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Elevated Birth Rates in CD62L (L-Selectin)-Deficient BALB/c Mice: Potential Involvement of NK Cells

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Open Journal of Immunology 2014年第4期4卷 148-156页

作者： Balint Farkas Jozsef Bodis Aaron R. Mangold Adrienn Angyal Ferenc Boldizsar katalin Mikecz Tibor T. Glant Department of Obstetrics and Gynecology University of Pecs Clinical Center Pécs Hungary Section of Molecular Medicine Department of Orthopedic Surgery Biochemistry Internal Medicine (Section of Rheumatology) at Rush University Medical Center Chicago USA Janos Szentagothai Research Centre University of Pecs Pécs Hungary Department of Dermatology Mayo Clinic Scottsdale USA Department of Cardiovascular Science University of Sheffield Sheffield UK Department of Immunology and Biotechnology University of Pecs Pécs Hungary

Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.

关键词： L-Selectin Pregnancy BALB/c CD62L NK Cells Lymphocyte Homing

Pedigree and genetic analysis of a novel mutation carrier patient suffering from hereditary nonpolyposis colorectal cancer

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World Journal of Gastroenterology 2006年第8期12卷 1192-1197页

作者： Miklós Tanyi Judith Olasz Géza Lukács Orsolya Csuka László Tóth Zoltán Szentirmay Zsuzsa Ress Zsolt barta János L Tanyi László Damjanovich 1~(st)Department of Surgery University of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of Pathogenetics National Institute of OncologyBudapestHungary Department of Pathology University of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of Human and Experimental Tumor Pathology National Institute of OncologyBudapestHungary 3~(rd)Department of Medicine University of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of Obstetrics and Gynecology Baylor College of MedicineHoustonTXUnited States

AIM： To screen a suspected Hungarian HNPCC family to find specific mutations and to evaluate their effect on the presentation of the disease. METHODS： The family was identified by applying the Amsterdam and Bethesda Criteria. Immunohistochemistry was performed, and DNA samples isolated from tumor tissue were evaluated for microsatellite instability. The identification of possible mutations was carried out by sequencing the hMLH1 and hMSH2 genes. RESULTS： Two different mutations were observed in the index patient and in his family members. The first mutation was located in exon 7, codon 422 of hMSH2, and caused a change from Glu to STOP codon. No other report of such a mutation has been published, as far as we could find in the international databases. The second mutation was found in exon 3 codon 127 of the hMSH2 gene, resulting in Asp→Ser substitution. The second mutation was already published, as a non-pathogenic allelic variation. CONCLUSION： The pedigree analysis suggested that the newly detected nonsense mutation in exon 7 of the hMSH2 gene might be responsible for the development of colon cancers. In family members where the exon 7 mutation is not coupled with this missense mutation, colon cancer appears after the age of 40. The association of these two mutations seems to decrease the age of manifestation of the disease into the early thirties.

关键词： Hereditary nonpolyposis colon cancer Bethesda criteria Mutation hMLH1 hMSH2

Screening potential genotoxic effect of aquatic plant extracts using the mussel micronucleus test

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Journal of Coastal Life Medicine 2016年第1期 36-38页

作者： Bettina Eck-Varanka Nora Kováts katalin Hubai Gábor Paulovits Árpád Ferincz Eszter Horváth Department of Limnology University of PannoniaVeszprémHungary Balaton Limnological Institute Centre for Ecological ResearchHungarian Academy of SciencesBudapestHungary Department of Aquaculture Szent István UniversityGödöllőHungary

Objective:To assess the genotoxic potential of selected aquatic macrophytes:Ceratophyllum demersum L.(hornwort,family Ceratophyllaceae),Typha angustifolia L.(narrowleaf cattail,family Typhaceae),Stratiotes aloides L.(water soldier,family Butomaceae),and Oenanthe aquatica(L.)Poir.(water dropwort,family Umbelliferae).Methods:For genotoxicity assessment,the mussel micronucleus test was *** frequency was determined from the haemolymph of Unio pictorum L.(painter’s mussel).In parallel,total and hydrolisable tannin contents were ***:All plant extracts elucidated significant mutagenic *** correlation was determined between tannin content and mutagenic ***:The significant correlation between genotoxicity as expressed by micronucleus frequency and tannin content(both total and hydrolisable tannins)indicate that tannin is amongst the main compounds being responsible for the genotoxic *** might be suggested that genotoxic capacity of these plants elucidate a real ecological effect in the ecosystem.

