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Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

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World journal of Gastroenterology 2008年第27期14卷 4342-4346页

作者： Ferenc Nagy Tamás Molnár Zoltán Szepes Klaudia Farkas Tibor Nyári jános Lonovics First Department of Medicine University of Szeged Faculty of Medicine Institute of Medical Informatics University of Szeged Faculty of Medicine

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.

关键词： Inflammatory bowel disease Azathioprine 6-mercaptopurine Side effects Efficacy

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八十年代的匈牙利农业

世界农业 1985年第9期 8-9页

作者： jànos Marton

15世纪末,匈牙利的种植业和畜牧业即发展到了相当高的水平。当时,匈牙利人民的营养标准高于欧洲的平均水平,而且有了相当数量的谷物、肉牛和葡萄酒出口。进入16世纪后,历经五百多年反对外族压迫的连绵不断的战争,使匈牙利农业遭到了破... 详细信息

15世纪末,匈牙利的种植业和畜牧业即发展到了相当高的水平。当时,匈牙利人民的营养标准高于欧洲的平均水平,而且有了相当数量的谷物、肉牛和葡萄酒出口。进入16世纪后,历经五百多年反对外族压迫的连绵不断的战争,使匈牙利农业遭到了破坏。尽管如此,已达到欧洲平均水平的匈牙利农业,在第二次世界大战以前仍然得

关键词：农业平均欧洲国营农场合作社经济组织匈牙利八十年代

Stress Analysis of Bolted joints Part II. Contact and Slip Analysis of a Four Bolt joint

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Modern Mechanical Engineering 2014年第1期4卷 46-55页

作者： László Molnár Károly Váradi jános Holubán Andor Tamási Department of Machine and Product Design Budapest University of Technology and Economics Budapest Hungary

For up-to-date bolted joints, first of all in vehicles, high strength bolts of 10.9 or even 12.9 are used, which are preloaded up to 90% or even 100% of the yield strength. The primary aim of this high degree utilization is the weight reduction. For the analytic dimensioning of bolted joints, the VDI 2230 Richtlinien German standard [1] provides support. However, the analytic model can mostly consider the true structural characteristics only in a limited way. The analytic modeling is especially uncertain in case of multiple bolted joints when the load distribution among the bolts depends reasonably upon the elastic deformation of the participating elements in the joints over the geometry of the bolted joint. The first part of this paper deals with the problems of numerical modeling and stress analysis, respectively specifying the analytic dimensioning procedure by applying elastic or rather elastic-plastic material law. The error magnitude in bolted joint calculation was examined in case of omitting the existing threaded connection—between the bolt and the nut—in order to simplify the model. The second part of the paper deals with the dimensioning of stands and cantilevers’ multi-bolt fixing problems, first of all, with the load distribution among the bolts keeping in view the analysis of the local slipping relations. For demonstrating the above technique, an elaborated numeric procedure is presented for a four-bolted cantilever, having bolted joints pre-tightened to the yield strength.

关键词： Bolted joints Numerical Modeling Stress Analysis

Alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma

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World journal of Gastroenterology 2005年第32期11卷 5015-5018页

作者： Dénes Grg jános Regly-Mérei Sándor Paku László Kopper Péter Nagy Department of Transplantation and SurgerySemmelweis University BudapestHungary Third Department of SurgerySemmelweis University BudapestHungary joint Research Organization of the Hungarian Academy of Sciences and Semmelweis UniversityBudapest Hungary First Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestHungary

AIM： To characterize the alpha-fetoprotein （AFP） positive and negative hepatocellular carcinoma （HCC） samples. METHODS： Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens： AFP,β-catenin, p53, CD44, MSH-2, MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups. RESULTS： Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nudear p53 staining were AFP positive, while seven tumors with nuclear β-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and dinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples. CONCLUSION： AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear β-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data on in vivo human tumors.

关键词： Hepatocellular carcinoma Alpha-fetoprotein p53 β-catenin CD44

Solubilization and purification of recombinant modified C-reactive protein from inclusion bodies using reversible anhydride modification

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Biophysics Reports 2015年第1期1卷 18-33页

作者： Lawrence A.Potempa Zhen-Yu Yao Shang-Rong ji jános G.Filep Yi Wu Roosevelt University College of Pharmacy MOE Key Laboratory of Cell Activities and Stress Adaptations School of Life SciencesLanzhou University Research Center Maisonneuve-Rosemont HospitalUniversity of Montreál Key Laboratory of Preclinical Study for New Drugs of Gansu Province Lanzhou University

The precise function of C-reactive protein(CRP) as a regulator of inflammation in health and disease continues to evolve. The true understanding of its role in host defense responses has been hampered by numerous reports of comparable systems with contradictory interpretations of CRP as a stimulator, suppressor, or benign contributor to such processes. These discrepancies may be explained in part by the existence of a naturally occurring CRP isoform, termed modified CRP(i.e., m CRP), that is expressed when CRP subunits are dissociated into monomeric structures. The free m CRP subunit undergoes a non-proteolytic conformational change that has unique solubility, antigenicity, and bioactivity compared to the subunits that remain associated in the native, pentameric CRP molecule(i.e., p CRP). As specific reagents have been developed to identify and quantify m CRP, it has become apparent that this isoform can be formed spontaneously in calcium-free solutions. Furthermore, m CRP can be expressed on perturbed cell membranes with as little as 24–48 h incubation in tissue culture. Because m CRP has the same size as p CRP subunits as evaluated by SDS-PAGE, its presence in a p CRP reagent would not be apparent using this technique to evaluate purity. Finally, because many antibody reagents purported to be specific for ‘‘CRP’contains some, or substantial specificity to m CRP, antigen-detection techniques using such reagents may fail to distinguish the specific CRP isoform detected. All these caveats concerning CRP structures and measurements suggest that the aforementioned contradictory studies may reflect to some extent on distinctive bioactivities of m CRP rather than on p CRP. To provide a reliable, abundant supply of m CRP for separate and comparable studies, a recombinant protein was engineered and expressed in E. coli(i.e., recombinant m CRP or rmCRP). Synthesized protein was produced as inclusion bodies which proved difficult to solubilize for purification and characteri

