile-analysis method by combining Marquardt-Levenberg and Monte-Carlo procedures

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Journal of Materials Science & Technology 2019年第7期35卷 1508-1514页

作者： Gabor Ribarik Bertalan Joni tamas Ungar Department of Materials Physics Edtvos University BudapestPO Box 32H-15J8Hungary School of Materials The University of ManchesterM139PLUK

Line profile analysis of X-ray and neutron diffraction patterns is a powerful tool for determining the microstructure of crystalline materials. The Convolutional-Multiple-Whole-Profile (CMWP) procedure is based on physical profile functions for dislocations, domain size, stacking faults and twin boundaries. Order dependence, strain anisotropy, hkl dependent broadening of planar defects and peak shape are used to separate the effect of different lattice defect types. The Marquardt-Levenberg (ML) numerical optimiza-tion procedure has been used successfully to determine crystal defect types and densities. However, in more complex cases like hexagonal materials or multiple phases the ML procedure alone reveals uncer-tainties. In a new approach the ML and a Monte-Carlo statistical method are combined in an alternative manner. The new CMWP procedure eliminates uncertainties and provides globally optimized parameters.

关键词： X-ray line profile analysis Neutron line profile analysis CMWP Global optimum Dislocation densities Grain size Planar defects Monte-Carlo method