关键词： Genotoxicity Mussel micronucleus test Unio pictorum Tannin

Vitamin D and autoimmune thyroid diseases

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Cellular & Molecular Immunology 2011年第3期8卷 243-247页

作者： Shaye Kivity Nancy Agmon-Levin Michael Zisappl Yinon Shapira Endre V Nagy katalin Danko Zoltan Szekanecz Pnina Langevitz Yehuda Shoenfeld The Zabludovicz Center for Autoimmune Diseases Sheba Medical CenterTel-Hashomeraffiliated to Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Medicine‘A&C’ Sheba Medical CenterTel-HashomerIsrael Rheumatic Disease Unit Sheba Medical CenterTel-HashomerIsrael Department of Medicine‘B’ Sheba Medical CenterTel-HashomerIsrael University of Debrecen.Medical and Health Science Center DebrecenHungary Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases Tel Aviv UniversityTel AvivIsrael

The role of vitamin D as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus *** D mediates its effect though binding to vitamin D receptor(VDR),and activation of VDR-responsive *** VDR gene polymorphism was found to associate with autoimmune thyroid diseases(AITDs),few studies examined levels of vitamin D in these patients and those that did yielded conflicting *** therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy *** vitamin D(25-OH)levels were measured in 50 patients with AITDs,42 patients with non-AITDs and 98 healthy subjects,utilizing the LIAISON chemiluminescence immunoassay(DiaSorin,Saluggia,Italy).VitaminD deficiency was designated at levels lower than 10 ng/*** antibodies,thyroid functions and demographic parameters were evaluated in all *** prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals(72% versus 30.6%;P<0.001),as well as in patients with Hashimoto’s thyroiditis compared to patients with non-AITDs(79% versus 52%;P<0.05).Vitamin D deficiency also correlated to the presence of antithyroid antibodies(P=0.01)and abnormal thyroid function tests(P=0.059).Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests,suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

关键词： autoantibodies autoimmune thyroid disease Graves’disease Hashimoto’s thyroiditis vitamin D

Microscopic colitis: A retrospective study of clinical presentation in 53 patients

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World Journal of Gastroenterology 2005年第9期11卷 1351-1355页

作者： Zsolt barta Gabriella Mekkel István Csíp(o|") László Tóth Szabolcs Szakáll Gábor G.Szabó Gyula Bakó Gyula Szegedi Margit Zeher Third Department of Medicine Department of Pathology

AIM: To evaluate the relationship between symptoms and microscopic colitis (MC) subtypes: to test whether collagenous colitis (CC) and/or lymphocytic colitis (LC)might be related to both constipation and ***: A cohort of patients with independently confirmed typical histopathological changes was investigated. Fifty-three patients with histologically proved MC (46 with CC, 7 with LC) were included. The existence of diarrhea or constipation and the co-existence of autoimmune diseases were also investigated and all data were retrospectively ***: Twenty-three (43.39%) of MC patients had chronic constipation (20 in CC, 3 in LC patients). Twentyfour(45.28%) of MC patients had autoimmune disease and the diagnosis of autoimmune disease was always prior to MC. Sjogren's syndrome was associated only with the constipation ***: The Janus face of MC resembles the subgroups of irritable bowel syndrome. The co-existence of autoimmune diseases and MC is confirmed in both the constipation and diarrhea subgroups.

关键词： Microscopic colitis Constipation Autoimmune

Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease

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World Journal of Gastroenterology 2006年第34期12卷 5550-5553页

作者： Judit Bene Lili Magyari Gábor Talián katalin Komlósi Beáta Gasztonyi Beáta Tari gnes Várkonyi Gyula Mózsik Béla Melegh MTA PTE Clinical Genetics Research Group of Hungarian Academy of Sciences at the University of Pécs Pécs Hungary Department of Medical Genetics and Child Development University of Pécs Pécs Hungary Department of Medical Genetics and Child Development University of Pécs Pécs Hungary 1~(st) Department of Medicine School of Medicine University of Pécs Pécs Hungary Department of Pediatrics and Child Health Center University of Szeged Szeged Hungary

AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METHODS： A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn＇s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants （Arg702Trp, Gly908Arg and 2007finsC changes） with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specific regions of these genes. RESULTS： At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profile was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls （9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls）. No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION： The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.