关键词： Recombinant modified C-reactive protein Inclusion bodies Citraconic anhydride

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不打折扣的光学集成

世界电子元器件 2020年第10期 11-15页

作者： jános Pálhalmi Data Sense Labs Ltd. jan-Hein Broeders ADI公司

光电容积脉搏波(PPG)是测量血氧饱和度(SPO2)水平的常用技术。使用光发射器向人体发射光,然后使用光接收器测量反射或未吸收的光的数量。根据两段波长的比值,可以测量氧合血红蛋白的数量。类似技术也被用于测量心率(结合光学技术)或心... 详细信息

光电容积脉搏波(PPG)是测量血氧饱和度(SPO2)水平的常用技术。使用光发射器向人体发射光,然后使用光接收器测量反射或未吸收的光的数量。根据两段波长的比值,可以测量氧合血红蛋白的数量。类似技术也被用于测量心率(结合光学技术)或心率变异性。所有这些系统都需要使用一个或多个光发射器(需要控制),以及一个光电探测器来测量光电流量,由此测量接收到的光量。这个接收信号最终需要放大、调节,并数字化。听起来这种光学系统似乎非常简单;但是,在缺少光学知识的情况下,很容易检索到与用户寻找的信号毫不相关的光学信号。

关键词：光发射器光接收器光电探测器光学集成氧合血红蛋白心率变异性光学信号 SPO2

Methionine sources and genotype affect embryonic intestinal development,antioxidants,tight junctions,and growth-related gene expression in chickens

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Animal Nutrition 2024年第1期16卷 218-230页

作者： james K.Lugata Sawadi F.Ndunguru Gebrehaweria K.Reda Xénia E.Ozsváth Eszter Angyal Levente Czeglédi Gabriella Gulyás Renáta Knop jános Oláh Zoltán Mészár Rita Varga Brigitta Csernus Csaba Szabó Department of Animal Nutrition and Physiology Faculty of Agriculture and Food Sciences and Environmental ManagementUniversity of DebrecenDebrecenHungary Department of Animal Husbandry Faculty of Agriculture and Food Sciences and Environmental ManagementUniversity of DebrecenDebrecenHungary Faculty of Agriculture and Food Sciences and Environmental Management Doctoral School of Animal ScienceUniversity of DebrecenDebrecenHungary Institutes for Agricultural Research and Educational Farm University of DebrecenDebrecenHungary Department of Anatomy Histology and EmbryologyFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Evolutionary Zoology and Human Biology Faculty of Science and TechnologyUniversity of DebrecenDebrecenHungary

Methionine(Met)is an essential and first limiting amino acid in the poultry diet that plays a significant role in chicken embryonic development and *** present study examined the effect of in ovo injection of DL-Met and L-Met sources and genotypes on chicken embryonic-intestinal development and *** eggs of the two genotypes,TETRA-SL layer hybrid(TSL)—commercial layer hybrid and Hungarian Partridge colored hen breed(HPC)—a native genotype,were randomly distributed into four treatments for each *** treatment groups include the following:1)control non-injected eggs(NoIn);2)saline-injected(SaIn);3)DL-Met injected(DLM);and 4)L-Met injected(LM).The in ovo injection was carried out on 17.5 d of embryonic development;after hatching,eight chicks per group were sacrificed,and the jejunum was extracted for *** results showed that both DLM and LM groups had enhanced intestinal development as evidenced by increased villus width,villus height,and villus area(Pjection of Met enhanced intestinal development,and function,with genotypes responding differently under normal *** also influenced the expression of intestinal antioxidants,tight junction,and growth-related genes.

关键词： DL-Methionine L-Methionine In ovo injection Intestinal development Poultry

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Cardiopulmonary and hemodynamic changes in complement activation-related pseudoallergy

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Health 2013年第6期5卷 1032-1038页

作者： László Dézsi Gábor Szénási Rudolf Urbanics László Rosivall jános Szebeni Department of Community Medicine Faculty of Medical Sciences University of Sri Jayawardhanapura Nugegoda Sri Lanka Department of Languages and Cultural Studies University of Sri Jayawardhanapura Nugegoda Sri Lanka Institute of Pathophysiology Faculty of Medicine Semmelweis University Budapest Hungary Nanomedicine Research and Education Center Semmelweis University Budapest Hungary SeroScience Ltd. Budapest Hungary

Complement activation-related pseudoallergy (CARPA) is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. It is an acute infusion reaction dominated by cutaneous and hemodynamic changes, most significantly a cardiopulmonary distress involving major pulmonary hypertension, systemic hypotension and arrhythmias. Because CARPA is unpredictable by conventional allergy tests and it may be life threatening, it can represent a major barrier to the safe therapeutic application of many modern medicines, including liposomal drugs and monoclonal antibodies. This review summarizes and updates the facts and opens questions regarding this phenomenon, with particular focus on its porcine model.

关键词： CARPA Hypersensitivity Anaphylaxis Liposome Pig

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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