关键词： OCTN1 OCTN2 NOD2/CARD15 Crohn's disease

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

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World Journal of Gastroenterology 2007年第15期13卷 2205-2208页

作者： Lili Magyari Bernadett Faragó Judit Bene katalin Horvatovich Lilla Lakner Márta Varga Mária Figler Beáta Gasztonyi Gyula Mózsik Béla Melegh Department of Medical Genetics and Child Development University of Pécs PécsHungary MTA PTE Clinical Genetics Research Group of the Hungarian Academy of Sciences at the University of Pécs Pécs Hungary Markusovszky Hospital Department of Medicine and Gastroenterology SzombathelyHungary Réthy Pál Hospital 3rd Department of Medicine and Gastroenterology BékéscsabaHungary Department of Medicine School of Medicine University of PécsPécsHungary Department of Gastroenterology Zala County Hospital ZalaegerszegHungary

AIM： The goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene （CTLA4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）. METHODS： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （SNP）. The genotypes were determined by using PCR/RFLP test. RESULTS： The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION： The results of the current study show that carriage of the ＋49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

关键词： Cytotoxic T-lymphocyte antigen 4 Crohn's disease Ulcerative colitis Inflammatory bowel disease

Foreign body impaction in the sigmoid colon: A twenty euro bet

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World Journal of Gastroenterology 2013年第24期19卷 3892-3894页

作者： katalin E Müller András Arató Péter László Lakatos Mária Papp Gábor Veres 1~(st) Department of Pediatrics Semmelweis University1083 Budapest Hungary 1~(st) Department of Pediatrics Semmelweis University 1~(st) Department of Medicine Semmelweis University1083 Budapest Hungary 2~(nd) Department of Medicine University of Debrecen4032 Debrecen Hungary

Foreign body ingestion is a common clinical problem in early childhood. However, it may occur even in adults, unknowingly. Most ingested foreign bodies entering the stomach pass through the gastrointestinal tract uneventfully. Here we report on a 13-year-old boy who presented with chronic abdominal pain, weight loss and occult gastrointestinal bleeding for 6 mo. Colonoscopy was negative; however, a ballpoint pen was impacted in the sigmoid region. Subsequently, the child admitted swallowing a pen as a 20-euro bet 6 mo previously. Crohn's disease is a chronic relaps-ing inflammatory gastrointestinal disease. It is often difficult to diagnose due to the fact that there is no single pathognomonic sign or symptom. This case is a description of an adolescent with chronic gastrointes-tinal symptoms due to a foreign body. Therefore, an ingested foreign body should be included in the differ-ential diagnostic procedure related to gastrointestinal symptoms.

关键词： Foreign bodies Pen Differential diagnosis Crohn’s disease Child

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

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World Journal of Gastroenterology 2006年第2期12卷 251-258页

作者： Annamaria Szabolcs Russel J Reiter Tamas Letoha Peter Hegyi Gabor Papai Ilona Varga katalin Jarmay Jozsef Kaszaki Reka Sari Zoltan Rakonczay Jr Janos Lonovics Tamas Takacs st Department of Medicine University of SzegedHungary Department of Cellular and Structural Biology University of TexasHealth Science CentreSan AntonioTexasUnited States Institute of Chemistry University of SzegedHungary Biological Research Centre Hungarian Academy of SciencesSzegedHungary Biological Isotope Laboratory University of SzegedHungary Institute of Experimental Surgery University of SzegedHungary

AIM： To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine （L-Arg） -induced experimental pancreatitis in rats. METHODS： Male Wistar rats （25） were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS： L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio （pw/bw）, the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes （Cu/Zn-superoxide dismutase （CulZn-SOD） and catalase （CAT）） were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION： Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

关键词： Acute pancreatitis Melatonin Scavengers